WorldWideScience

Sample records for international drug regulatory

  1. The value and benefits of the International Conference on Harmonisation to drug regulatory authorities: advancing harmonization for better public health.

    Science.gov (United States)

    Molzon, J A; Giaquinto, A; Lindstrom, L; Tominaga, T; Ward, M; Doerr, P; Hunt, L; Rago, L

    2011-04-01

    The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region. As more countries embrace ICH guidelines, we anticipate additional benefits, including the promotion of good review practices and, ultimately, a common regulatory language that will facilitate further interactions among global drug regulatory authorities.

  2. Orphan drugs: the regulatory environment.

    Science.gov (United States)

    Franco, Pedro

    2013-02-01

    The definition of a rare disease is not universal and depends on the legislation and policies adopted by each region or country. The main objective of this article is to describe and discuss the legal framework and the regulatory environment of orphan drugs worldwide. Some reflections and discussions on the need for specific orphan drug legislation or policies are described at length. Furthermore, some aspects of the history of each region in respect of the orphan drug legislation evolution are outlined. This article describes and compares the orphan drug legislation or policies of the following countries or regions: United Sates of America (US), European Union (EU), Japan, Australia, Singapore, Taiwan and Canada. The incentives described in the orphan drug legislations or policies, the criteria for designation of orphan status and the authorisation process of an orphan drug are also described and compared. The legislations and policies are to some extent similar but not the same. It is important to understand the main differences among all available legislative systems to improve the international collaboration in the field of orphan drugs and rare diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    In this last part is reviewed international regulatory activities and bilateral agreements including two parts: concerning European atomic energy community with European commission proposal for a council directive setting up a community framework for nuclear safety, update of the nuclear illustrative programme in the context of the second strategic energy review, european commission recommendation on criteria for the export of radioactive waste and spent fuel to third countries and a communication on nuclear non-proliferation and the second part in relation with international atomic energy agency with a joint convention on the safety of spent fuel management and on safety of radioactive waste management (third review meeting). (N.C.)

  4. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2002-01-01

    Different international regulatory activities are presented: recommendation on the protection of the public against exposure to radon in drinking water supplies, amendment to the legislation implementing the regulation on imports of agricultural products originating in third countries following the Chernobyl accident, resolution on the commission green paper towards a European strategy for the security of energy supply, declaration of mandatory nature of the international code for the safe carriage of packaged irradiated nuclear fuel, plutonium and high level radioactive wastes on board ships, adoption of action plan against nuclear terrorism. (N.C.)

  5. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2010-01-01

    Concerning International regulatory activities, we find for the european atomic energy community an entry into force of the lisbon treaty (2009), it amends the treaty on European union and replaces the treaty establishing the European Community by the new treaty on the functioning of the European Union; more, an amendment to council regulation on the conditions governing imports of agricultural products originating in third countries following the accident at the Chernobyl nuclear power station (2009). About International atomic energy agency is reported an open-ended meeting of technical and legal experts for sharing of information on states implementation of the code of conduct on the safety and security of radioactive sources and its supplementary guidance on the import and export of radioactive sources (2010). (N.C.)

  6. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2003-01-01

    Among international regulatory activities we find resolutions adopted by the IAEA general conference (2003), through European Union we find proposals for directives on nuclear safety and radioactive waste management, new regulation on the application of EURATOM safeguards, control of high activity sealed radioactive sources, recommendation on the protection and information of the public with regard to the continued contamination of certain wild food products following the Chernobyl accident, proposals for decisions authorizing the Member states to sign and ratify the Protocol to amend the Paris convention, p)proposals for a directive on environment liability with regard to the prevention and remedying of environmental damage, proposal of a regulation on the law applicable to non-contractual obligation. (N.C.)

  7. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2004-01-01

    The 48. session of the IAEA general conference was held in Vienna from 20 to 24 september 2004 with the participation of delegates from 125 members states and representatives of various international organisations. A number of resolutions were adopted by the conference in the following fields: nuclear safety, radiation, transport and waste safety. The general conference also adopted a resolution on measures to protect against nuclear terrorism. The Director General decided in 2003 to appoint a group of experts to explore and advise on issues related to nuclear liability. This group called the International Expert Group on Nuclear Liability (I.N.L.E.X.) consists of 20 experts members from nuclear power and non nuclear power countries and from shipping and non shipping states. It serves three major functions: to create a forum of expertise to explore and advise on issues related to nuclear liability; to enhance global adherence by nuclear and non nuclear states to an effective nuclear liability regime, inter alia, on the basis of the convention on supplementary compensation for nuclear damage and the annex thereto, the Vienna convention on civil liability for nuclear damage, the Paris convention on third party liability in the field of nuclear energy, the joint protocol relating to the application of the vienna convention and the paris convention and the amendments thereto; and to assist in the development and strengthening of the national nuclear liability legal frameworks in IAEA members states to protect the public and the environment and to enhance nuclear safety. The second part of international regulatory concerns a directive on public access to environmental information made by the European Parliament. (N.C.)

  8. International Drug Control Policy

    Science.gov (United States)

    2009-08-24

    Common illegal drugs include cannabis, cocaine, opiates, and synthetic drugs. International trade in these drugs represents a lucrative and what...into effect, decriminalizing “personal use” amounts of marijuana , heroin, cocaine, methamphetamine, and other internationally sanctioned drugs.15 While...President Calls for Legalizing Marijuana ,”CNN.com, May 13, 2009. 15 “Mexico Legalizes Drug Possession,” Associated Press, August 21, 2009. 16 In support

  9. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    1999-01-01

    The 43 rd Session of the IAEA General Conference was held in Vienna from 27 September to 1 October 1999 with delegations from 11 member states and representatives of various international organisations in attendance. Resolutions were adopted inter alia in the following areas: nuclear radiation and waste safety; strengthening IAEA technical co-operation; strengthening the IAEA's safeguards system; safeguards in the democratic people's republic of Korea; non proliferation safeguards in the middle east; illicit trafficking in nuclear materials and nuclear inspections in Iraq. The second part deals with the regulation laying down detailed rules for the application of the 1990 regulation on imports of agricultural products originating in third countries following the Chernobyl accident and recommendation on a classification system for solid radioactive waste. (A.L.B.)

  10. Challenges in orphan drug development and regulatory policy in China.

    Science.gov (United States)

    Cheng, Alice; Xie, Zhi

    2017-01-18

    While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research. Recently, the Chinese FDA set new regulatory guidelines for drugs being developed in China, including an expedited review process for life-saving treatments. In this review, we discuss the effects of these new policy changes on and suggest potential solutions to innovate orphan drug development in China.

  11. Canadian and international approaches to regulatory effectiveness

    International Nuclear Information System (INIS)

    Lojk, R.

    2014-01-01

    Regulatory effectiveness is an important attribute of any regulator, particularly nuclear regulators. As the nuclear industry has matured, and as the social landscape has changed, so have views on what constitutes regulatory effectiveness. Canada has evolved its regulatory structure and modernized its legislative framework and technical requirements and guidance over time. In addition, Canada continues to collaborate with international agencies, particularly the NEA and the IAEA, to ensure that there is a common understanding of the indicators and key attributes of regulatory effectiveness. This paper discusses Canadian and international views on the subject, including perspectives from other industries. (author)

  12. Regulatory and Economic Considerations of Retinal Drugs.

    Science.gov (United States)

    Shah, Ankoor R; Williams, George A

    2016-01-01

    The advent of anti-VEGF therapy for neovascular age-related macular degeneration and macular edema secondary to retinal vein occlusion and diabetes mellitus has prevented blindness in tens of thousands of people. However, the costs of these drugs are without precedent in ophthalmic drug therapeutics. An analysis of the financial implications of retinal drugs and the impact of the Food and Drug Administration on treatment of retinal disease must include not only an evaluation of the direct costs of the drugs and the costs associated with their administration, but also the cost savings which accrue from their clinical benefit. This chapter will discuss the financial and regulatory issues associated with retinal drugs. © 2016 S. Karger AG, Basel.

  13. Improving clinical drug development regulatory procedures for anticonvulsants

    Directory of Open Access Journals (Sweden)

    Janković Slobodan

    2015-01-01

    Full Text Available Background: Clinical development of antiepileptic drugs is demanding due to complex character of the disorder and to diversity of its forms and etiologies. Objective: The aim of this review was to suggest improvements in regulatory procedures for clinical development of antiepileptic drugs. Methods: The following databases of scientific articles were searched: MEDLINE, SCOPUS and SCINDEKS. In total 558 publications were retrieved. The types of articles selected were reviews, reports on clinical trials and letters to the Editor. Results: There are several changes of regulatory documents necessary for improving process of clinical development of antiepileptic drugs: preference of parallel groups design for add-on trials should be explicit; the noninferiority design for monotherapy clinical trials should be acceptable; restrictive formulations when trials of antiepileptic drugs in children are in question should be avoided; requirements in regard to the efficacy measures should be harmonized among the regulatory bodies; proactive attitude towards discovery of adverse events; and precise requirements for clinical trials specifically designed to prove anti-epileptogenic effects should be made clear. Conclusion: Current regulatory documents are incomplete in many aspects; an international effort to improve and harmonize guidelines for clinical development of antiepileptic drugs is necessary for improvement of this process.

  14. Recent Advances in Drug Development and Regulatory Science in China.

    Science.gov (United States)

    Chen, Jie; Zhao, Naiqing

    2018-01-01

    As the second largest pharmaceutical market with a great potential for future growth, China has drawn much attention from the global pharmaceutical community. With an increasing government investment in biomedical research, the domestic biopharmaceutical (biotechnological) companies in China are turning their attention to the development of innovative medicines and targeting the global market. To introduce innovative products to Chinese patients sooner, to improve the efficiency of its review and approval processes, and to harmonize its regulatory science with international standards, the China Food and Drug Administration (CFDA) has initiated a series of major changes to its policies and regulations. This paper presents a snapshot of China's pharmaceutical market, and research and development status, and introduces technical guidelines pertaining to clinical trials and new drug applications. The recent wave of ground-breaking reforms in CFDA's regulatory science is discussed. Examples of clinical trials and new drug applications are provided throughout the discussion.

  15. GENERIC DRUG IN GLOBAL MARKET AND REGULATORY ENVIRONMENT

    OpenAIRE

    Pankaj Kumar*, Bharti Mangla2, Satbir Singh, Arapna Rana

    2017-01-01

    Different regulatory authorities regulate the drug development in various countries of the world. Various Regulatory authority for generic drug application Food and Drug Administration (FDA), European Medicines Agency (EMA), Pharmaceutical and Medical Devices Agency (PMDA), Health Product and Food Branch (HPFB) Central Drug Standard of Organization (CDSO). Generic manufacturers may file an abbreviated New Drug Application (ANDA) that incorporates the safety/effectiveness data submitted by ori...

  16. International trade disputes in modern regulatory paradigm

    Directory of Open Access Journals (Sweden)

    Tamara Gordeeva

    2013-09-01

    Full Text Available This article studies the latest trends observed in the area of contradictory relations between countries with regard to international trade, which cause changes in the paradigm of international trade disputes. It has been found out that any state of inconsistent relations between the countries is recently characterized as a «trade war». It has been analyzed the notions of «dispute», «conflict», «war» according to international regulatory documents and determined the applicability of these terms depending on a number of criteria. It has been studied the evolution of the objects of international trade disputes since the time of ancient Greece until today, and new trends based on this have been revealed with regard to use of trade policy instruments that cause disputes between countries. Several specific examples of international trade disputes and causes of their occurrence have been considered. A quantitative analysis of international trade disputes in general and in relations between the leading countries in terms of a number of the trade disputes in which they were involved has been performed.

  17. International Consensus on drug allergy.

    Science.gov (United States)

    Demoly, P; Adkinson, N F; Brockow, K; Castells, M; Chiriac, A M; Greenberger, P A; Khan, D A; Lang, D M; Park, H-S; Pichler, W; Sanchez-Borges, M; Shiohara, T; Thong, B Y- H

    2014-04-01

    When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of

  18. Regulatory perspective on remaining challenges for utilization of pharmacogenomics-guided drug developments.

    Science.gov (United States)

    Otsubo, Yasuto; Ishiguro, Akihiro; Uyama, Yoshiaki

    2013-01-01

    Pharmacogenomics-guided drug development has been implemented in practice in the last decade, resulting in increased labeling of drugs with pharmacogenomic information. However, there are still many challenges remaining in utilizing this process. Here, we describe such remaining challenges from the regulatory perspective, specifically focusing on sample collection, biomarker qualification, ethnic factors, codevelopment of companion diagnostics and means to provide drugs for off-target patients. To improve the situation, it is important to strengthen international harmonization and collaboration among academia, industries and regulatory agencies, followed by the establishment of an international guideline on this topic. Communication with a regulatory agency from an early stage of drug development is also a key to success.

  19. A regulatory science viewpoint on botanical–drug interactions

    Directory of Open Access Journals (Sweden)

    Manuela Grimstein

    2018-04-01

    Full Text Available There is a continued predisposition of concurrent use of drugs and botanical products. Consumers often self-administer botanical products without informing their health care providers. The perceived safety of botanical products with lack of knowledge of the interaction potential poses a challenge for providers and both efficacy and safety concerns for patients. Botanical–drug combinations can produce untoward effects when botanical constituents modulate drug metabolizing enzymes and/or transporters impacting the systemic or tissue exposure of concomitant drugs. Examples of pertinent scientific literature evaluating the interaction potential of commonly used botanicals in the US are discussed. Current methodologies that can be applied to advance our efforts in predicting drug interaction liability is presented. This review also highlights the regulatory science viewpoint on botanical–drug interactions and labeling implications. Keywords: Drug interaction, Botanical product, St. John's wort, Fruit juices, Regulatory science

  20. The Dutch drug policy from a regulatory perspective

    NARCIS (Netherlands)

    Spapens, A.C.M.; Müller, T.; Van de Bunt, H.G.

    2015-01-01

    Starting in the 1970s, the Netherlands developed a regulatory regime for narcotic drugs by distinguishing between hashish and marihuana (“soft drugs”) and other drugs (“hard drugs”). The authorities decided to cease prosecuting the possession of consumer quantities of the former type and to allow

  1. Regulatory considerations concerning IND radiopharmaceutical drug products

    International Nuclear Information System (INIS)

    Nissel, M.

    1985-01-01

    The Food and Drug Administration is charged by the Food, Drug, and Cosmetic Act, as presently amended, to assure that any drug introduced into interstate commerce is safe and effective for the purposes for which it is labeled. A radiopharmaceutical is, by definition, a new drug unless there is in effect an approved New Drug Application (NDA) for it. Before the data for the NDA are compiled, investigative studies have to be done. Before such studies can be performed in humans, an exemption from the Act is necessary. This exemption, technically the Claimed Exemption for an Investigational New Drug, is termed the IND. Both the scientific and the administrative requirements for an IND are discussed. For radiopharmaceutical drug products (RDP's), the radiation hazards, as well as the pharmacological ones, must be documented. Should the early studies demonstrate a potential for efficacy in a certain condition or disease state, an investigative protocol for an extended clinical trial is presented. The necessary requirements for Institutional Review Board (IRB) approval and consent forms are discussed. For certain research purposes, uniquely for radioactive drugs, an IND is not required for certain specific studies; the requirements for such a research study, conducted under the auspices of an approved radioactive drug research committee, are outlined

  2. 77 FR 26413 - Promoting International Regulatory Cooperation

    Science.gov (United States)

    2012-05-04

    ... as such in the Unified Agenda of Federal Regulatory and Deregulatory Actions, on RegInfo.gov , and on... engage in various forms of collaboration and communication with respect to regulations, in particular a...

  3. Drug-device combination products: regulatory landscape and market growth.

    Science.gov (United States)

    Bayarri, L

    2015-08-01

    Combination products are therapeutic and diagnostic products that combine drugs, devices and/or biological products, leading to safer and more effective treatments thanks to careful and precise drug targeting, local administration and individualized therapy. These technologies can especially benefit patients suffering from serious diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes, among others. On the other hand, drug-device combination products have also introduced a new dynamic in medical product development, regulatory approval and corporate interaction. Due to the increasing integration of drugs and devices observed in the latest generation of combination products, regulatory agencies have developed specific competences and regulations over the last decade. Manufacturers are required to fully understand the specific requirements in each country in order to ensure timely and accurate market access of new combination products, and the development of combination products involves a very specific pattern of interactions between manufacturers and regulatory agencies. The increased sophistication of the products brought to market over the last couple of decades has accentuated the need to develop drugs and devices collaboratively using resources from both industries, fostering the need of business partnering and technology licensing. This review will provide a global overview of the market trends, as well as (in the last section) an analysis of the drug-device combination products approved by the FDA during the latest 5 years. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

  4. Drug lag and key regulatory barriers in the emerging markets

    Directory of Open Access Journals (Sweden)

    Harriet Wileman

    2010-01-01

    This work concludes that the overall relative drug lag in the emerging markets has decreased over time and that there are seven key regulatory barriers which need to be targeted in order to make further improvements; ′Western Approval′, local clinical development (LCD, Certificate of Pharmaceutical Product (CPP, Good Manufacturing Practice (GMP, pricing approval, document authentication and harmonisation.

  5. 77 FR 47078 - 2012 Parenteral Drug Association/Food and Drug Administration Joint Regulatory Conference...

    Science.gov (United States)

    2012-08-07

    ... foundations, emerging technologies and innovations in regulatory science, as well as the current quality and... of today's leading pharmaceutical companies present case studies on how they employ global strategies... Contract Manufacturing Organizations Contract Agreements Drug Safety Emerging Active Pharmaceutical...

  6. 78 FR 20325 - 2013 Parenteral Drug Association/Food and Drug Administration Joint Regulatory Conference...

    Science.gov (United States)

    2013-04-04

    ... foundations, emerging technologies and innovations in regulatory science, as well as the current quality and... strategies, while industry professionals from some of today's leading pharmaceutical companies present case.... Drug Safety. Emerging Active Pharmaceutical Ingredients (API) Regulations. Investigations. Emerging API...

  7. Guidelines for IAEA International Regulatory Review Teams (IRRTs)

    International Nuclear Information System (INIS)

    1993-04-01

    This document is intended to be used by International regulatory review teams in reviewing the activities of a regulatory body as applicable to the regulation of nuclear power plants. The mission will, however, take note of any other activities of the regulatory body when drawing up the review report. The document does not specifically deal with the functions of a regulatory body responsible for other types of nuclear facilities or related nuclear activities, but it is intended that the concepts presented in the document could be applied where appropriate. Refs

  8. A regulatory science viewpoint on botanical-drug interactions.

    Science.gov (United States)

    Grimstein, Manuela; Huang, Shiew-Mei

    2018-04-01

    There is a continued predisposition of concurrent use of drugs and botanical products. Consumers often self-administer botanical products without informing their health care providers. The perceived safety of botanical products with lack of knowledge of the interaction potential poses a challenge for providers and both efficacy and safety concerns for patients. Botanical-drug combinations can produce untoward effects when botanical constituents modulate drug metabolizing enzymes and/or transporters impacting the systemic or tissue exposure of concomitant drugs. Examples of pertinent scientific literature evaluating the interaction potential of commonly used botanicals in the US are discussed. Current methodologies that can be applied to advance our efforts in predicting drug interaction liability is presented. This review also highlights the regulatory science viewpoint on botanical-drug interactions and labeling implications. Copyright © 2018. Published by Elsevier B.V.

  9. 4th IEA International CCS Regulatory Network Meeting

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-01

    On 9 and 10 May 2012, the IEA International CCS Regulatory Network (Network), launched in Paris in May 2008 to provide a neutral forum for CCS regulators, policy makers and stakeholders to share updates and views on CCS regulatory developments, held its fourth meeting at the International Energy Agency (IEA) offices in Paris, France. The aim of the meeting was to: provide an update on government efforts to develop and implement carbon capture and storage (CCS) legal and regulatory frameworks; and consider ways in which governments are dealing with some of the more difficult or complex aspects of CCS regulation. This report summarises the proceedings of the meeting.

  10. Maritime drug interdiction in international law

    NARCIS (Netherlands)

    Kruit, P.J.J. van der

    2007-01-01

    The study focuses on the interdiction of trafficking in illicit drugs at sea as one part of the general problem of illicit drug trafficking. More specifically, the study focuses on the legal framework for the interdiction of illicit maritime drug trafficking under international law. Firstly, the

  11. Public Health and International Drug Policy

    Science.gov (United States)

    Csete, Joanne; Kamarulzaman, Adeeba; Kazatchkine, Michel; Altice, Frederick; Balicki, Marek; Buxton, Julia; Cepeda, Javier; Comfort, Megan; Goosby, Eric; Goulão, João; Hart, Carl; Horton, Richard; Kerr, Thomas; Lajous, Alejandro Madrazo; Lewis, Stephen; Martin, Natasha; Mejía, Daniel; Mathiesson, David; Obot, Isidore; Ogunrombi, Adeolu; Sherman, Susan; Stone, Jack; Vallath, Nandini; Vickerman, Peter; Zábranský, Tomáš; Beyrer, Chris

    2016-01-01

    access to social welfare programmes for people who use drugs would be useful indicators. All drug policies should also be monitored and evaluated as to their impact on racial and ethnic minorities, women, children and young people, and people living in poverty.Scientific approach to regulated markets: Move gradually toward regulated drug markets and apply the scientific method to their evaluation. While regulated legal drug markets are not politically possible in the short term in some places, the harms of criminal markets and other consequences of prohibition catalogued in this report are likely to lead more countries (and more US states) to move gradually in that direction, a direction we endorse. As those decisions are taken, we urge governments and researchers to apply the scientific method and ensure independent, multidisciplinary and rigorous evaluation of regulated markets to draw lessons and inform improvements in regulatory practices, and to continue evaluating and improving. We urge health professionals in all countries to inform themselves and join debates on drug policy at all levels. True to the stated goals of the international drug control regime, it is possible to have drug policy that contributes to the health and well-being of humankind, but not without bringing to bear the evidence of the health sciences and the voices of health professionals. PMID:27021149

  12. Problems in the regulatory policy of the drug market

    Science.gov (United States)

    Miziara, Nathália Molleis; Coutinho, Diogo Rosenthal

    2015-01-01

    OBJECTIVE Analyze the implementation of drug price regulation policy by the Drug Market Regulation Chamber. METHODS This is an interview-based study, which was undertaken in 2012, using semi-structured questionnaires with social actors from the pharmaceutical market, the pharmaceuticals industry, consumers and the regulatory agency. In addition, drug prices were compiled based on surveys conducted in the state of Sao Paulo, at the point of sale, between February 2009 and May 2012. RESULTS The mean drug prices charged at the point of sale (pharmacies) were well below the maximum price to the consumer, compared with many drugs sold in Brazil. Between 2009 and 2012, 44 of the 129 prices, corresponding to 99 drugs listed in the database of compiled prices, showed a variation of more than 20.0% in the mean prices at the point of sale and the maximum price to the consumer. In addition, many laboratories have refused to apply the price adequacy coefficient in their sales to government agencies. CONCLUSIONS The regulation implemented by the pharmaceutical market regulator was unable to significantly control prices of marketed drugs, without succeeding to push them to levels lower than those determined by the pharmaceutical industry and failing, therefore, in its objective to promote pharmaceutical support for the public. It is necessary reconstruct the regulatory law to allow market prices to be reduced by the regulator as well as institutional strengthen this government body. PMID:26083945

  13. Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

    Science.gov (United States)

    Hamilton, Gregory S

    2015-09-01

    Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  14. The stages of the international drug control system.

    Science.gov (United States)

    Carstairs, Catherine

    2005-01-01

    This paper argues that the history of the international drug control system of the League of Nations/United Nations can be divided into three cumulative stages. The first stage, the supply stage, dates back to early part of the 20th century, and aimed to reduce the supply of drugs through careful monitoring and trade regulations. This has remained the dominant control strategy. In the middle of the century, demand control, in the form of treatment and criminalization of the individual user, began to appear. This was the least successful stage. Finally, in the 1980s, the dangers of the drug traffic assumed an important place on the international agenda and measures to reduce drug-related organized crime were enacted. To date, this has been a process of proliferation of regulatory strategies. Recently, new challenges to the international drug control system have emerged, including well-funded non-governmental organizations critical of the war on drugs, and the adoption of harm reduction measures in national policies around the world.

  15. Regulatory aspects of oncology drug safety evaluation: Past practice, current issues, and the challenge of new drugs

    International Nuclear Information System (INIS)

    Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M. Stacey; McGuinn, W. David; Verbois, S. Leigh

    2010-01-01

    The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

  16. Improvement of Pediatric Drug Development: Regulatory and Practical Frameworks.

    Science.gov (United States)

    Tsukamoto, Katusra; Carroll, Kelly A; Onishi, Taku; Matsumaru, Naoki; Brasseur, Daniel; Nakamura, Hidefumi

    2016-03-01

    A dearth in pediatric drug development often leaves pediatricians with no alternative but to prescribe unlicensed or off-label drugs with a resultant increased risk of adverse events. We present the current status of pediatric drug development and, based on our data analysis, clarify the problems in this area. Further action is proposed to improve the drug development that has pediatric therapeutic orphan status. We analyzed all Phase II/III and Phase III trials in ClinicalTrials.gov that only included pediatric participants (Performance index, an indicator of pediatric drug development, was calculated by dividing the annual number of pediatric clinical trials by million pediatric populations acquired from Census.gov. Effects of the 2 Japanese premiums introduced in 2010, for the enhancement of pediatric drug development, were analyzed by comparing mean performance index prepremiums (2006-2009) and postpremiums (2010-2014) among Japan, the European Union, and the United States. The European Union Clinical Trials Register and published reports from the European Medicines Agency were also surveyed to investigate the Paediatric Committee effect on pediatric clinical trials in the European Union. Mean difference of the performance index in prepremiums and postpremiums between Japan and the European Union were 0.296 (P 15% after 2008. Recruitment and ethical obstacles make conducting pediatric clinical trials challenging. An improved operational framework for conducting clinical trials should mirror the ever-improving regulatory framework that incentivizes investment in pediatric clinical trials. Technological approaches, enhancements in electronic medical record systems, and community approaches that actively incorporate input from physicians, researchers, and patients could offer a sustainable solution to recruitment of pediatric study participants. The key therefore is to improve pediatric pharmacotherapy collaboration among industry, government, academia, and

  17. Determinants of Effective Information Transfer in International Regulatory Standards Adoption

    Science.gov (United States)

    Popescu, Denisa

    2010-01-01

    The role of international regulatory standards within the current global environment has become of the most importance. The age of the global system and free market capitalism carried us into the unprecedented age of regulations, and standard setting. Regulations are now becoming the emerging mode of global governance. This study focuses on…

  18. Stability Testing of Herbal Drugs: Challenges, Regulatory Compliance and Perspectives.

    Science.gov (United States)

    Bansal, Gulshan; Suthar, Nancy; Kaur, Jasmeen; Jain, Astha

    2016-07-01

    Stability testing is an important component of herbal drugs and products (HDPs) development process. Drugs regulatory agencies across the globe have recommended guidelines for the conduct of stability studies on HDPs, which require that stability data should be included in the product registration dossier. From the scientific viewpoint, numerous chemical constituents in an herbal drug are liable to varied chemical reactions under the influence of different conditions during its shelf life. These reactions can lead to altered chemical composition of HDP and consequently altered therapeutic profile. Many reports on stability testing of HDPs have appeared in literature since the last 10 years. A review of these reports reveals that there is wide variability in temperature (-80 to 100 °C), humidity (0-100%) and duration (a few hours-36 months) for stability assessment of HDPs. Of these, only 1% studies are conducted in compliance with the regulatory guidelines for stability testing. The present review is aimed at compiling all stability testing reports, understanding key challenges in stability testing of HDPs and suggesting possible solutions for these. The key challenges are classified as chemical complexity and biochemical composition variability in raw material, selection of marker(s) and influences of enzymes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Drug shortages in Israel: regulatory perspectives, challenges and solutions.

    Science.gov (United States)

    Schwartzberg, Eyal; Ainbinder, Denize; Vishkauzan, Alla; Gamzu, Ronni

    2017-01-01

    and temporary drug shortages are being implemented in Israel, such as suspending any further reductions in drug prices below 17 new Israeli shekels, instructing all MAHs to maintain no less than 1 month supply of all registered and non-registered drugs in Israel and allowing an expedited registration pathway for well-established use/grandfather drugs. Drug shortages pose significant public health hazards worldwide. Early notification to the MoH and open dialog with MAHs are essential for managing DSs and mitigating their impact. Despite the efforts carried out by health regulatory authorities worldwide, DSs still pose a significant threat to public health.

  20. Evolving regulatory paradigm for proarrhythmic risk assessment for new drugs.

    Science.gov (United States)

    Vicente, Jose; Stockbridge, Norman; Strauss, David G

    Fourteen drugs were removed from the market worldwide because their potential to cause torsade de pointes (torsade), a potentially fatal ventricular arrhythmia. The observation that most drugs that cause torsade block the potassium channel encoded by the human ether-à-go-go related gene (hERG) and prolong the heart rate corrected QT interval (QTc) on the ECG, led to a focus on screening new drugs for their potential to block the hERG potassium channel and prolong QTc. This has been a successful strategy keeping torsadogenic drugs off the market, but has resulted in drugs being dropped from development, sometimes inappropriately. This is because not all drugs that block the hERG potassium channel and prolong QTc cause torsade, sometimes because they block other channels. The regulatory paradigm is evolving to improve proarrhythmic risk prediction. ECG studies can now use exposure-response modeling for assessing the effect of a drug on the QTc in small sample size first-in-human studies. Furthermore, the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a new in vitro paradigm for cardiac safety evaluation of new drugs that provides a more accurate and comprehensive mechanistic-based assessment of proarrhythmic potential. Under CiPA, the prediction of proarrhythmic potential will come from in vitro ion channel assessments coupled with an in silico model of the human ventricular myocyte. The preclinical assessment will be checked with an assessment of human phase 1 ECG data to determine if there are unexpected ion channel effects in humans compared to preclinical ion channel data. While there is ongoing validation work, the heart rate corrected J-T peak interval is likely to be assessed under CiPA to detect inward current block in presence of hERG potassium channel block. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Development of an international BRC [Below Regulatory Concern] limit

    International Nuclear Information System (INIS)

    Kennedy, W.E. Jr.

    1987-07-01

    The International Atomic Energy Agency (IAEA) has recently investigated the exemption from regulatory control of radiation sources containing limited quantities of radioactive materials. Early efforts were entitled de minimis and were aimed at establishing a philosophical basis and radiation dose limits. The main objectives of more recent work on exemption are to illustrate a method for developing practical radiological criteria, to establish generic criteria, and to determine the practicability of the preliminary exemption principles. The method used to develop the criteria relies on models to evaluate the potential radiation exposure pathways and scenarios for individuals and population groups potentially present following the unrestricted release of materials. This paper describes the assessment methods, presents the generic results expressed in terms of the limiting concentrations of selected radionuclides in municipal waste, and provides a comparison with recent regulatory efforts in the United States for considering selected wastes being Below Regulatory Concern (BRC). 17 refs., 4 tabs

  2. Strengthening the regulatory control of consumer goods through international harmonization

    International Nuclear Information System (INIS)

    Yus Rusdian Akhmad

    2013-01-01

    The International Atomic Energy Agency (IAEA) is currently working on a recommendation in the form of guidelines for regulating consumer goods. Preparation of this document has a significant dimension of international issues, especially in terms of the application of the principles of justification and application of the concept of exemption. International harmonization among regulators ranging from the regional to the global level is a central issue and considering the complex issues that arise in addition to covering the scientific aspects also involve consideration of the legal aspects or values espoused by any State which may differ from one another. PERKA BAPETEN on consumer goods is still in the preparation stage so that the discussion of the material will be useful for improving the quality of the regulation in time. There is a significant gap of understanding to the related materials by the parties concerned (between local and international parties were among the local party). This paper intends to propose the understanding and views on radiation protection and regulatory control for consumer goods and hopely could contributed significantly to strengthening its regulatory control which is primarily through a reduction in the gap of understanding to the related concept that potentially multi perceptions and encourage stronger cooperation among regulatory bodies. (author)

  3. Willingness to pay for adverse drug event regulatory actions.

    Science.gov (United States)

    Bouvy, Jacoline; Weemers, Just; Schellekens, Huub; Koopmanschap, Marc

    2011-11-01

    Regulatory requirements for the pharmaceutical industry have become increasingly demanding with respect to the safety and effectiveness of drugs. The objective of this study was to determine the willingness to pay (WTP), of both the Dutch general public and dialysis patients, for regulatory requirements related to reducing the risk of pure red cell aplasia (PRCA) associated with epoetin alpha use. A survey was carried out in April 2009. The Dutch general public (n = 422) was approached through a survey sampling agency. Patients (n = 112) were included through several Dutch dialysis clinics because they are often treated with epoetin alpha and therefore were expected to have a higher WTP than the general public. The survey aimed to determine the WTP for reducing the risk of PRCA in epoetin alpha users from 4.5 to 0 per 10 000 patients per year, based on regulatory actions that have been taken by the European Medicines Agency (EMA). WTP was determined via a payment scale and an open-ended follow-up question. Patients were asked how much extra per year they would be willing to pay for their basic healthcare insurance. We used two censored regression models to test the association between WTP and a set of independent variables: a Tobit model with the stated WTP as the dependent variable and an interval regression model with the interval between the lower and upper bounds of the payment scale as the dependent variable. The patients' mean WTP was significantly higher (€46.52) than that of the general public (€24.40). The Tobit model showed significant associations (α = 0.05) with WTP for dialysis patients, risk perception and respondents' opinions on costs of healthcare. The interval regression model showed significant associations with WTP for the same variables as the Tobit model and for one additional variable (risk aversion). Income did not significantly affect WTP. A scenario with a 10-fold larger risk reduction did not increase WTP significantly

  4. The state of internal audit’s regulatory mandate

    Directory of Open Access Journals (Sweden)

    Christo Ackermann

    2016-08-01

    Full Text Available The importance of an effective internal audit function in South African municipalities have been recognised insofar as internal audit functions are legally mandated to exist within municipalities. This also means that legally, internal audit has certain mandates which must be fulfilled in order to add value to management and audit committees, and ultimately, to the board of directors. Even though internal audit is sanctioned by this important legal mandate, evidence shows that internal audit does not always fulfil this mandate. This state of affairs has prompted a detailed review of the relevant laws and regulations governing the work of internal audit in South African municipalities in order to determine the extent to which key stakeholders find the regulatory work of internal audit useful in discharging their (stakeholders’ oversight responsibilities. Questionnaires were administered to audit committees. The results summarise the extent to which internal audit’s work assists audit committees in their oversight responsibilities as this ultimately affects the ability of audit committees to fulfil these responsibilities to the board of directors. The results indicate that audit committees are greatly dependent on internal audit as a provider of assurance on a variety of legally mandated variables. The results of this study can be used as a measure of best practice of the legally mandated duties performed by internal audit. It can also be used by other researchers in comparative studies and by practitioners to benchmark their work in order to better serve audit committees and ultimately, the board of directors

  5. Case law. Administrative decisions. National legislative and regulatory activities. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2007-01-01

    The different subjects are as follow: judgment on Konrad repository project (Germany), Measures for the dismantling of Barsebaeck (Sweden), amendment to the criminal code (Argentina), Australian nuclear science and technology organisation amendment act, commonwealth radioactive waste management legislation amendment (Australia), amendments to the radiation act and radiation decree (Finland), decree on securing financing for nuclear charges, decree licensing the construction of the basic nuclear installation Flamanville 3 comprising an EPR reactor (France), amendment to the act on preventive radiation protection, administrative provisions on the supervision of environmental radioactivity, ordinance on radioactive drugs, amendment to the ordinance on the treatment of foodstuffs with radiation, European agreement relating to the international transportation of dangerous goods by road, ordinance on the transportation of dangerous goods by road and rail, ordinance to amend the R.I.D. regulations, ordinance on the transportation of dangerous goods on the Rhine and Mosel rivers, amendments to the 1961 foreign trade act and to the 1993 foreign trade ordinance (Germany), regulations in the field of radiation protection (Iceland), decree on nuclear reactor licensing (Indonesia), carriage of dangerous goods by road act (Ireland), decree on emergency planning with regard to the transport of radioactive and fissile materials (Italy), covenant between the government and the Borssele operator concerning the life extension (Netherlands), consolidated edition of the 1965 radiation protection act (New Zealand), regulation on ionizing radiation sources (Poland), decision approving the structure and organisation of the romanian nuclear agency, amendment of the 2003 decision approving the internal rules of the national commission for the control of nuclear activities, amendment of the 2003 ordinance on the management of spent nuclear fuel and radioactive waste including final disposal

  6. Guidelines for IAEA International Regulatory Review Teams (IRRTs)

    International Nuclear Information System (INIS)

    2002-01-01

    The IAEA International Regulatory Review Team (IRRT) programme provides advice and assistance to Member States to strengthen and enhance the effectiveness of the nuclear regulatory body whilst recognizing the ultimate responsibility of each Member State for nuclear safety. The IRRT programme, initiated in 1989, is not restricted to any particular group of Member States, whether developing or industrialized, but is available to all countries with nuclear installations in operation or approaching operation. The basic concepts, purposes and functions of a national regulatory body are well recognized in all Member States having a nuclear power programme. The IAEA Safety Standards Series publication entitled 'Legal and Governmental Infrastructure for Nuclear, Radiation, Radioactive Waste and Transport Safety, Safety: Requirements', No. GS-R-1 (2000), provides a general consensus reference for the practices necessary for a national organization to fulfil the regulatory purposes and discharge the regulatory functions. The Requirements also defines the terms used in these guidelines. The guidance given in the Requirements recognizes that the organizational structure and regulatory processes will vary from country to country depending on their existing constitutional, legal and administrative systems; the size and structure of their nuclear programme; the technical skills and professional and financial resources available to their regulatory body, and social customs and cultural traditions. The objective of this report is to provide guidance on the basic structure of an IRRT mission and provide a common reference both across the various areas covered by an IRRT mission and across all the missions in the programme. As such, it is addressed, principally, to the team members of IRRT missions but it also provides guidance to a host regulatory body receiving a mission. This report identifies the objectives of the IRRT mission and sets out the scope of the topic areas that are

  7. United Nations International Drug Control Programme responds

    Directory of Open Access Journals (Sweden)

    Michael Platzer

    2002-01-01

    Full Text Available [First paragraph] We would like to reply to the article written by Axel Klein entitled, "Between the Death Penalty and Decriminalization: New Directions for Drug Control in the Commonwealth Caribbean" published in NWIG 75 (3&4 2001. We have noted a number of factual inaccuracies as well as hostile comments which portray the United Nations International Drug Control Programme in a negative light. This reply is not intended to be a critique of the article, which we find unbalanced and polemical, but rather an alert to the tendentious statements about UNDCP, which we feel should be corrected.

  8. The Regulatory Cooperation Forum, an Opportunity to Strengthen International Cooperation

    International Nuclear Information System (INIS)

    Lachaume, J.L.; Mamoru, M.

    2016-01-01

    The Regulatory Cooperation Forum (RCF) is a member-driven forum of nuclear power regulators created in 2010 that promotes the sharing of regulatory knowledge and experience through international cooperation and collaboration using the IAEA Safety Standards as its basis. The RCF involves countries with advanced nuclear power programmes, countries embarking on nuclear power for the first time and countries with smaller programmes considering expansion. The primary objectives of the RCF are: • To promote collaboration and cooperation among RCF members to improve coordination of support for regulatory infrastructure development; • To contribute to achieving and sustaining a high level of nuclear safety, consistent with the IAEA Safety Standards and Guidance; • To optimize resources among RCF members and avoid unnecessary support duplication through improved coordination. Membership of the RCF is open to all Member States of the IAEA. Participants in RCF activities will normally be senior representatives from regulatory bodies in Member States and from other providers, including the IAEA, European Commission (EC) and the Nuclear Energy Agency (NEA) of the Organization for Economic Co-operation and Development (OECD). So far, more than 30 countries are members of the RCF. The RCF has developed Action Plans to support Jordan, Vietnam, Belarus and Poland. The IAEA’s Nuclear Safety Action Plan urges Member States to strengthen the effectiveness of national regulatory bodies as well as base the development of their nuclear infrastructures on IAEA Safety Standards. The RCF assists Member States in implementing both of these actions for embarking, existing and expanding nuclear programmes. (author)

  9. International trends in regulatory principles, criteria and compliance

    International Nuclear Information System (INIS)

    Bragg, K.A.

    1996-01-01

    This paper is intended to summarize recent international developments on regulatory principles, criteria and related compliance issues. It focuses on the work within the IAEA undertaken by the Working Group on Principles and Criteria for Radioactive Waste Disposal and Within the NEA by another Working Group on the Regulatory Aspects of Future Human Actions at Radioactive Waste Disposal Sites. Both groups have been chaired by the author. The IAEA working group members are drawn from regulatory bodies and implementing organizations. Thus a balance is maintained between various points of view on topics such as the theory of radiation protection and its practical application. The group has a very flexible mandate and in practice the topics it chooses to address, and the priorities which are assigned to them, are selected by the group itself, under the direction of the new Waste Safety Standard Advisory Committee (WASSAC). The IAEA group is concerned with examining areas of importance to safety principles for waste disposal on which no consensus yet exists and with exploring new ideas and concepts. Because of the inherent uncertainty in such a process, no targets or schedules have been set for the group to produce reports, although it is recognised that if consensus is reached on an important issue then it should be documented. In contrast, the Radioactive Waste Safety Standards (RADWASS) programme of the IAEA has the aim of documenting the existing areas of consensus in a structured way and of doing so against preestablished timescales. The group meets annually and has had 5 meetings to date. The following sections summarize the main accomplishments of the group and indicate the status of some work that is well developed but has not yet been published. (author)

  10. Regulatory Assessment Technologies for Aging of Reactor Vessel Internals

    Energy Technology Data Exchange (ETDEWEB)

    Jhung, Myung Jo; Park, Jeong Soon; Ko, Hanok [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2013-10-15

    In order to develop the audit calculation system, it is required to develop crack evaluation, seismic analysis and thermal-hydraulic analysis techniques for RVIs so that integrity of RVIs under the aging environment can be evaluated and be assured. In addition, regulatory requirements including safety review and inspection guides should be developed in order to assure the quality and uniformity of safety reviews and inspections regarding aging assessment and management of RVIs. Since Reactor Vessel Internals (RVIs) are installed within the reactor pressure vessel and surround the fuel assemblies, some of them are exposed to the environment such as high neutron irradiation, high temperature and reactor coolant flow. Those environmental factors can cause damage to RVIs including cracks, loss of material, fatigue, loss of fracture toughness and change of dimension as the operation time of nuclear power plants (NPPs) increases. For long-term operation more than 40 years, aging management of RVIs is important. The final objectives of this study are to establish the audit calculation system for RVIs and to develop regulatory requirements for aging assessment and management of RVIs considering their operating conditions, materials, and possible aging mechanisms.

  11. Internal communication within the Slovak Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    Seliga, Mojmir

    2000-01-01

    One of the primary objectives of the Slovak Nuclear Regulatory Authority (UJD) Public Relations Program is to make available to the public full and complete information on UJD activities to assist the public in making informed judgments regarding UJD activities. The primary means of keeping the public informed about the regulatory activities and programs of the UJD is through the news media. A central state administration body, the UJD provides on request within its province in particular information on operational safety of nuclear energy installations independently of those responsible for the nuclear programme, thereby allowing the public and the media to control data and information on nuclear installations. A major element of providing information is the demonstration that the area of nuclear energy uses has its binding rules in the Slovak Republic and the observance thereof is controlled by the state through an independent institution - UJD. As early as 1995 were laid on the UJD the foundations of the concept of broadly keeping the public informed on UJD activity and the safety of nuclear installations by opening the UJD Information Centre. Information Centre provides by its activity communications with the public and mass media, which is instrumental in creating in the public a favourable picture of the independent state nuclear regulation. Internal and external communications are equally important

  12. 47 CFR 63.10 - Regulatory classification of U.S. international carriers.

    Science.gov (United States)

    2010-10-01

    ... demonstrates that the foreign affiliate lacks 50 percent market share in the international transport and the... 47 Telecommunication 3 2010-10-01 2010-10-01 false Regulatory classification of U.S. international... and Supplements § 63.10 Regulatory classification of U.S. international carriers. (a) Unless otherwise...

  13. The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

    Science.gov (United States)

    van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

    2015-07-15

    Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Accelerating resistance, inadequate antibacterial drug pipelines and international responses.

    Science.gov (United States)

    Theuretzbacher, Ursula

    2012-04-01

    The pandemic of multidrug-resistant (MDR) pathogens and their continuing spread is beyond dispute. In contrast to the past, today's antibacterial research and development (R&D) pipelines are nearly dry, failing to provide the flow of novel antibiotics required to match the clinical challenges of the multidrug resistance (MDR) crisis. Concerned over the rapidly worsening potential global healthcare crisis caused by MDR bacteria and the lack of robust drug pipelines, several multinational campaigns have issued policy recommendations and have initiated broad discussion with a goal of stimulating the development of novel antibacterial drugs and technologies. These activities have resulted in intensified co-operation between the USA and the EU. The recently announced extensive 'Action plan against the rising threats from antimicrobial resistance' substantially ramps up action within the EU. In recognising the potential crisis caused by MDR and the limited treatment options, the European Commission decided on an unprecedented approach to drive the search for novel antibiotics by integrating the pharmaceutical industry, the research capacities of universities and small companies supported by public funding along with pricing/reimbursement and regulatory bodies. The European Commission has shown leadership and put action plans in place. Only the future will tell whether these initiatives will help curb the impact of the MDR pandemic. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  15. Different contributions of internal reviewers and external experts to labelling decisions on therapeutic indications in new drug reviews in Japan.

    Science.gov (United States)

    Yokota, M; Kusama, M; Matsuki, N; Ono, S

    2013-12-01

    External experts play an important role in shaping regulatory decisions in the new drug review process in the United States, Europe and Japan. No rigorous study has been performed addressing how and to what extent external experts, in contrast to internal reviewers in the agency, influence the regulatory decisions during new drug reviews. We examined their contributions in Japanese regulatory reviews in contrast to the internal reviewers, focusing on the labelling decision on therapeutic indications. With the data set of 219 new molecular entities (NMEs) approved in Japan from 2000 to 2009, we observed how proposed indications in labelling were modified in a stepwise manner during the review process and conducted multinomial logistic analysis to examine the possible mechanism behind. We found that interim assessment of indications by the internal reviewers was modified substantially by the influence of the external experts in about 20% of the 219 NMEs. Our analysis suggested that internal reviewers provided their opinion mainly based on strict review discipline, whereas external experts added flexibility and reality to their reviews. Our analysis revealed different evaluations between internal reviewers and external experts during regulatory discussions in new drug reviews and how the external panel contributes to changing internal decisions. This study provides a new and quantitative approach to better label setting by emphasizing the contributions of each stakeholder in new drug reviews, which would improve the efficiency, quality and transparency of new drug reviews to enhance public health. © 2013 John Wiley & Sons Ltd.

  16. Regional and International Networking to Support the Energy Regulatory Commission of Thailand

    Energy Technology Data Exchange (ETDEWEB)

    Lavansiri, Direk; Bull, Trevor

    2010-09-15

    The Energy Regulatory Commission of Thailand is a new regulatory agency. The structure of the energy sector; the tradition of administration; and, the lack of access to experienced personnel in Thailand all pose particular challenges. The Commission is meeting these challenges through regional and international networking to assist in developing policies and procedures that allow it to meet international benchmarks.

  17. Unique characteristics of regulatory approval and pivotal studies of orphan anticancer drugs in Japan.

    Science.gov (United States)

    Nakayama, Hiroki; Tsukamoto, Katsura

    2018-04-17

    The approval of orphan anticancer drugs has increased, with the number exceeding that of non-orphan drugs in Japan in recent years. Although orphan anticancer drugs may have unique characteristics due to their rarity, these have not been fully characterized. We investigated anticancer drugs approved in Japan between April 2004 and November 2017 to reveal the characteristics of regulatory approval and pivotal studies on orphan anticancer drugs compared to non-orphan drugs. The median regulatory review time and number of patients in pivotal studies on orphan anticancer drugs (281.0 days [interquartile range, 263.3-336.0]; 222.5 patients [66.0-454.3]) were significantly lower than those on non-orphan drugs (353.0 days [277.0-535.5]; 521.0 patients [303.5-814.5], respectively) (P < 0.001). Phase II, non-randomized and non-controlled designs were more frequently used in pivotal studies on orphan anticancer drugs (45.9%, 41.9% and 43.2%) than non-orphan drugs (17.2%, 14.1% and 14.1%, respectively). Response rate was more commonly used as a primary endpoint in pivotal studies on orphan anticancer drugs (48.6%) than non-orphan drugs (17.2%). Indications limited by molecular features, second or later treatment line, and accelerated approval in the United States were associated with the use of response rate in orphan anticancer drug studies. In conclusion, we demonstrated that orphan anticancer drugs in Japan have unique characteristics compared to non-orphan drugs: shorter regulatory review and pivotal studies frequently using phase II, non-randomized, or non-controlled designs and response rate as a primary endpoint, with fewer patients.

  18. The evaluation of drug regulation - economic approaches into the valuation and evaluation of the drug regulatory framework

    NARCIS (Netherlands)

    Bouvy, J.C.

    2013-01-01

    The European pharmaceutical market is strictly regulated. Sufficient levels of quality, safety, and efficacy will have to be demonstrated before a pharmaceutical is allowed to enter the market. There is little evidence, however, that the current drug regulatory framework is achieving its goals of

  19. Mexico's "ley de narcomenudeo" drug policy reform and the international drug control regime.

    Science.gov (United States)

    Mackey, Tim K; Werb, Daniel; Beletsky, Leo; Rangel, Gudelia; Arredondo, Jaime; Strathdee, Steffanie A

    2014-11-14

    It has been over half a century since the landmark Single Convention on Narcotic Drugs was adopted, for the first time unifying international drug policy under a single treaty aimed at limiting use, manufacture, trade, possession, and trafficking of opiates, cannabis, and other narcotics. Since then, other international drug policy measures have been adopted, largely emphasizing enforcement-based approaches to reducing drug supply and use. Recently, in response to concerns that the historic focus on criminalization and enforcement has had limited effectiveness, international drug policies have begun to undergo a paradigm shift as countries seek to enact their own reforms to partially depenalize or deregulate personal drug use and possession. This includes Mexico, which in 2009 enacted national drug policy reform partially decriminalizing possession of small quantities of narcotics for personal consumption while also requiring drug treatment for repeat offenders. As countries move forward with their own reform models, critical assessment of their legal compatibility and effectiveness is necessary. In this commentary we conduct a critical assessment of the compatibility of Mexico's reform policy to the international drug policy regime and describe its role in the current evolving drug policy environment. We argue that Mexico's reform is consistent with flexibilities allowed under international drug treaty instruments and related commentaries. We also advocate that drug policy reforms and future governance efforts should be based on empirical evidence, emphasize harm reduction practices, and integrate evidence-based evaluation and implementation of drug reform measures.

  20. Regulatory research for waste disposal - Objectives and international approaches

    International Nuclear Information System (INIS)

    Wanner, Hans; Fischer-Appelt, Klaus; Pescatore, Claudio

    2011-01-01

    The question of active involvement of nuclear regulatory and supervisory bodies in research and development (R and D) projects has become a topic of increasing interest in recent years. The way in which research is included in regulatory activities varies from country to country, ranging from countries with no regulatory R and D activities to countries with extensive activities which are often carried out by independent research organisations acting on behalf of the regulatory body. The present report outlines (part 1) the potential merits of R and D work carried out by the regulator, and summarizes (part 2) the results of a questionnaire that was circulated among the members of the Regulators' Forum of NEA's Radioactive Waste Management Committee in 2009. Part 3 presents the conclusions of discussions within the RWMC-RF. The detailed answers to the questionnaire are also provided

  1. Regulatory issues with multiplicity in drug approval: Principles and controversies in a changing landscape.

    Science.gov (United States)

    Benda, Norbert; Brandt, Andreas

    2018-01-01

    Recently, new draft guidelines on multiplicity issues in clinical trials have been issued by European Medicine Agency (EMA) and Food and Drug Administration (FDA), respectively. Multiplicity is an issue in clinical trials, if the probability of a false-positive decision is increased by insufficiently accounting for testing multiple hypotheses. We outline the regulatory principles related to multiplicity issues in confirmatory clinical trials intended to support a marketing authorization application in the EU, describe the reasons for an increasing complexity regarding multiple hypotheses testing and discuss the specific multiplicity issues emerging within the regulatory context and being relevant for drug approval.

  2. Giving Drugs a Second Chance: Overcoming Regulatory and Financial Hurdles in Repurposing Approved Drugs As Cancer Therapeutics.

    Science.gov (United States)

    Hernandez, J Javier; Pryszlak, Michael; Smith, Lindsay; Yanchus, Connor; Kurji, Naheed; Shahani, Vijay M; Molinski, Steven V

    2017-01-01

    The repositioning or "repurposing" of existing therapies for alternative disease indications is an attractive approach that can save significant investments of time and money during drug development. For cancer indications, the primary goal of repurposed therapies is on efficacy, with less restriction on safety due to the immediate need to treat this patient population. This report provides a high-level overview of how drug developers pursuing repurposed assets have previously navigated funding efforts, regulatory affairs, and intellectual property laws to commercialize these "new" medicines in oncology. This article provides insight into funding programs (e.g., government grants and philanthropic organizations) that academic and corporate initiatives can leverage to repurpose drugs for cancer. In addition, we highlight previous examples where secondary uses of existing, Food and Drug Administration- or European Medicines Agency-approved therapies have been predicted in silico and successfully validated in vitro and/or in vivo (i.e., animal models and human clinical trials) for certain oncology indications. Finally, we describe the strategies that the pharmaceutical industry has previously employed to navigate regulatory considerations and successfully commercialize their drug products. These factors must be carefully considered when repurposing existing drugs for cancer to best benefit patients and drug developers alike.

  3. Giving Drugs a Second Chance: Overcoming Regulatory and Financial Hurdles in Repurposing Approved Drugs As Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    J. Javier Hernandez

    2017-11-01

    Full Text Available The repositioning or “repurposing” of existing therapies for alternative disease indications is an attractive approach that can save significant investments of time and money during drug development. For cancer indications, the primary goal of repurposed therapies is on efficacy, with less restriction on safety due to the immediate need to treat this patient population. This report provides a high-level overview of how drug developers pursuing repurposed assets have previously navigated funding efforts, regulatory affairs, and intellectual property laws to commercialize these “new” medicines in oncology. This article provides insight into funding programs (e.g., government grants and philanthropic organizations that academic and corporate initiatives can leverage to repurpose drugs for cancer. In addition, we highlight previous examples where secondary uses of existing, Food and Drug Administration- or European Medicines Agency-approved therapies have been predicted in silico and successfully validated in vitro and/or in vivo (i.e., animal models and human clinical trials for certain oncology indications. Finally, we describe the strategies that the pharmaceutical industry has previously employed to navigate regulatory considerations and successfully commercialize their drug products. These factors must be carefully considered when repurposing existing drugs for cancer to best benefit patients and drug developers alike.

  4. Equivalence of complex drug products: advances in and challenges for current regulatory frameworks.

    Science.gov (United States)

    Hussaarts, Leonie; Mühlebach, Stefan; Shah, Vinod P; McNeil, Scott; Borchard, Gerrit; Flühmann, Beat; Weinstein, Vera; Neervannan, Sesha; Griffiths, Elwyn; Jiang, Wenlei; Wolff-Holz, Elena; Crommelin, Daan J A; de Vlieger, Jon S B

    2017-11-01

    Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

  5. Influence of drug molecules on regulatory B cells.

    Science.gov (United States)

    Amrouche, Kahina; Jamin, Christophe

    2017-11-01

    By their suppressive functions, regulatory B (Breg) cells are considered as key elements in the control and development of various disease states. Many signals can induce Bregs in vivo and in vitro and often from heterogeneous populations. Several specific signals delivered in a timely immunological context contribute to the establishment of Bregs. These are endogenous and physiological signals or stimuli, widely discussed in the literature participating in the establishment of an effective immune response. However, exogenous signals, much less clearly identified can also be considered as Bregs inducers. These extrinsic signals are capable of directly or indirectly influencing the suppressive capacity of Bregs, but also their expansion and functional restoration in its absence. Faced with the excitement generated by the development of processes favoring the expansion of Bregs in mice for therapeutic purposes, the challenge today is to extrapolate such approaches in humans. This perspective may already be in effect. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Implementation of in vitro replacement technologies in regulatory drug testing - An innovation systems perspective

    NARCIS (Netherlands)

    Kooijman, M.; Van Meer, P.J.K.; Moors, E.H.M.; Hekkert, M.P.; Schellekens, H.

    2011-01-01

    The replacement of in vivo methods by in vitro methods in regulatory drug testing is rare. The aim of this research is to identify barriers and drivers of the replacement of in vivo methods by in vitro methods in Europe. We studied two cases. The first case is the Draize eye test. Since 2009, the in

  7. A regulatory perspective on the abuse potential evaluation of novel stimulant drugs in the United States.

    Science.gov (United States)

    Calderon, Silvia N; Klein, Michael

    2014-12-01

    In the United States of America (USA), the abuse potential assessment of a drug is performed as part of the safety evaluation of a drug under development, and to evaluate if the drug needs to be subject to controls that would minimize the abuse of the drug once on the market. The assessment of the abuse potential of new drugs consists of a scientific and medical evaluation of all data related to abuse of the drug. This paper describes the regulatory framework for evaluating the abuse potential of new drugs, in general, including novel stimulants. The role of the United States Food and Drug Administration (FDA) in the evaluation of the abuse potential of drugs, and its role in drug control are also discussed. A definition of abuse potential, an overview of the currently accepted approaches to evaluating the abuse potential of a drug, as well as a description of the criteria that applies when recommending a specific level of control (i.e., a Schedule) for a drug under the Controlled Substances Act (CSA). This article is part of the Special Issue entitled 'CNS Stimulants'. Published by Elsevier Ltd.

  8. International regulatory control of the transport of radioactive materials

    International Nuclear Information System (INIS)

    Swindell, G.E.

    1979-01-01

    The development of the IAEA regulations on the transport of radioactive materials and the background for the adoption of these regulations by the various international organizations responsible for regulating the different modes of international transport of hazardous materials is briefly discussed

  9. 75 FR 66410 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2010-10-28

    ...-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to the Sales Value Fee October 22, 2010. Pursuant to Section 19(b... hereby given that, on October 14, 2010, the International Securities Exchange, LLC (the ``Exchange'' or...

  10. 75 FR 62900 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2010-10-13

    ...-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to a Market Maker Incentive Plan for Foreign Currency Options... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on October 4, 2010, International Securities...

  11. 76 FR 1488 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2011-01-10

    ...-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to a Market Maker Incentive Plan for Foreign Currency Options... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 28, 2010, the International...

  12. 75 FR 2913 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2010-01-19

    ...-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to a Market Maker Incentive Plan for Foreign Currency Options...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 31, 2009, the International...

  13. Maternal Depression, Locus of Control, and Emotion Regulatory Strategy as Predictors of Preschoolers' Internalizing Problems

    Science.gov (United States)

    Coyne, Lisa W.; Thompson, Alysha D.

    2011-01-01

    Childhood internalizing problems may occur as early as preschool, tend to be stable over time, and undermine social and academic functioning. Parent emotion regulatory behaviors may contribute to child internalizing problems and may be especially important during the preschool years when parents model emotion coping and regulation for their…

  14. 75 FR 2915 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed...

    Science.gov (United States)

    2010-01-19

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61317; File No. SR-ISE-2009-103] Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed Rule Change Relating to Market Data Fees January 8, 2010. I. Introduction On November 25, 2009, the International...

  15. 76 FR 64980 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed...

    Science.gov (United States)

    2011-10-19

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65548; File No. SR-ISE-2011-39] Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed Rule Change Relating to Complex Orders October 13, 2011. I. Introduction On July 1, 2011, the International Securities Exchange...

  16. 77 FR 4852 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed...

    Science.gov (United States)

    2012-01-31

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66234; File No. SR-ISE-2011-82] Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed Rule Change Relating to Legging Orders January 25, 2012. I. Introduction On November 29, 2011, the International Securities...

  17. International Conference on Effective Nuclear Regulatory Systems: Sustaining Improvements Globally. Book of Abstracts

    International Nuclear Information System (INIS)

    2016-01-01

    The objective of this conference is to review and assess ways of further improving the effectiveness of regulatory systems for nuclear facilities and activities for both nuclear safety and nuclear security. The action items in the summary presented by the President of the conference held in 2013 in Ottawa, the lessons of the Fukushima Daiichi accident, the discussions at other international conferences and at international experts’ meetings conducted within the framework of the IAEA Action Plan on Nuclear Safety, as well as the CNS and the principles outlined in the Vienna Declaration on Nuclear Safety, will continue to have a significant impact on regulatory systems. All the aforementioned need to be taken into account to sustain improvements to regulatory systems. The expected outcomes of the conference are: - Enhanced safety and security of nuclear installations worldwide; - Challenges in regulating radiation sources and radioactive waste addressed; - Enhanced international cooperation for sustaining regulatory effectiveness; - Strengthened and sustained regulatory competence for nuclear safety and security; and - Strategies and actions for the future identified, as well as issues for consideration by governments, regulatory bodies and international organizations.

  18. Relative efficacy of drugs: an emerging issue between regulatory agencies and third-party payers.

    Science.gov (United States)

    Eichler, Hans-Georg; Bloechl-Daum, Brigitte; Abadie, Eric; Barnett, David; König, Franz; Pearson, Steven

    2010-04-01

    Drug regulatory agencies have traditionally assessed the quality, safety and efficacy of drugs, and the current paradigm dictates that a new drug should be licensed when the benefits outweigh the risks. By contrast, third-party payers base their reimbursement decisions predominantly on the health benefits of the drug relative to existing treatment options (termed relative efficacy; RE). Over the past decade, the role of payers has become more prominent, and time-to-market no longer means time-to-licensing but time-to-reimbursement. Companies now have to satisfy the sometimes divergent needs of both regulators and payers, and to address RE during the pre-marketing stages. This article describes the current political background to the RE debate and presents the scientific and methodological challenges as they relate to RE assessment. In addition, we explain the impact of RE on drug development, and speculate on future developments and actions that are likely to be required from key players.

  19. Impact of regulatory guidances and drug regulation on risk minimization interventions in drug safety: a systematic review.

    Science.gov (United States)

    Nkeng, Lenhangmbong; Cloutier, Anne-Marie; Craig, Camille; Lelorier, Jacques; Moride, Yola

    2012-07-01

    Therapeutic risk management has received growing interest in recent years, particularly since the publication of regulatory guidances in 2005 and 2006, paralleled with a change in drug regulation. The characteristics of risk minimization interventions (RMIs) that have been implemented or approved remain inadequately explored. The aim of this study was to review RMIs published in the literature or posted on regulatory agency websites over the past 10 years, and to assess whether publication of regulatory guidances on risk management is associated with changes in the number and types of interventions. Sources were searched for RMIs published/posted between 1 January 2000 and 31 December 2009. For the literature search, MEDLINE and EMBASE databases were used using key words related to drug safety (i.e. 'drug toxicity') and the individual RMI names. The website review involved searches of major regulatory authority websites such as the European Medicines Agency, US FDA, Health Canada, the UK's Medicines and Healthcare products Regulatory Agency, Japan's Pharmaceutical and Medical Devices Agency and Australia's Therapeutic Goods Administration. The following eligibility criteria were applied for inclusion in the review: published/posted between the years 2000 and 2009, inclusive; involving drug products; use in humans; and involving RMIs, or tools used to increase the reporting of adverse events (AEs). Natural healthcare products, devices, diagnostic chemicals, pregnancy registries without follow-up, medication errors and products not used as therapy for illness were not retained. For each source, the following characteristics were extracted: nature of the intervention, target population, therapeutic area, AE(s) of special interest, country/regulatory agency and year of publication. A total of 119 unique interventions were identified in the literature (54 published in 2000-4 and 65 published in 2005-9). Interventions included educational material (n = 37; 31%), black

  20. Rethinking 'flexibilities' in the international drug control system-Potential, precedents and models for reforms.

    Science.gov (United States)

    Collins, John

    2017-01-24

    Much international drug policy debate centres on, what policies are permissible under the international drug treaties, whether member states are openly 'breaching' these treaties by changing national regulatory frameworks and shifting priorities away from a 'war on drugs' approach, and what 'flexibility' exists for policy reform and experimentation at national and local levels. Orthodox interpretations hold that the current system is a US-led 'prohibition regime' that was constructed in an extremely repressive and restrictive manner with almost no flexibility for significant national deviations. This paper challenges these orthodox interpretive frameworks and suggests no absolute and clear dichotomy between strict adherence and 'breaches' of the international treaties. This paper uses historical analysis to highlight the flaws in orthodox policy analyses, which assume a uniform interpretation, implementation and set of policy trajectories towards a 'prohibition regime' in the 20th century. It challenges some existing legal interpretations of the treaties through recourse to historical precedents of flexible interpretation and policy prioritisation. It then examines the legal justifications currently being formulated by member states to explain a shift towards policies which, until recently, have been viewed as outside the permissible scope of the conventions. It then examines a functionalist framework for understanding the likely contours of drug diplomacy in the post-UN General Assembly Special Session (UNGASS) 2016 era. The paper highlights that, contrary to current policy discourses, the international control system has always been implemented in a 'flexible' manner. It demonstrates that drug control goals were repeatedly subsumed to security, development, political stability and population welfare imperatives, or what we might now refer to under the umbrella of 'development issues.' The paper further demonstrates that policy prioritisation, inherent treaty

  1. Regulatory scientific advice in drug development: does company size make a difference?

    Science.gov (United States)

    Putzeist, Michelle; Mantel-Teeuwisse, Aukje K; Gispen-De Wied, Christine C; Hoes, Arno W; Leufkens, Hubert G

    2011-02-01

    To assess whether the content of Scientific Advice (SA) questions addressed to a national drug regulatory agency is associated with company size. This may help to increase understanding about the knowledge, strategic, and regulatory gaps companies face during drug development. A cross-sectional analysis was performed of SA provided by the Dutch Medicines Evaluation Board (MEB) in 2006-2008. Definition of company size was based on ranking by total revenues (Scrip's Pharmaceutical Company League Tables 2008). The content of each SA question was scored according to predefined domains (quality, nonclinical, clinical, regulatory, and product information), their subdomains (e.g., efficacy), and a selection of additional content variables (e.g., endpoints, choice of active comparator). In total, 201 SA documents including 1,087 questions could be identified. Small, medium-sized, and large companies asked for SA 110 (54.7%), 40 (19.9%), and 51 (25.4%) times, respectively. Clinical questions were asked most often (65.9%), mainly including efficacy (33.2%) and safety questions (24.0%). The most frequent topics were overall efficacy and safety strategy. Small companies asked quality and nonclinical questions more often (P companies (P = 0.004). Small companies asked significantly more clinical questions about pharmacokinetics, including bioequivalence, than medium-sized and large companies (P Company size is associated with the content of SA questions. MEB advice accommodates both innovative and noninnovative drug development.

  2. Regulatory practices and standards: the international scene and trends

    International Nuclear Information System (INIS)

    Vinck, W.; Essler, W.; Maurer, H.A.; Reijen, G. van.

    1978-01-01

    At national level, codification of standards governing the licensing and operation of nuclear installations is very different, ranging from criteria to regulations, according to the degree of the obligation imposed by national authorities; it also reflects the variety of national situations and the peculiarities of the legal and political systems. The need to agree upon a level of nuclear safety which is generally recognised as satisfactory and to exchange scientific and technological information in this field has greatly stimulated international co-operation, in particular within the framework of specialized international organisations such as IAEA, ISO, Euratom and OECD/NEA. Harmonization of such standards is particularly important from the viewpoint of public opinion in the countries concerned. In addition, the intrinsic safety of nuclear power plants, assurances as to the duration of plant life should increasingly be highlighted in future. (NEA) [fr

  3. Genome-wide discovery of drug-dependent human liver regulatory elements.

    Directory of Open Access Journals (Sweden)

    Robin P Smith

    2014-10-01

    Full Text Available Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed RNA-seq and ChIP-seq using antibodies against the pregnane X receptor (PXR and three active regulatory marks (p300, H3K4me1, H3K27ac on primary human hepatocytes treated with rifampin or vehicle control. Rifampin and PXR were chosen since they are part of the CYP3A4 pathway, which is known to account for the metabolism of more than 50% of all prescribed drugs. We selected 227 proximal promoters for genes with rifampin-dependent expression or nearby PXR/p300 occupancy sites and assayed their ability to induce luciferase in rifampin-treated HepG2 cells, finding only 10 (4.4% that exhibited drug-dependent activity. As this result suggested a role for distal enhancer modules, we searched more broadly to identify 1,297 genomic regions bearing a conditional PXR occupancy as well as all three active regulatory marks. These regions are enriched near genes that function in the metabolism of xenobiotics, specifically members of the cytochrome P450 family. We performed enhancer assays in rifampin-treated HepG2 cells for 42 of these sequences as well as 7 sequences that overlap linkage-disequilibrium blocks defined by lead SNPs from pharmacogenomic GWAS studies, revealing 15/42 and 4/7 to be functional enhancers, respectively. A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity. Combined, our results further suggest that enhancers are the predominant targets of rifampin-induced PXR activation, provide a genome-wide catalog of PXR targets and serve as a model for the identification of drug-responsive regulatory elements.

  4. Legislative/regulatory drivers the international maritime organization

    International Nuclear Information System (INIS)

    Wallace, S.A.

    1992-01-01

    I am pleased and honored to be here representing the International Maritime Organization (IMO), which is the cosponsor of this R ampersand D Forum with the Coast Guard. This is truly an international Forum - and it needs to be. I should like to turn now to the subject of IMO and, for the benefit of many here who do not know the Organization, describe very briefly what IMO is and what it does. IMO is the specialized agency of the United Nations that deals with shipping matters. The Organization has 136 member-states and its headquarters is located in London on the bank of the Thames River. It has a permanent secretariat numbering about 300 international civil servants, headed by the Secretary-General. IMO is a technical organization, and it conducts its work through committees of the whole, with the help of standing subcommittees, working groups, and other groups or bodies formed as the need arises. We have with us today a representative of MED in the person of Commander David Pascoe, whom the U.S. Coast Guard has seconded to IMO for a two-year tour of duty. The purposes of IMO are, in short, to improve safety at sea and to prevent pollution from ships; i.e., IMO continuously strives for safer ships and cleaner oceans. IMO also promotes technical cooperation and assistance, particularly among developing countries, to help satisfy these purposes globally. The work product of IMO includes more than 30 multilateral treaties and 600 codes and sets of recommendations on maritime safety, marine environment protection, and other legal and technical issues involving worldwide shipping

  5. Comparative study of Malaysian and Philippine regulatory infrastructures on radiation and nuclear safety with international standards

    International Nuclear Information System (INIS)

    Cayabo, Lynette B.

    2013-06-01

    This study presents the results of the critical reviews, analysis, and comparison of the regulatory infrastructures for radiation and nuclear safety of Malaysis and the Philippines usi ng the IAEA safety requirements, GSR Part 1, G overnment, Legal and Regulatory Framework for Safety'' as the main basis and in part, the GSR Part 3, R adiation Protection and Safety of Radiation Sources: International Basic Safety Standards . The scope of the comparison includes the elements of the relevant legislations, the regulatory system and processes including the core functions of the regulatory body (authorization, review and assessment, inspection and enforcement, development of regulations and guides); and the staffing and training of regulatory body. The respective availabe data of the Malaysian and Philippine regulatory infrastructures and current practices were gathered and analyzed. Recommendations to fill the gaps and strengthen the existing regulatory infrastructure of each country was given using as bases relevant IAEA safety guides. Based on the analysis made, the main findings are: the legislations of both countries do not contain al the elements of teh national policy and strategy for safety as well as those of teh framework for safety in GR Part I. Among the provision that need to be included in the legislations are: emergency planning and response; decommissioning of facilities safe management of radioactive wastes and spent fuel; competence for safety; and technical sevices. Provisions on coordination of different authorities with safety responsibilities within the regulatory framework for safety as well as liaison with advisory bodies and support organizations need to be enhanced. The Philippines needs to establish an independent regulatory body, ie. separate from organizations charged with promotion of nuclear technologies and responsible for facilitiesand activities. Graded approach on the system of notification and authorization by registration and

  6. Regulatory changes to renewable energy support schemes: An international investment law perspective

    OpenAIRE

    Paleckaite, Gintare

    2014-01-01

    Thesist analyzes how regulatory changes related to renewable energy investment support schemes can be perceived under international investment law standards and how possible decisions of international investment law tribunals could impact investment in this sector. This research is based on case studies of two states: Spain and the Czech Republic and claims against them. These cases will assist in analyzing the effects of the amendment/revocation of renewable energy support schemes. Answers t...

  7. 77 FR 15417 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

    Science.gov (United States)

    2012-03-15

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66566; File No. SR-ISE-2012-21] Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of Proposed Rule Change Relating to a... Ownership Interest in ISE Holdings, Inc. to a Newly Formed Swiss Corporation, Eurex Global Derivatives AG...

  8. 78 FR 6155 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and...

    Science.gov (United States)

    2013-01-29

    ... virtually impossible for any exchange to identify, and thus assess fees such as an ORF on, each executing... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68711; File No. SR-MIAX-2013-01] Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and Immediate...

  9. International principles for exemption from regulatory control and their application to waste management

    International Nuclear Information System (INIS)

    Linsley, G.S.

    1989-01-01

    This paper describes the main features of the international consensus on principles for exempting radiation sources and practices from regulatory control reached at a meeting in Vienna in March 1988. Some remaining problems, both of a philosophical and technical nature especially related to the application of the principles to radioactive waste disposal, are discussed

  10. International trends in admissions and drug sales for asthma.

    Science.gov (United States)

    Gupta, R; Anderson, H R; Strachan, D P; Maier, W; Watson, L

    2006-02-01

    To test whether national patterns of asthma drug use, particularly inhaled corticosteroids (ICS), are related to the rate of acute severe asthma exacerbations. The relation of international trends in hospital admissions for asthma with asthma drug sales was examined using country-specific regressions over the period 1990-1999. Pooled estimates of the regression coefficients were calculated using random effects models. Data on asthma admissions and asthma drug sales (including the sub-category ICS) were obtained from 11 countries. There was a negative relationship between falling admissions and rising sales of respiratory drugs and ICS in 9 of these 11 countries. A pooled estimate of the change in asthma admission rate per 10,000 associated with a unit increase in sales rate was -6.3 (95% CI -10.4 - -2.3) for all asthma drugs and -11.2 (95% CI -19.7 - -2.8) for ICS. At the national level, there is good evidence that over the last decade, increased sales of asthma drugs, and ICS in particular, were associated with a decline in rates of hospital admission for asthma. This is consistent with a beneficial effect of increasing use of asthma drugs, but other explanations such as decreasing prevalence could also be responsible.

  11. Application of omics data in regulatory toxicology: report of an international BfR expert workshop.

    Science.gov (United States)

    Marx-Stoelting, P; Braeuning, A; Buhrke, T; Lampen, A; Niemann, L; Oelgeschlaeger, M; Rieke, S; Schmidt, F; Heise, T; Pfeil, R; Solecki, R

    2015-11-01

    Advances in omics techniques and molecular toxicology are necessary to provide new perspectives for regulatory toxicology. By the application of modern molecular techniques, more mechanistic information should be gained to support standard toxicity studies and to contribute to a reduction and refinement of animal experiments required for certain regulatory purposes. The relevance and applicability of data obtained by omics methods to regulatory purposes such as grouping of chemicals, mode of action analysis or classification and labelling needs further improvement, defined validation and cautious expert judgment. Based on the results of an international expert workshop organized 2014 by the Federal Institute for Risk Assessment in Berlin, this paper is aimed to provide a critical overview of the regulatory relevance and reliability of omics methods, basic requirements on data quality and validation, as well as regulatory criteria to decide which effects observed by omics methods should be considered adverse or non-adverse. As a way forward, it was concluded that the inclusion of omics data can facilitate a more flexible approach for regulatory risk assessment and may help to reduce or refine animal testing.

  12. Consumer's risk in the EMA and FDA regulatory approaches for bioequivalence in highly variable drugs.

    Science.gov (United States)

    Muñoz, Joel; Alcaide, Daniel; Ocaña, Jordi

    2016-05-30

    The 2010 US Food and Drug Administration and European Medicines Agency regulatory approaches to establish bioequivalence in highly variable drugs are both based on linearly scaling the bioequivalence limits, both take a 'scaled average bioequivalence' approach. The present paper corroborates previous work suggesting that none of them adequately controls type I error or consumer's risk, so they result in invalid test procedures in the neighbourhood of a within-subject coefficient of variation osf 30% for the reference (R) formulation. The problem is particularly serious in the US Food and Drug Administration regulation, but it is also appreciable in the European Medicines Agency one. For the partially replicated TRR/RTR/RRT and the replicated TRTR/RTRT crossover designs, we quantify these type I error problems by means of a simulation study, discuss their possible causes and propose straightforward improvements on both regulatory procedures that improve their type I error control while maintaining an adequate power. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Understanding the relative roles of pharmacogenetics and ontogeny in pediatric drug development and regulatory science.

    Science.gov (United States)

    Leeder, J Steven; Kearns, Gregory L; Spielberg, Stephen P; van den Anker, John

    2010-12-01

    Understanding the dose-exposure-response relationship across the pediatric age spectrum from preterm and term newborns to infants, children, adolescents, and adults is a major challenge for clinicians, pharmaceutical companies, and regulatory agencies. Over the past 3 decades, clinical investigations of many drugs commonly used in pediatric therapeutics have provided valuable insights into age-associated differences in drug disposition and action. However, our understanding of the contribution of genetic variation to variability in drug disposition and response in children generally has lagged behind that of adults. This article proposes a systematic approach that can be used to assess the relative contributions of ontogeny and genetic variation for a given compound. Application of the strategy is illustrated using the current regulatory dilemma posed by the safety and effectiveness of over-the-counter cough and cold remedies as an example. The results of the analysis can be used to aid in the design of studies to yield maximally informative data in pediatric populations of different ages and developmental stages and thereby improve the efficiency of study design.

  14. An international comparison of regulatory organizations and licensing procedures for new nuclear power plants

    International Nuclear Information System (INIS)

    Bredimas, Alexandre; Nuttall, William J.

    2008-01-01

    This paper considers measures needed to license new nuclear power plants efficiently. We base our analysis on international standards and a comparison of the national regulatory and licensing framework in seven countries (Canada, France, Germany, Japan, Switzerland, the UK and the USA). We split the review into the organization of regulatory responsibilities and the licensing process. We propose a set of considerations that should be incorporated into national solutions. While conscious of the different cultural fundamentals of each region, we hope this paper will help fuel an emerging debate on this highly topical issue

  15. Regulatory volume decrease in Leishmania mexicana: effect of anti-microtubule drugs

    Directory of Open Access Journals (Sweden)

    Francehuli Dagger

    2013-02-01

    Full Text Available The trypanosomatid cytoskeleton is responsible for the parasite's shape and it is modulated throughout the different stages of the parasite's life cycle. When parasites are exposed to media with reduced osmolarity, they initially swell, but subsequently undergo compensatory shrinking referred to as regulatory volume decrease (RVD. We studied the effects of anti-microtubule (Mt drugs on the proliferation of Leishmania mexicana promastigotes and their capacity to undergo RVD. All of the drugs tested exerted antiproliferative effects of varying magnitudes [ansamitocin P3 (AP3> trifluoperazine > taxol > rhizoxin > chlorpromazine]. No direct relationship was found between antiproliferative drug treatment and RVD. Similarly, Mt stability was not affected by drug treatment. Ansamitocin P3, which is effective at nanomolar concentrations, blocked amastigote-promastigote differentiation and was the only drug that impeded RVD, as measured by light dispersion. AP3 induced 2 kinetoplasts (Kt 1 nucleus cells that had numerous flagella-associated Kts throughout the cell. These results suggest that the dramatic morphological changes induced by AP3 alter the spatial organisation and directionality of the Mts that are necessary for the parasite's hypotonic stress-induced shape change, as well as its recovery.

  16. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  17. Regulatory aspects of teratology: role of the Food and Drug Administration

    International Nuclear Information System (INIS)

    Kelsey, F.O.

    1982-01-01

    The Food and Drug Administration is a scientific regulatory agency whose consumer protection activities cover a wide range of products including foods and additives, and pesticide residues on foods; drugs; cosmetics; medical devices; and radiation-emitting electronic products. Amongst its concerns is the possible teratogen effects of regulated products to which the pregnant woman is exposed. The policies and programs of the agency directed toward reducing such risks to the unborn are reviewed. These measures include guidelines for animal reproduction studies and for clinical trials involving women to childbearing potential; labeling of products to disclose known or possible harm to the fetus or embryo; surveillance procedures designed to detect previously unsuspected adverse effects of marketed products; research activities designed to develop better understanding of developmental toxicology and improved techniques for detecting embryocidal and embryotoxic effects; and educational efforts directed both to professionals and the public regarding hazards to the unborn of agency-regulated products

  18. Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

    Science.gov (United States)

    Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

    2016-11-01

    This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

  19. Risk perception of prescription drugs: results of a survey among experts in the European regulatory network.

    Science.gov (United States)

    Beyer, Andrea R; Fasolo, Barbara; Phillips, Lawrence D; de Graeff, Pieter A; Hillege, Hans L

    2013-05-01

    Experts are perceived to be veridical and to focus only on objective data when evaluating risk. Only a few research studies have attempted to characterize the subjectivity in risk evaluation among experts. The hypothesis of this study is that expert evaluation of a pharmaceutical drug can be partly explained by dimensions that describe the drug and by individual characteristics. Seventy-five medical assessors in 9 EU countries evaluated a list of 28 pharmaceutical drugs using 4 scales: risk, benefit, seriousness of harm, and patients' knowledge of the risk. They were also given a mock "clinical dossier" and asked to rate it on 8 dimensions: risk, benefit, worry, magnitude of the exposure, scientific knowledge of the risk, familiarity of the risk, ethical concerns, and risk acceptability. Female assessors perceived significantly higher benefits than men for a large number of the 28 drugs. Principal component analysis of the ratings for the clinical dossiers revealed 2 underlying components: seriousness of harm and scientific evidence. A regression model predicting the risk perception of the drug showed that the variables seriousness of harm (benefit, worry, magnitude of exposure, ethical concerns, and risk acceptability), years of regulatory experience, gender, and type of drug explained 54% of the variability among assessors. Assessors' view of the risks associated with pharmaceutical drugs is influenced by worry for patient safety, magnitude of patient exposure, and ethical concerns. These dimensions may influence their perceptions of benefit and risk acceptability. Senior assessors are more risk averse than junior assessors, and female assessors seem to be sensitive to the promise of benefit from medicines and consequently may be less risk averse than male assessors.

  20. International Nuclear Safety Experts Conclude IAEA Peer Review of Korea's Regulatory System

    International Nuclear Information System (INIS)

    2011-01-01

    Full text: An international team of senior nuclear safety experts concluded today a two-week mission to review the regulatory framework for nuclear safety in the Republic of Korea. The team identified good practices and gave advice on areas for future improvements. The IAEA has conveyed the team's main conclusions to the Government of Korea, while the final report will be submitted by the end of summer 2011. At the request of the Korean Government, the IAEA assembled a team of 16 senior regulatory experts from 14 nations to conduct the Integrated Regulatory Review Service (IRRS) mission involving the Korean Ministry for Education, Science and Technology (MEST) and the Korean Institute for Nuclear Safety (KINS). The mission is a peer-review based on the IAEA Safety Standards. ''This was the first IRRS mission organized after Japan's Fukushima Daiichi nuclear accident and it included a review of the regulatory implications of that event,' explains Denis Flory, IAEA Deputy Director General and Head of the Department of Nuclear Safety and Security. William Borchardt, Executive Director of Operations from the US Nuclear Regulatory Commission and Team Leader of this mission commended the Korean authorities for their openness and commitment to sharing their experience with the world's nuclear safety community. ''IRRS missions such as the one that was just concluded here in the Republic of Korea are crucial to the enhancement of nuclear safety worldwide,'' he said. The IRRS team reviewed Korea's current regulatory framework while acknowledging the fact that the country's Government has already decided to establish, as of October 2011, a new independent regulatory body to be called Nuclear Safety Commission (NSC). As a consequence, KINS role will be as a regulatory expert organization reporting to the NSC, while MEST's role will be restricted to promoting the utilization of nuclear energy. The IRRS team identified particular strengths in the Korean regulatory system

  1. International Nuclear Safety Experts Conclude IAEA Peer Review of Swiss Regulatory Framework

    International Nuclear Information System (INIS)

    2011-01-01

    Full text: A team of international nuclear safety experts today completed a two-week International Atomic Energy Agency (IAEA) review of the regulatory framework for nuclear safety in Switzerland. The Integrated Regulatory Review Service (IRRS) mission noted good practices in the Swiss system and also made recommendations for the nation's nuclear regulatory authority, the Swiss Federal Nuclear Safety Inspectorate (ENSI). ''Our team developed a good impression of the independent Swiss regulator - ENSI - and the team considered that ENSI deserves particular credit for its actions to improve Swiss safety capability following this year's nuclear accident in Japan,'' said IRRS Team Leader Jean-Christophe Niel of France. The mission's scope covered the Swiss nuclear regulatory framework for all types of nuclear-related activities regulated by ENSI. The mission was conducted from 20 November to 2 December, mainly at ENSI headquarters in Brugg. The team held extensive discussions with ENSI staff and visited many Swiss nuclear facilities. IRRS missions are peer reviews, not inspections or audits, and are conducted at the request of host nations. For the Swiss review, the IAEA assembled a team of 19 international experts from 14 countries. The experts came from Belgium, Brazil, the Czech Republic, Finland, France, Germany, Italy, the Republic of Korea, Norway, Russia, Slovakia, Sweden, the United Kingdom, and the United States. ''The findings of the IRRS mission will help us to further improve our work. That is part of our safety culture,'' said ENSI Director General Hans Wanner. ''As Switzerland argued at international nuclear safety meetings this year for a strengthening of the international monitoring of nuclear power, we will take action to fulfil the recommendations.'' The IRRS team highlighted several good practices of the Swiss regulatory system, including the following: ENSI requires Swiss nuclear operators to back-fit their facilities by continuously upgrading

  2. International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

    Science.gov (United States)

    Bal-Price, Anna; Crofton, Kevin M; Leist, Marcel; Allen, Sandra; Arand, Michael; Buetler, Timo; Delrue, Nathalie; FitzGerald, Rex E; Hartung, Thomas; Heinonen, Tuula; Hogberg, Helena; Bennekou, Susanne Hougaard; Lichtensteiger, Walter; Oggier, Daniela; Paparella, Martin; Axelstad, Marta; Piersma, Aldert; Rached, Eva; Schilter, Benoît; Schmuck, Gabriele; Stoppini, Luc; Tongiorgi, Enrico; Tiramani, Manuela; Monnet-Tschudi, Florianne; Wilks, Martin F; Ylikomi, Timo; Fritsche, Ellen

    2015-02-01

    A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.

  3. Cancer Drugs: An International Comparison of Postlicensing Price Inflation.

    Science.gov (United States)

    Savage, Philip; Mahmoud, Sarah; Patel, Yogin; Kantarjian, Hagop

    2017-06-01

    The cost of cancer drugs forms a rising proportion of health care budgets worldwide. A number of studies have examined international comparisons of initial cost, but there is little work on postlicensing price increases. To examine this, we compared cancer drug prices at initial sale and subsequent price inflation in the United States and United Kingdom and also reviewed relevant price control mechanisms. The 10 top-selling cancer drugs were selected, and their prices at initial launch and in 2015 were compared. Standard nondiscounted prices were obtained from the relevant annual copies of the RED BOOK and the British National Formulary. At initial marketing, prices were on average 42% higher in the United States than in the United Kingdom. After licensing in the United States, all 10 drugs had price rises averaging an overall annual 8.8% (range, 1.4% to 24.1%) increase. In comparison, in the United Kingdom, six drugs had unchanged prices, two had decreased prices, and two had modest price increases. The overall annual increase in the United Kingdom was 0.24%. Cancer drug prices are rising substantially, both at their initial marketing price and, in the United States, at postlicensing prices. In the United Kingdom, the Pharmaceutical Price Regulation Scheme, an agreement between the government and the pharmaceutical industry, controls health care costs while allowing a return on investment and funds for research. The increasing costs of cancer drugs are approaching the limits of sustainability, and a similar government-industry agreement may allow stability for both health care provision and the pharmaceutical industry in the United States.

  4. International nuclear safety experts complete IAEA peer review of German regulatory system

    International Nuclear Information System (INIS)

    2008-01-01

    Full text: An international expert team has today completed a two-week IAEA review of Germany's nuclear regulatory system. The team identified good practices within the system and gave advice on some areas for further improvement. The IAEA has conveyed the initial findings to German authorities but the final report will be submitted within two months. At the request of the Government of the Federal Republic of Germany, the International Atomic Energy Agency (IAEA) assembled a team of 14 experts to conduct an Integrated Regulatory Review Service (IRRS) mission. This is a peer review based on IAEA Standards. It is not an inspection, nor an audit. The scope of the mission was limited to the safety regulation of nuclear power plants. Experts from Canada, the Czech Republic, Finland, France, Japan, the Netherlands, Republic of Korea, Spain, Switzerland, the UK, the US and from the IAEA took part in the mission, which was conducted from 7 to 19 September in Bonn, Stuttgart and Berlin. The main basis for the review was a well-prepared self-assessment made by the Federal Ministry of Environment, Nature Conservation and Nuclear Safety (BMU) and the Ministry of Environment of the federal state of Baden-Wuerttemberg (UM BW). 'The team members were impressed by the extensive preparation and dedication of the staff both at BMU and UM BW to excellence in nuclear safety,' said Mike Weightman, IRRS Team Leader and Chief Inspector of the UK nuclear regulatory body, the Nuclear Directorate of the Health and Safety Executive. 'We hope the IRRS mission will facilitate further improvements in the safety regulation of nuclear power in Germany and throughout the world.' 'Germany's invitation to undergo such a detailed review is a clear demonstration of its openness and commitment to continuously improve nuclear safety regulation,' said Philippe Jamet, Director of the IAEA's Nuclear Installation Safety Division. Among the particular strengths of BMU and UM BW associated with their

  5. Strategic Regulatory Evaluation and Endorsement of the Hollow Fiber Tuberculosis System as a Novel Drug Development Tool.

    Science.gov (United States)

    Romero, Klaus; Clay, Robert; Hanna, Debra

    2015-08-15

    The first nonclinical drug development tool (DDT) advanced by the Critical Path to TB Drug Regimens (CPTR) Initiative through a regulatory review process has been endorsed by leading global regulatory authorities. DDTs with demonstrated predictive accuracy for clinical and microbiological outcomes are needed to support decision making. Regulatory endorsement of these DDTs is critical for drug developers, as it promotes confidence in their use in Investigational New Drug and New Drug Application filings. The in vitro hollow fiber system model of tuberculosis (HFS-TB) is able to recapitulate concentration-time profiles (exposure) observed in patients for single drugs and combinations, by evaluating exposure measures for the ability to kill tuberculosis in different physiologic conditions. Monte Carlo simulations make this quantitative output useful to inform susceptibility breakpoints, dosage, and optimal combination regimens in patients, and to design nonclinical experiments in animal models. The Pre-Clinical and Clinical Sciences Working Group within CPTR executed an evidence-based evaluation of the HFS-TB for predictive accuracy. This extensive effort was enabled through the collaboration of subject matter experts representing the pharmaceutical industry, academia, product development partnerships, and regulatory authorities including the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). A comprehensive analysis plan following the regulatory guidance documents for DDT qualification was developed, followed by individual discussions with the FDA and the EMA. The results from the quantitative analyses were submitted to both agencies, pursuing regulatory DDT endorsement. The EMA Qualification Opinion for the HFS-TB DDT was published 26 January 2015 (available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000319.jsp). © The Author 2015. Published by Oxford University Press on behalf of the

  6. Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic.

    Science.gov (United States)

    Meyskens, Frank L; Curt, Gregory A; Brenner, Dean E; Gordon, Gary; Herberman, Ronald B; Finn, Olivera; Kelloff, Gary J; Khleif, Samir N; Sigman, Caroline C; Szabo, Eva

    2011-03-01

    This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high(er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs.

  7. International Expert Team Concludes IAEA Peer Review of Poland's Regulatory Framework for Nuclear and Radiation Safety

    International Nuclear Information System (INIS)

    2013-01-01

    Full text: International safety experts last week concluded a two-week International Atomic Energy Agency (IAEA) mission to review the regulatory framework for nuclear and radiation safety in Poland. In its preliminary report, the Integrated Regulatory Review Service (IRRS) mission team found that Poland's nuclear regulator, Panstwowa Agencja Atomistyki (PAA), has a clear commitment to safety, a high level of transparency, competent staff and leadership, and a good recognition of challenges ahead related to Poland's efforts to develop nuclear power. ''Poland's regulatory framework and the work of PAA give high confidence of strong radiation protection for the Polish people. Further, there has been significant progress in the development of Poland's regulatory framework in preparation for the challenge of regulating nuclear power,'' said team leader Robert Lewis, a senior executive in the US Nuclear Regulatory Commission. The mission was conducted at the request of the Government of Poland from 15-25 April. The team was made up of 11 regulatory experts from Belgium, the Czech Republic, Finland, France, the Republic of Korea, Slovakia, Slovenia, Sweden, the United Arab Emirates, the United Kingdom and the United States, as well as five IAEA staff members. The IRRS review team was very thorough in its review, and we welcome its advice on how to continue to improve our programmes to protect people and the environment , said Janusz Wlodarski, President of PAA. The team interviewed members of PAA and officials from various ministries, as well as key players in the Polish safety framework. Such IRRS missions are peer reviews based on IAEA Safety Standards, not inspections or audits. Among its main observations the IRRS review team identified the following good practices: Applying the considerable experience of PAA's senior management to regulatory issues; The introduction of changes to Poland's laws and regulations following broad public consultation at an early stage in

  8. Analytical challenges and regulatory requirements for nasal drug products in europe and the u.s.

    Science.gov (United States)

    Trows, Sabrina; Wuchner, Klaus; Spycher, Rene; Steckel, Hartwig

    2014-04-11

    Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results.

  9. Chinese proprietary medicine in Singapore: regulatory control of toxic heavy metals and undeclared drugs.

    Science.gov (United States)

    Koh, H L; Woo, S O

    2000-11-01

    Traditional Chinese medicine (TCM) is gaining popularity as a form of complementary and alternative medicine. Reports of efficacy of TCM are increasing in numbers. TCM includes both crude Chinese medicinal materials (plants, animal parts and minerals) and Chinese proprietary medicine (CPM) [final dosage forms]. Despite the belief that CPM and herbal remedies are of natural origin, unlike Western medicine, and are hence safe and without many adverse effects, there have been numerous reports of adverse effects associated with herbal remedies. Factors affecting the safety of herbal medicines include intrinsic toxicity, adulteration, substitution, contamination, misidentification, lack of standardisation, incorrect preparation and/or dosage and inappropriate labelling and/or advertising. Hence, new regulations on the control of CPM were enforced in Singapore with effect from 1 September 1999. These include licensing and labelling requirements, as well as control of microbial contamination. This article also reviews reports of excessive toxic heavy metals and undeclared drugs in CPM in Singapore between 1990 and 1997. The names, uses, toxic heavy metal or drug detected and the year of detection are tabulated. Information on the brand or manufacturer's name are provided whenever available. The public and healthcare professionals should be better informed of the basic concept of TCM and its usefulness, as well as the potential adverse effects associated with its use. Greater control over the safety and quality of CPM could be achieved through good manufacturing practice, regulatory control, research, education, reporting usage of Chinese medicine (as in drug history) as well as reporting of adverse events.

  10. Utilizing national and international registries to enhance pre-market medical device regulatory evaluation.

    Science.gov (United States)

    Yue, Lilly Q; Campbell, Gregory; Lu, Nelson; Xu, Yunling; Zuckerman, Bram

    2016-01-01

    Regulatory decisions are made based on the assessment of risk and benefit of medical devices at the time of pre-market approval and subsequently, when post-market risk-benefit balance needs reevaluation. Such assessments depend on scientific evidence obtained from pre-market studies, post-approval studies, post-market surveillance studies, patient perspective information, as well as other real world data such as national and international registries. Such registries provide real world evidence and are playing a more and more important role in enhancing the safety and effectiveness evaluation of medical devices. While these registries provide large quantities of data reflecting real world practice and can potentially reduce the cost of clinical trials, challenges arise concerning (1) data quality adequate for regulatory decision-making, (2) bias introduced at every stage and aspect of study, (3) scientific validity of study designs, and (4) reliability and interpretability of study results. This article will discuss related statistical and regulatory challenges and opportunities with examples encountered in medical device regulatory reviews.

  11. International nuclear safety experts conclude IAEA peer review of China's regulatory system

    International Nuclear Information System (INIS)

    2010-01-01

    Full text: An international team of senior experts on nuclear safety regulation today completed a two-week International Atomic Energy Agency (IAEA) review of the governmental and regulatory framework for nuclear safety in the People's Republic of China. The team identified good practices within the system and gave advice on areas for future improvements. The IAEA has conveyed the team's main conclusions to the Government of the People's Republic of China. The final report will be submitted to China by Autumn 2010. At the request of Chinese authorities, the IAEA assembled a team of 22 experts to conduct an Integrated Regulatory Review Service (IRRS) mission. This mission is a peer review based on the IAEA Safety Standards . It is not an inspection, nor an audit. The experts came from 15 different countries: Australia, Canada, the Czech Republic, Finland, France, Hungary, Japan, Pakistan, the Republic of Korea, Slovenia, South Africa, Sweden, the United Kingdom, Ukraine and the United States. Mike Weightman, the United Kingdom's Head of Nuclear Directorate, HSE and HM Chief Inspector of Nuclear Installations said: ''I was honoured and pleased to lead such a team of senior regulatory experts from around the world, and I was impressed by their commitment, experience and hard work to provide their best advice possible. We had very constructive interactions with the Chinese authority to maximize the beneficial impact of the mission.'' The scope of the mission included the regulation of nuclear and radiation safety of the facilities and activities regulated by the Ministry of Environmental Protection (MEP) National Nuclear Safety Administration (NNSA). The mission was conducted from 18 to 30 July, mainly in Beijing. To observe Chinese regulatory activities, the IRRS team visited several nuclear facilities, including a nuclear power plant, a manufacturer of safety components for nuclear power plants, a research reactor, a fuel cycle facility, a waste management facility

  12. International Nuclear and Radiation Safety Experts Conclude IAEA Peer Review of Slovenia's Regulatory System

    International Nuclear Information System (INIS)

    2011-01-01

    Full text: An international team of senior nuclear safety experts today concluded a 10-day mission to review the regulatory framework for nuclear and radiation safety in Slovenia. The team identified good practices and gave advice on areas for future improvements. The IAEA has conveyed the team's main conclusions to the Government of Slovenia and a final report will be submitted by the end of 2011. At the request of the Slovenian Government, the IAEA assembled a team of 10 senior regulatory experts from nine nations to conduct the Integrated Regulatory Review Service (IRRS) mission involving the Slovenian Nuclear Safety Administration (SNSA). The mission is a peer review based on the IAEA Safety Standards. Andrej Stritar, Director of Slovenian Nuclear Safety Administration, stressed ''how important it is for a small country like Slovenia to tightly follow international standards in the area of nuclear safety.'' He also expressed his gratitude to the IAEA, and the countries from which team members came, for their support and for their intensive work during the last ten days. Mission Team Leader Colin Patchett, Deputy Chief Inspector from the UK's Office for Nuclear Regulation commended ''the Slovenian authorities for their commitment to nuclear and radiation safety regulation and for sharing their experience.'' The IRRS team reviewed Slovenia's current regulatory framework and all SNSA-regulated facilities and activities, as well as the regulatory implications of the TEPCO Fukushima Daiichi accident. The IRRS team identified particular strengths in the Slovenian regulatory system, including: Through its legal framework, the Slovenian government has appointed SNSA to regulate its nuclear safety program and SNSA has in place an effective process for carrying out this responsibility; and Slovenia's response to the accident at the TEPCO Fukushima Daiichi power plant has been prompt and effective. Communications with the public, development of actions for improvement

  13. International Expert Team Concludes IAEA Peer Review of Bulgaria's Regulatory Framework for Nuclear and Radiation Safety

    International Nuclear Information System (INIS)

    2013-01-01

    Full text: An international team of senior nuclear safety and radiation protection experts today concluded a 12-day mission to review the regulatory framework for nuclear and radiation safety in Bulgaria. The Integrated Regulatory Review Service (IRRS) mission, conducted at the request of the Government of Bulgaria, identified a series of good practices and made recommendations to help enhance the overall performance of the regulatory system. IRRS missions, which were initiated in 2006, are peer reviews based on the IAEA Safety Standards; they are not inspections or audits. ''Bulgaria has a clear national policy and strategy for safety, which are well in line with international standards and practices and contribute to a high level of nuclear safety,'' said Mission Team Leader Marta Ziakova, Chairperson of the Nuclear Regulatory Authority of the Slovak Republic. The mission team, which conducted the review from 8 to 19 April, was made up of 16 senior regulatory experts from 16 nations, and six IAEA staff. ''The results of the IRRS mission will be valuable for the future development and reinforcement of the Bulgarian Nuclear Safety Agency (BNRA). The use of international standards and good practices helps to improve global harmonization in all areas of nuclear safety and radiation protection,'' said Sergey Tzotchev, Chairman of the BNRA. Among the main observations in its preliminary report, the IRRS mission team found that BNRA operates as an independent regulatory body and conducts its regulatory processes in an open and transparent manner. In line with the IAEA Action Plan on Nuclear Safety, the mission reviewed the regulatory implications for Bulgaria of the March 2011 accident at TEPCO's Fukushima Daiichi Nuclear Power Station in Japan. It found that the BNRA's response to the lessons learned from that accident was both prompt and effective. Strengths and good practices identified by the IRRS team include the following: A no-blame policy is enshrined in law for

  14. Regulatory Notes on Impact of Excipients on Drug Products and the Maillard Reaction.

    Science.gov (United States)

    Chowdhury, Dipak K; Sarker, Haripada; Schwartz, Paul

    2018-02-01

    In general, it is an important criterion that excipients remain inert throughout the shelf life of the formulated pharmaceutical product. However, depending on the functionality in chemical structure of active drug and excipients, they may undergo interaction. The well-known Maillard reaction occurs between a primary amine with lactose at high temperature to produce brown pigments. The reactivity of Maillard reaction may vary depending on the concentration as well as other conditions. Commercially, there are products where the active pharmaceutical ingredient is a primary amine and contains less than 75% lactose along with inactive excipients. This product does not show Maillard reaction during its shelf life of around 2 years at ambient conditions. However, when the same type of product contains more than 95 % lactose as an excipient, then there is a possibility of interactions though it is not visible in the initial year. Therefore, this regulatory note discusses involvement of different factors of a known drug-excipient interactions with case studies and provides an overview on how the concentration of lactose in the pharmaceutical product is important in addition to temperature and moisture in Maillard reaction.

  15. Drug policy and global regulatory capitalism: the case of new psychoactive substances (NPS).

    Science.gov (United States)

    Seddon, Toby

    2014-09-01

    The recent emergence of vibrant markets in 'new psychoactive substances' or 'legal highs' has posed significant new challenges for drug policy. These partly concern what to do about them but the speed and complexity of change has also raised difficulties for how policy responses should be developed. Existing drug policy systems appear too slow and cumbersome to keep up with the pace of change, remaining locked in large part within 'old' ways of thinking that centre almost exclusively around the deployment (or not) of the criminal law and its related enforcement apparatus. In this paper, it is argued that we need to rethink the problem through the lens of regulation, in order to learn lessons from other sectors where more agile responses to changing markets and business innovation have often proved possible. By examining examples drawn from these other areas, an alternative policy-making framework can be developed, involving a more flexible mix of state regulation, civil society action and private law mechanisms. This new approach is founded on a recognition of the networked and polycentric character of effective market governance in an era of global regulatory capitalism. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. [Glucokinase and glucokinase regulatory proteins as molecular targets for novel antidiabetic drugs].

    Science.gov (United States)

    Rubtsov, P M; Igudin, E L; Tiulpakov, A N

    2015-01-01

    The impairment of glucose homeostasis leads to hyperglycemia and type-2 diabetes mellitus. Glucokinase (GK), an enzyme that catalyzes the conversion of glucose to glucose-6-phosphate in pancreatic ß-cells, liver hepatocytes, specific hypothalamic neurons, and intestine enterocytes, is a key regulator of glucose homeostasis. In hepatocytes, GK controls the glucose uptake and glycogen synthesis and inhibits the glucose synthesis via the gluconeogenesis pathway. Glucokinase regulatory protein (GKRP) synthesized in hepatocytes acts as an endogenous GK inhibitor. During fasting, GKRP binds GK, inactivates it, and transports it into the cell nucleus, thus isolating it from the hepatocyte carbohydrate metabolism. In the beginning of the 2000s, the research was mainly focused on the development and trials of the small molecule GK activators as potential antidiabetic glucose-lowering drugs. However, the use of such substances increased the risk of hypoglycemia, and clinical studies of most synthetic GK activators are currently discontinued. Allosteric inhibitors of the GK-GKRP interaction are coming as alternative agents increasing the GK activity that can substitute GKA. In this review, we discuss the recent advances and the current state of art in the development of potential antidiabetic drugs targeted to GK as a key regulator of glucose homeostasis.

  17. Discrepancies in listed adverse drug reactions in pharmaceutical product information supplied by the regulatory authorities in Denmark and the USA

    DEFF Research Database (Denmark)

    Eriksson, Robert; Aagaard, Lise; Jensen, Lars Juhl

    2014-01-01

    as ADRs listed only in one country or listed with different frequencies. We analyzed PIs for 40 separate drugs from ten therapeutic groups and assigned the 4003 identified ADRs to System Organ Classes (Medical Dictionary for Regulatory Activities [MedDRA] terminology). Less than half of listed ADRs (n...

  18. Requirements for US regulatory approval of the International Thermonuclear Experimental Reactor (ITER)

    International Nuclear Information System (INIS)

    Petti, D.A.; Haire, J.C.

    1993-12-01

    The International Thermonuclear Experimental Reactor (ITER) is the first fusion machine that will have sufficient decay heat and activation product inventory to pose potential nuclear safety concerns. As a result, nuclear safety and environmental issues will be much more important in the approval process for the design, siting, construction, and operation of ITER in the United States than previous fusion devices, such as the Tokamak Fusion Test Reactor. The purpose of this report is (a) to provide an overview of the regulatory approval process for a Department of Energy (DOE) nuclear facility; (b) to present the dose limits used by DOE to protect workers, the public, and the environment from the risks of exposure to radiation and hazardous materials; (c) to discuss some key nuclear safety-related issues that must be addressed early in the Engineering Design Activities (EDA) to obtain regulatory approval; and (d) to provide general guidelines to the ITER Joint Central Team (JCT) concerning the development of a regulatory framework for the ITER project

  19. International Expert Team Concludes IAEA Peer Review of Finland's Regulatory Framework for Nuclear and Radiation Safety

    International Nuclear Information System (INIS)

    2012-01-01

    Full text: International safety experts today concluded a two-week International Atomic Energy Agency (IAEA) mission to review the regulatory framework for nuclear and radiation safety in Finland. In its preliminary report, the Integrated Regulatory Review Service (IRRS) mission team found that the Radiation and Nuclear Safety Authority of Finland (STUK) is a competent and highly credible regulator that is open and transparent and derives great strength from the technical competence of its staff. ''Finland's comprehensive regulatory framework allows STUK to operate in practice as an independent regulatory body,'' said team leader Philippe Jamet, a commissioner of the French regulatory body ASN. The mission was conducted at the request of the Government of Finland from 15-26 October. The team interviewed members of STUK and officials from various ministries, as well as key players in the Finnish safety framework. Such IRRS missions are peer reviews based on IAEA Safety Standards, not inspections or audits. The team was made up of 18 members from Bulgaria, Canada, the Czech Republic, France, Germany, Iceland, Ireland, Romania, the Russian Federation, South Africa, Slovakia, Slovenia, Spain, Sweden, the United Arab Emirates, the United Kingdom and the United States, as well as six IAEA staff members. 'The IRRS mission and preparation for it was a unique occasion that involved the whole organization, provided motivation for improvement of the safety framework in Finland and assists STUK review its mission', said Tero Varjoranta, Director General of STUK. The IRRS team identified a number of good practices and achievements, including: - STUK's excellence in its safety assessment of nuclear power plants and waste repositories, in particular its demonstration that long-term political commitment is a necessity to sustain the creation of a waste repository as well as its regulatory oversight of medical applications of radiation sources; and - STUK's excellent record in

  20. International nuclear safety experts conclude IAEA peer review of Canada's regulatory system

    International Nuclear Information System (INIS)

    2009-01-01

    Full text: An international team of nuclear safety experts today completed a two-week IAEA review of the regulatory framework and effectiveness of the Canadian Nuclear Safety Commission (CNSC). The team identified good practices within the system and gave advice on some areas for improvement. The IAEA has conveyed initial findings to Canadian authorities; the final report will be submitted by autumn. The International Atomic Energy Agency (IAEA) assembled a team of nuclear, radiation, and waste safety experts at the request of the Government of Canada, to conduct an Integrated Regulatory Review Service (IRRS) mission. The mission from 31 May to 12 June was a peer review based on IAEA Standards, not an inspection, nor an audit. The scope of the mission included sources, facilities and activities regulated by the CNSC: the operation of nuclear power plants (NPPs), research reactors and fuel cycle facilities; the refurbishment or licensing of new NPPs; uranium mining; radiation protection and environmental protection programmes; and the implementation of IAEA Code of Conduct on Safety and Security of Radioactive Sources. The 21-member team from 13 IAEA States and from the IAEA itself reviewed CNSC's work in all relevant areas: legislative and governmental responsibilities; responsibilities and functions; organization; activities of the regulatory body, including the authorization process, review and assessment, inspection and enforcement, the development of regulations, as well as guides and its the management system of CNSC. The basis for the review was a well-prepared self-assessment by the CNSC, including an evolution of its strengths and proposed actions to improve its regulatory effectiveness. Mr. Shojiro Matsuura, IRRS Team Leader and President of the Japanese Nuclear Safety Research Association, said the team 'was impressed by the extensive preparation at all CNSC staff levels.' 'We identified a number of good practices and made recommendations and suggestions

  1. The international pharmaceutical market as a source of low-cost prescription drugs for U.S. patients.

    Science.gov (United States)

    Kesselheim, Aaron S; Choudhry, Niteesh K

    2008-04-15

    In response to increasing prescription drug costs, more U.S. patients and policymakers are importing less-expensive pharmaceutical products from other countries. Large-scale prescription drug importation is currently illegal, but the U.S. Food and Drug Administration permits individuals to bring in 90-day supplies of drugs for personal use. As patient use of foreign-bought drugs has increased, federal legislators have continued to debate the full legalization of importation. Three factors help guide whether U.S. patients and policymakers can rely on other countries as sources of imported prescription drugs: whether the safety of the product can be ensured, how the import price compares with domestic prices, and how importation might affect the exporting country's pharmaceutical market. In wealthier countries with active regulatory systems, drug safety can be adequately ensured, and brand-name products are usually less expensive than in the United States (although generic drugs may be more expensive). However, implementing large-scale importation can negatively impact the originating country's market and can diminish the long-term cost savings for U.S. consumers. In low- and middle-income countries, prices may be reduced for both brand-name and generic drugs, but the prevalence of unauthorized products on the market makes ensuring drug safety more difficult. It may be reasonable for individual U.S. consumers to purchase essential medicines from certain international markets, but the most effective way to decrease drug costs overall is the appropriate use of domestic generic drugs, which are available for almost every major therapeutic class.

  2. International regulatory issues and approaches in the transition phase from operation to decommissioning

    International Nuclear Information System (INIS)

    Pyy, P.; Hrehor, M.; ); Murley, T.; Ranieri, R.; Laaksonen, J.

    2005-01-01

    Full text: The paper summarizes the work performed by an international group of senior nuclear safety regulators which was convened by the Committee on Nuclear Regulatory Activities (CNRA) of the OECD/Nuclear Energy Agency. The fundamental objective of this work was to identify the safety, environmental, organizational, human factors and public policy issues arising from decommissioning that will produce new challenges for the regulator. The study begins by recognizing that decommissioning is not simply an extension of operation and thus it is important for both the management of the facility and the regulator to understand the fundamental nature of the change taking place. Major regulatory policy issues discussed during this study include assurance of adequate funds, waste storage and disposal sites, material release criteria and site release criteria. Some of the important regulatory challenges relate to organizational and human factors, to safety and security requirements and to waste disposal and license termination. The importance of regular communication with both the corporate and site management and with public is recognized in the study as one of the key factors. When a nuclear facility ceases operation and enters into the decommissioning phase, both the operator and the regulator face a new set of challenges very different from those of an operating facility. The operator should have in place a strategic plan for decommissioning, prepared well in advance and reviewed by the regulatory body, to guide the facility managers and personnel through the changed circumstances. An essential part of the strategic plan should be the operator's plan for securing adequate funds to complete the decommissioning activities. In fact, the regulator should ensure that the operator sets aside funds, perhaps in a trust fund, while the facility is still operating and generating revenues. Both the operator and the regulator should expect a heightened public interest and concern

  3. Approaches to safety, environment and regulatory approval for the International Thermonuclear Experimental Reactor

    International Nuclear Information System (INIS)

    Saji, G.; Bartels, H.W.; Chuyanov, V.; Holland, D.; Kashirski, A.V.; Morozov, S.I.; Piet, S.J.; Poucet, A.; Raeder, J.; Rebut, P.H.; Topilski, L.N.

    1995-01-01

    International Thermonuclear Experimental Reactor (ITER) Engineering Design Activities (EDA) in safety and environment are approaching the point where conceptual safety design, topic studies and research will give way to project oriented engineering design activities. The Joint Central Team (JCT) is promoting safety design and analysis necessary for siting and regulatory approval. Scoping studies are underway at the general level, in terms of laying out the safety and environmental design framework for ITER. ITER must follow the nuclear regulations of the host country as the future construction site of ITER. That is, regulatory approval is required before construction of ITER. Thus, during the EDA, some preparations are necessary for the future application for regulatory approval. Notwithstanding the future host country's jurisdictional framework of nuclear regulations, the primary responsibility for safety and reliability of ITER rests with the legally responsible body which will operate ITER. Since scientific utilization of ITER and protection of the large investment depends on safe and reliable operation of ITER, we are highly motivated to achieve maximum levels of operability, maintainability, and safety. ITER will be the first fusion facility in which overall 'nuclear safety' provisions need to be integrated into the facility. For example, it will be the first fusion facility with significant decay heat and structural radiational damage. Since ITER is an experimental facility, it is also important that necessary experiments can be performed within some safety design limits without requiring extensive regulatory procedures. ITER will be designed with such a robust safety envelope compatible with the fusion power and the energy inventories. The basic approach to safety will be realized by 'defense-in-depth'. (orig.)

  4. International Expert Team Concludes IAEA Peer Review of Slovakia's Regulatory Framework for Nuclear Safety

    International Nuclear Information System (INIS)

    2012-01-01

    Full text: An international team of senior nuclear safety and radiation protection experts today concluded an 11-day mission to review the regulatory framework for nuclear safety in Slovakia. At the request of the Slovak Government, the IAEA assembled a team of 12 senior regulatory experts from 12 nations to conduct the Integrated Regulatory Review Service (IRRS) mission involving the Nuclear Regulatory Authority of the Slovak Republic (UJD SR). The international experts also met officials from the Public Health Authority of the Slovak Republic (UVZ SR) regarding the regulation of occupational radiation protection in nuclear facilities. The mission is a peer review based on the IAEA Safety Standards. Marta Ziakova, Chairperson of the Nuclear Regulatory Authority of Slovak Republic, declared that ''The IRRS mission has a great value for the future development and orientation of the UJD SR.'' ''Slovakia has established a regulatory framework for nuclear safety which is in line with international standards and practice,'' said Mission Team Leader Andrej Stritar, Director of the Slovenian Nuclear Safety Administration. The main observations of the IRRS Review team included: UJD SR operates with independence and transparency; UJD SR has developed and implemented a systematic training approach to meet its competence needs; and in response to the accident at TEPCO's Fukushima Daiichi Nuclear Power Station, UJD SR has reacted and communicated to interested parties, including the public. The good practices identified by the IRRS Review Team include: UJD SR has a comprehensive and well-formalized strategic approach to informing and consulting interested parties; UJD SR has developed and implemented a structured approach to training and developing its staff; and Detailed legal requirements provide a solid basis for on-site and off-site response in nuclear emergencies coordinated with local authorities. The IRRS Review team identified areas for further improvement and believes

  5. Assessment of the effectiveness of the Hungarian nuclear safety regulatory authority by international expert teams

    International Nuclear Information System (INIS)

    Voeroess, L.; Lorand, F.

    2001-01-01

    On the basis of the role nuclear regulatory authorities (NRA) have to fulfil and the new challenges affecting them, in the paper an overview is made on how the Hungarian NRA has evaluated and utilised the results of different international efforts in the enhancement of its effectiveness and efficiency. The reviews have been conducted by different groups of experts organised by highly recognised international organisations (e.g. IAEA, EC) and highly competent foreign regulatory bodies. The different reviews of activities and working conditions of the HAEA NSD have resulted in a generally positive picture, however, it also revealed weaknesses as well. They recognised the developments made in recent years and also appreciated the overall favourable level of nuclear safety in Hungary, identified 'good practices' and made recommendations and suggestions for the most important and most efficient ways for future improvements. These are cited or referenced in the paper. At the end, some recommendations have been formed based on the experiences gained from the review missions and from our self-assessment. (author)

  6. Five year results of an international proficiency testing programme for measurement of antifungal drug concentrations

    NARCIS (Netherlands)

    Lempers, V.J.C.; Alffenaar, J.W.C.; Touw, D.J.; Burger, D.M.; Uges, D.R.A.; Aarnoutse, R.E.; Brüggemann, R.J.M.

    2014-01-01

    OBJECTIVES: Since 2007 the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring (KKGT) has organized an international interlaboratory proficiency testing (PT) programme for measurement of antifungal drugs in plasma. We describe the 5 year results of the laboratories' performance.

  7. International Guidelines on Human Rights and Drug Control: A Tool for Securing Women's Rights in Drug Control Policy.

    Science.gov (United States)

    Schleifer, Rebecca; Pol, Luciana

    2017-06-01

    Discrimination and inequality shape women's experiences of drug use and in the drug trade and the impact of drug control efforts on them, with disproportionate burdens faced by poor and otherwise marginalized women. In recent years, UN member states and UN drug control and human rights entities have recognized this issue and made commitments to integrate a 'gender perspective' into drug control policies, with 'gender' limited to those conventionally deemed women. But the concept of gender in international law is broader, rooted in socially constructed and culturally determined norms and expectations around gender roles, sex, and sexuality. Also, drug control policies often fail to meaningfully address the specific needs and circumstances of women (inclusively defined), leaving them at risk of recurrent violations of their rights in the context of drugs. This article explores what it means to 'mainstream' this narrower version of gender into drug control efforts, using as examples various women's experiences as people who use drugs, in the drug trade, and in the criminal justice system. It points to international guidelines on human rights and drug control as an important tool to ensure attention to women's rights in drug control policy design and implementation.

  8. Cancer drug development and the evolving regulatory framework for companion diagnostics in the European union.

    Science.gov (United States)

    Pignatti, Francesco; Ehmann, Falk; Hemmings, Robert; Jonsson, Bertil; Nuebling, Micha; Papaluca-Amati, Marisa; Posch, Martin; Rasi, Guido

    2014-03-15

    The European Union (EU) legal framework for medical device regulation is currently under revision. The European Commission has proposed a new framework to ensure that medical devices serve the needs and ensure the safety of European citizens, aiming for a framework that is fit for purpose, more transparent, and better adapted to scientific and technological progress. The proposed new framework is described as an evolution of the current regime keeping the same legal approach. An important proposed change is that companion diagnostics will no longer be considered as low risk and subject to self-certification by the manufacturer. According to the new proposal, companion diagnostics will be classified as high individual risk or moderate public health risk (category C) and require conformity assessment by a notified body. It has also been proposed that evidence of the clinical utility of the device for the intended purpose should be required for companion diagnostics. In this article, we review the EU legal framework relevant for companion diagnostics, describe the proposed changes, and summarize the available scientific guidance from the European Medicines Agency and its regulatory experience with cancer drug development including companion diagnostics. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." ©2014 AACR.

  9. Standardisation of defined approaches for skin sensitisation testing to support regulatory use and international adoption: position of the International Cooperation on Alternative Test Methods.

    Science.gov (United States)

    Casati, S; Aschberger, K; Barroso, J; Casey, W; Delgado, I; Kim, T S; Kleinstreuer, N; Kojima, H; Lee, J K; Lowit, A; Park, H K; Régimbald-Krnel, M J; Strickland, J; Whelan, M; Yang, Y; Zuang, Valérie

    2018-02-01

    Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of the skin sensitisation adverse outcome pathway. Nevertheless, the currently adopted methods, when used in isolation, are not sufficient to fulfil regulatory requirements on the skin sensitisation potential and potency of chemicals comparable to that provided by the regulatory animal tests. For this reason, a number of defined approaches integrating data from these methods with other relevant information have been proposed and documented by the OECD. With the aim to further enhance regulatory consideration and adoption of defined approaches, the European Union Reference Laboratory for Alternatives to Animal testing in collaboration with the International Cooperation on Alternative Test Methods hosted, on 4-5 October 2016, a workshop on the international regulatory applicability and acceptance of alternative non-animal approaches, i.e., defined approaches, to skin sensitisation assessment of chemicals used in a variety of sectors. The workshop convened representatives from more than 20 regulatory authorities from the European Union, United States, Canada, Japan, South Korea, Brazil and China. There was a general consensus among the workshop participants that to maximise global regulatory acceptance of data generated with defined approaches, international harmonisation and standardisation are needed. Potential assessment criteria were defined for a systematic evaluation of existing defined approaches that would facilitate their translation into international standards, e.g., into a performance-based Test Guideline. Informed by the discussions at the workshop, the ICATM members propose practical ways to further promote the regulatory use and facilitate

  10. National Institute on Drug Abuse International Program: improving opioid use disorder treatment through international research training.

    Science.gov (United States)

    Gust, Steven W; McCormally, Judy

    2018-07-01

    For more than 25 years, the National Institute on Drug Abuse (NIDA) has supported research-training programs, establishing a global research network and expanding the knowledge base on substance use disorders. International research to inform approaches to opioid addiction is particularly important and relevant to the United States, where opioid misuse, addiction, and overdose constitute an emerging public health crisis. This article summarizes the NIDA International Program and illustrates its impact by reviewing recent articles about treatment approaches for opioid use disorders (OUD). Studies in several countries have demonstrated the effectiveness of physician office-based opioid substitution therapies. Other research has demonstrated the effectiveness of different formulations and doses of the opioid antagonist naltrexone, as well as different approaches to providing naloxone to treat opioid overdose. Continuing research into implementation of evidence-based treatment in international settings with limited resources is applicable to US regions that face similar structural, legal, and fiscal constraints. The current review describes international research on OUD treatment and opioid overdose, most coauthored by former NIDA fellows. The findings from outside the United States have important implications for best practices domestically and in other countries that are experiencing increases in OUD prevalence and related overdose deaths.

  11. Ethical and Regulatory Challenges with Autologous Adult Stem Cells: A Comparative Review of International Regulations.

    Science.gov (United States)

    Lysaght, Tamra; Kerridge, Ian H; Sipp, Douglas; Porter, Gerard; Capps, Benjamin J

    2017-06-01

    Cell and tissue-based products, such as autologous adult stem cells, are being prescribed by physicians across the world for diseases and illnesses that they have neither been approved for or been demonstrated as safe and effective in formal clinical trials. These doctors often form part of informal transnational networks that exploit differences and similarities in the regulatory systems across geographical contexts. In this paper, we examine the regulatory infrastructure of five geographically diverse but socio-economically comparable countries with the aim of identifying similarities and differences in how these products are regulated and governed within clinical contexts. We find that while there are many subtle technical differences in how these regulations are implemented, they are sufficiently similar that it is difficult to explain why these practices appear more prevalent in some countries and not in others. We conclude with suggestions for how international governance frameworks might be improved to discourage the exploitation of vulnerable patient populations while enabling innovation in the clinical application of cellular therapies.

  12. Participation of the Nuclear Regulatory Authority in the 'Third European Intercomparison Exercise on Internal Dose Assessment'

    International Nuclear Information System (INIS)

    Rojo, Ana Maria; Gomez Parada, Ines Maria

    2001-01-01

    This paper resume the participation of the Argentine Nuclear Regulatory Authority (ARN) in the 'Third European Intercomparison Exercise on Internal Dose Assessment'. It takes place during 5 months in 1998 and the final meeting was held in Weimar, Germany, on May 1999. This exercise involved the previous distribution of seven cases, simulated and real, describing possible incorporations of radioactive materials. There was a description of the event, data of retention or excretion measurements and air concentration data. The fifty participants belong to twenty three countries had do solve the cases and informed the results to the organizers, mainly the incorporation and effective dose was required. The objective was to review the methodology, the codes and the different assumptions used by the participants for discussing the consistent of the result. The results are shown through tables including the maximum and minimum values gave for the final report and the results informed by ARN. This exercise allowed to compare the methodology used by the ARN internal dosimetry group with other choose by several international groups to assure that the codes, assumptions and methodology were satisfactory to solve the different cases given by the organizers. (author)

  13. International regulatory landscape and integration of corrective genome editing into in vitro fertilization.

    Science.gov (United States)

    Araki, Motoko; Ishii, Tetsuya

    2014-11-24

    Genome editing technology, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas, has enabled far more efficient genetic engineering even in non-human primates. This biotechnology is more likely to develop into medicine for preventing a genetic disease if corrective genome editing is integrated into assisted reproductive technology, represented by in vitro fertilization. Although rapid advances in genome editing are expected to make germline gene correction feasible in a clinical setting, there are many issues that still need to be addressed before this could occur. We herein examine current status of genome editing in mammalian embryonic stem cells and zygotes and discuss potential issues in the international regulatory landscape regarding human germline gene modification. Moreover, we address some ethical and social issues that would be raised when each country considers whether genome editing-mediated germline gene correction for preventive medicine should be permitted.

  14. Influence of Japanese Regulatory Action on Denosumab-Related Hypocalcemia Using Japanese Adverse Drug Event Report Database.

    Science.gov (United States)

    Takeyama, Mayu; Sai, Kimie; Imatoh, Takuya; Segawa, Katsunori; Hirasawa, Noriyasu; Saito, Yoshiro

    2017-01-01

    The anti-receptor activator of nuclear factor kappa-B ligand (RANKL) antibody, Denosumab (DEN), was approved in April 2012 in Japan, but a Dear Healthcare Professional Letter of Rapid Safety Communication was released in September, 2012 by the regulatory authority because of the severe hypocalcemia risks. Currently, the effectiveness of this regulatory action has not been evaluated and, therefore, this study aimed to assess its impact on DEN-induced hypocalcemia using the Japanese Adverse Drug Event Report database (JADER). The case reports from April 2012 to September 2014 were collected from the JADER, which included 151642 adverse events for the primary suspected drugs. The reporting odds ratio (ROR) of hypocalcemia as a signal of the target adverse event was analyzed for DEN and zoledronic acid (ZOL, a reference drug). Changes in RORs were compared between the pre- (Pre, April 2012 to September 2012) and post- (Post 1, October 2012 to September 2013 and Post 2, October 2013 to September 2014) periods of the regulatory action. A decrease in the hypocalcemia ROR was observed for DEN in the post-periods, especially Post 2. Multivariate logistic regression analysis showed a significant decrease in hypocalcemia signal in Post 1 (p=0.0306 vs. Pre) and Post 2 (p=0.0054 vs. Pre). ZOL caused no significant changes in ROR of hypocalcemia, and none of the drugs caused ROR changes in jaw osteonecrosis (a reference adverse event). This study suggests that the regulatory action against hypocalcemia in DEN effectively decreased hypocalcemia signal. Further studies using medical information databases are needed to confirm this result.

  15. Discrepancies in listed adverse drug reactions in pharmaceutical product information supplied by the regulatory authorities in Denmark and the USA.

    Science.gov (United States)

    Eriksson, Robert; Aagaard, Lise; Jensen, Lars Juhl; Borisova, Liza; Hørlück, Dorte; Brunak, Søren; Hansen, Ebba Holme

    2014-06-01

    Pharmaceutical product information (PI) supplied by the regulatory authorities serves as a source of information on safe and effective use of drugs. The objectives of this study were to qualitatively and quantitatively compare PIs for selected drugs marketed in both Denmark and the USA with respect to consistency and discrepancy of listed adverse drug reaction (ADR) information. We compared individual ADRs listed in PIs from Denmark and the USA with respect to type and frequency. Consistency was defined as match of ADRs and of ADR frequency or match could not be ruled out. Discrepancies were defined as ADRs listed only in one country or listed with different frequencies. We analyzed PIs for 40 separate drugs from ten therapeutic groups and assigned the 4003 identified ADRs to System Organ Classes (Medical Dictionary for Regulatory Activities [MedDRA] terminology). Less than half of listed ADRs (n = 1874; 47%) showed consistency. Discrepancies (n = 2129; 53%) were split into ADRs listed only in the USA (n = 1558; 39%), ADRs listed only in Denmark (n = 325; 8%) and ADRs listed with different frequencies (n = 246; 6%). The majority of listed ADRs were of the type "gastrointestinal disorders" and "nervous system disorders". Our results show great differences in PIs for drugs approved in both Denmark and the USA illuminating concerns about the credibility of the publicly available PIs. The results also represent an argument for further harmonization across borders to improve consistency between authority-supplied information.

  16. Advancing regulatory science to bring novel medical devices for use in emergency care to market: the role of the Food and Drug Administration.

    Science.gov (United States)

    Scully, Christopher G; Forrest, Shawn; Galeotti, Loriano; Schwartz, Suzanne B; Strauss, David G

    2015-04-01

    The Food and Drug Administration (FDA) performs regulatory science to provide science-based medical product regulatory decisions. This article describes the types of scientific research the FDA's Center for Devices and Radiological Health performs and highlights specific projects related to medical devices for emergency medicine. In addition, this article discusses how results from regulatory science are used by the FDA to support the regulatory process as well as how the results are communicated to the public. Regulatory science supports the FDA's mission to assure safe, effective, and high-quality medical products are available to patients. Published by Elsevier Inc.

  17. Information to Improve Public Perceptions of the Food and Drug Administration (FDA’s Tobacco Regulatory Role

    Directory of Open Access Journals (Sweden)

    Amira Osman

    2018-04-01

    Full Text Available While the Food and Drug Administration (FDA has had regulatory authority over tobacco products since 2009, public awareness of this authority remains limited. This research examines several broad types of information about FDA tobacco regulatory mission that may improve the perceptions of FDA as a tobacco regulator. Using Amazon Mechanical Turk, 1766 adults, smokers and non-smokers, were randomly assigned to view a statement about FDA regulatory authority that varied three information types in a 2 × 2 × 2 between subjects experimental design: (1 FDA’s roles in regulating tobacco (yes/no; (2 The scientific basis of regulations (yes/no; and (3 A potential protective function of regulations (yes/no. Using factorial ANOVA, we estimated the main and interactive effects of all three types of information and of smoking status on the perceptions of FDA. Participants that were exposed to information on FDA roles reported higher FDA credibility and a greater perceived knowledge of FDA than those who did not. Exposure to information about the scientific basis of regulations led to more negative views of the tobacco industry. Participants who learned of the FDA’s commitment to protecting the public reported higher FDA credibility and more positive attitudes toward regulations than those who did not learn of this commitment. We observed no significant interaction effects. The findings suggest that providing information about the regulatory roles and protective characterization of the FDA’s tobacco regulatory mission positively influence public perceptions of FDA and tobacco regulations.

  18. [International cooperation in combatting illicit drugs in Mozambique].

    Science.gov (United States)

    Buvana, Flávia; Ventura, Carla Aparecida Arena

    2011-06-01

    Countries from Southern Africa have formed a Development Community (SADC) to stimulate common actions in several areas, among them illicit drugs combat. In this context, the goal of this qualitative study was to identify information and perception about the cooperation set up between Mozambique and other SADC members in combatting illicit drugs. Data were collected through semi-structured interviews with public employees developing actions directed at the implementation of the Protocol to Combat Drugs in SADC. After transcriptions, the interviews were analyzed by content analysis and resulted in the categories: "Mozambique as a drugs corridor", "Cooperation Initiatives on Drugs among African countries", "Cooperation Difficulties in Africa", "Problems in Protocol Implementation" and "Difficulties to implement a control policy". As a consequence, there is a need to review and update the policies and strategies in the drugs area, as they are not contextualized in the country's current reality.

  19. Control authorities of internal affairs bodies in the sphere of drug trafficking

    Directory of Open Access Journals (Sweden)

    О. М. Шевчук

    2014-06-01

    Full Text Available The article deals with control authorities of internal Affairs bodies in the sphere of turnover of narcotic drugs, psychotropic substances and precursors. Established the concept of the legal status of the Management of the fight against illegal circulation of drugs of the Ministry of interior of Ukraine and describes its features. The classification of control authorities of internal Affairs bodies in the sphere of turnover of narcotic drugs, psychotropic substances and precursors and analyzed for their content.

  20. Priority setting for orphan drugs: an international comparison.

    Science.gov (United States)

    Rosenberg-Yunger, Zahava R S; Daar, Abdallah S; Thorsteinsdóttir, Halla; Martin, Douglas K

    2011-04-01

    To describe the process of priority setting for two orphan drugs - Cerezyme and Fabrazyme - in Canada, Australia and Israel, in order to understand and improve the process based on stakeholder perspectives. We conducted qualitative case studies of how three independent drug advisory committees made decisions relating to the funding of Cerezyme and Fabrazyme. Interviews were conducted with 22 informants, including committee members, patient groups and industry representatives. (1) DESCRIPTION: Orphan drugs reimbursement recommendations by expert panels were based on clinical evidence, cost and cost-effectiveness analysis. (2) EVALUATION: Committee members expressed an overall preference for the current drug review process used by their own committee, but were concerned with the fairness of the process particularly for orphan drugs. Other informants suggested the inclusion of other relevant values (e.g. lack of alternative treatments) in order to improve the priority setting process. Some patient groups suggested the use of an alternative funding mechanism for orphan drugs. Priority setting for drugs is not solely a technical process (involving cost-effective analysis, evidence-based medicine, etc.). Understanding the process by which reimbursement decisions are made for orphan drugs may help improve the system for future orphan drugs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  1. 76 FR 47630 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2011-08-05

    ... data and other products available to persons that are not members of the self-regulatory organization... in self-regulatory organization governance was mandated by the Act, non-members should be given the... the evolution of self-regulatory organization governance and competitive market structure have...

  2. 75 FR 61795 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2010-10-06

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63017; File No. SR-ISE-2010-95] Self-Regulatory...\\ 15 U.S.C. 78s(b)(3)(A). \\4\\ 17 CFR 240.19b-4(f)(6). I. Self-Regulatory Organization's Statement of... Exchange, and at the Commission's Public Reference Room. II. Self-Regulatory Organization's Statement of...

  3. 76 FR 77275 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

    Science.gov (United States)

    2011-12-12

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65900; File No. SR-ISE-2011-82] Self-Regulatory... text of these statements may be examined at the places specified in Item IV below. The self-regulatory... such statements. A. Self-Regulatory Organization's Statement of the Purpose of, and Statutory Basis for...

  4. THE MEDICO-SCIENTIFIC MARGINALISATION OF HOMEOPATHY: INTERNATIONAL LEGAL AND REGULATORY DEVELOPMENTS.

    Science.gov (United States)

    Freckelton, Ian

    2015-09-01

    The 2010 report of the United Kingdom Science and Technology Committee of the House of Commons and the 2015 report of the Australian National Health and Medical Research Council have overtaken in significance the uncritical Swiss report of 2012 and have gone a long way to changing the environment of tolerance toward proselytising claims of efficacy in respect of homeopathy. The inquiry being undertaken in the United States by the Food and Drug Administration during 2015 may accelerate this trend. An outcome of the reports and inquiries has been a series of decisions from advertising regulators and by courts rejecting medically unjustifiable claims in respect of the efficacy of homeopathy. Class actions have also been initiated in North America against manufacturers of homeopathic products. The changing legal and regulatory environment is generating an increasingly scientifically marginalised existence for homeopathy. That new environment is starting to provide effective inhibition of assertions on behalf of homeopathy and other health modalities whose claims to therapeutic efficacy cannot be justified by reference to the principles of evidence-based health care. This has the potential to reduce the financial support that is provided by insurers and governments toward homeopathy and to result in serious liability exposure for practitioners, manufacturers and those who purvey homeopathic products, potentially including pharmacists. In addition, it may give a fillip to a form of regulation of homeopaths if law reform to regulate unregistered health practitioners gathers momentum, as is taking place in Australia.

  5. International Drug Discovery Science and Technology--BIT's Seventh Annual Congress.

    Science.gov (United States)

    Bodovitz, Steven

    2010-01-01

    BIT's Seventh Annual International Drug Discovery Science and Technology Congress, held in Shanghai, included topics covering new therapeutic and technological developments in the field of drug discovery. This conference report highlights selected presentations on open-access approaches to R&D, novel and multifactorial targets, and technologies that assist drug discovery. Investigational drugs discussed include the anticancer agents astuprotimut-r (GlaxoSmithKline plc) and AS-1411 (Antisoma plc).

  6. Drug user organizations in the Nordic countries--local, national, and international dimensions.

    Science.gov (United States)

    Frank, Vibeke Asmussen; Anker, Jørgen; Tammi, Tuukka

    2012-04-01

    The article focuses on drug user organizations that represent and advocate for active "hard drug" users in the Nordic countries. It discusses the opportunities and challenges that these organizations face in their search for legitimacy and political influence. The comparative perspective points at similarities and differences in national contexts that both support and challenges the existence of drug user organizations, including drug policy, social welfare policy, trends in drug use, and organizational conditions. The article also discusses the importance of international network and transnational organizations that support drug user organizations.

  7. A qualitative examination of the effects of international counter-drug interdictions.

    Science.gov (United States)

    Toth, Alexander G; Mitchell, Ojmarrh

    2018-05-01

    The purpose of this study is to utilize unique qualitative data to determine the effects of sporadic international drug interdictions on drug trafficking, and to assess whether the responses of drug traffickers align with rational choice theory. Qualitative data obtained from 23 high-level United States Drug Enforcement Administration (DEA) informants, who are embedded in international drug trafficking groups, are examined to identify common responses to drug interdiction operations. The findings indicate that sporadic counter-drug interdictions do not a have permanent deterrent effect on transnational drug smuggling operations. However, these types of law enforcement operations produce temporary alterations in drug trafficking, as traffickers adopted a variety of methods to thwart the efforts of law enforcement-often by relying on information acquired from corrupt local law enforcement. The results also indicate that while interdiction operations displaced trafficking activities (temporally, spatially, and methodological), there is little evidence that drug traffickers responded to such operations by moving into new areas (i.e., malign spatial displacement). Sporadic international drug interdiction programs do little to deter drug trafficking organizations (DTOs) from engaging in their illicit trade. Instead, DTOs adjust in a calculating manner to these operations to ensure that their illegal products reach consumer marketplaces, which is congruent with the rational choice theoretical perspective. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Regulatory activities

    International Nuclear Information System (INIS)

    2001-01-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

  9. 78 FR 27113 - Generic Drug User Fee Amendments of 2012; Regulatory Science Initiatives Public Hearing; Request...

    Science.gov (United States)

    2013-05-09

    ... Hearing; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public hearing; request for public comments. The Food and Drug Administration (FDA or the Agency) is announcing a... of complex drug substances 13. Develop a risk-based understanding of potential adverse impacts to...

  10. [European Union regulatory and quality requirements for botanical drugs and their implications for Chinese herbal medicinal products development].

    Science.gov (United States)

    Zhu, You-Ping

    2017-06-01

    This paper introduces regulatory pathways and characteristic quality requirements for marketing authorization of herbal medicinal products in the European Union(EU), and the legal status and applications of "European Union list of herbal substances, preparations and combinations" and "European Union herbal monographs". Also introduced are Chinese herbs that have been granted the EU list entry, those with EU herbal monographs, and registered EU traditional herbal medicinal products with Chinese herbs as active ingredients. Special attention is paid to the technical details of three authorized EU herbal medicinal products (Veregen, Sativex and Episalvan) in comparison with Andrographis paniculata extract HMPL-004 that failed the phase Ⅲ clinical trial for ulcerative colitis. The paper further emphasizes the importance of enriching active fractions of herbal extracts and taking regulatory and quality considerations into account in early stage of botanical drug development. Copyright© by the Chinese Pharmaceutical Association.

  11. Policy, regulatory and international spects of the disposal of low - and intermediate radioactive waste and other hazardous waste

    International Nuclear Information System (INIS)

    Olivier, J.P.

    1989-01-01

    This paper focuses on the management of low- and intermediate-level radioactive waste. It recalls briefly the technical background and the main features of the regulatory systems adopted by most countries for their radioactive wastes, the respective role of technical and institutional measures contributing to safety, and the influence of international cooperation. A very preliminary attempt is made to draw a parallel with the situation existing for other hazardous wastes, underlying in particular those aspects which seem important in the discussion of management and regulatory policies

  12. 76 FR 39143 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2011-07-05

    ... possibility for disruption of the options market itself, especially in illiquid options classes. See... illegal trading activity. In addition, routine oversight inspections of the Exchange's regulatory programs...

  13. DREISS: Using State-Space Models to Infer the Dynamics of Gene Expression Driven by External and Internal Regulatory Networks

    Science.gov (United States)

    Gerstein, Mark

    2016-01-01

    Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem’s gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally–e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution. We developed a computational method (DREISS, dreiss.gerteinlab.org) for analyzing the Dynamics of gene expression driven by Regulatory networks, both External and Internal based on State Space models. Given a subsystem, the “state” and “control” in the model refer to its own (internal) and another subsystem’s (external) gene expression levels. The state at a given time is determined by the state and control at a previous time. Because typical time-series data do not have enough samples to fully estimate the model’s parameters, DREISS uses dimensionality reduction, and identifies canonical temporal expression trajectories (e.g., degradation, growth and oscillation) representing the regulatory effects emanating from various subsystems. To demonstrate capabilities of DREISS, we study the regulatory effects of evolutionarily conserved vs. divergent TFs across distant species. In particular, we applied DREISS to the time-series gene expression datasets of C. elegans and D. melanogaster during their embryonic development. We analyzed the expression dynamics of the conserved, orthologous genes (orthologs), seeing the degree to which these can be accounted for by orthologous (internal) versus species-specific (external) TFs. We found that between two species, the orthologs have matched, internally driven expression patterns but very different externally driven ones. This is particularly true for genes with

  14. DREISS: Using State-Space Models to Infer the Dynamics of Gene Expression Driven by External and Internal Regulatory Networks.

    Directory of Open Access Journals (Sweden)

    Daifeng Wang

    2016-10-01

    Full Text Available Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs, cellular growth factors and microRNAs. A subsystem's gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally-e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution. We developed a computational method (DREISS, dreiss.gerteinlab.org for analyzing the Dynamics of gene expression driven by Regulatory networks, both External and Internal based on State Space models. Given a subsystem, the "state" and "control" in the model refer to its own (internal and another subsystem's (external gene expression levels. The state at a given time is determined by the state and control at a previous time. Because typical time-series data do not have enough samples to fully estimate the model's parameters, DREISS uses dimensionality reduction, and identifies canonical temporal expression trajectories (e.g., degradation, growth and oscillation representing the regulatory effects emanating from various subsystems. To demonstrate capabilities of DREISS, we study the regulatory effects of evolutionarily conserved vs. divergent TFs across distant species. In particular, we applied DREISS to the time-series gene expression datasets of C. elegans and D. melanogaster during their embryonic development. We analyzed the expression dynamics of the conserved, orthologous genes (orthologs, seeing the degree to which these can be accounted for by orthologous (internal versus species-specific (external TFs. We found that between two species, the orthologs have matched, internally driven expression patterns but very different externally driven ones. This is particularly true for genes with

  15. International trends in alcohol and drug use among vehicle drivers.

    Science.gov (United States)

    Christophersen, A S; Mørland, J; Stewart, K; Gjerde, H

    2016-01-01

    Trends in the use of alcohol and drugs among motor vehicle drivers in Australia, Brazil, Norway, Spain, and the United States have been reviewed. Laws, regulations, enforcement, and studies on alcohol and drugs in biological samples from motor vehicle drivers in general road traffic and fatal road traffic crashes (RTCs) are discussed. Roadside surveys showed a reduction of drunk driving over time in the studied countries; however, the pattern varied within and between different countries. The reduction of alcohol use may be related to changes in road traffic laws, public information campaigns, and enforcement, including implementation of random breath testing or sobriety checkpoints. For non-alcohol drugs, the trend in general road traffic is an increase in use. However, drugs were not included in older studies; it is therefore impossible to assess the trends over longer time periods. Data from the studied countries, except Brazil, have shown a significant decrease in fatal RTCs per 100,000 inhabitants over the last decades; from 18.6 to 4.9 in Australia, 14.5 to 2.9 in Norway, 11.1 to 3.6 in Spain, and 19.3 to 10.3 in the United States. The number of alcohol-related fatal RTCs also decreased during the same time period. The proportion of fatal RTCs related to non-alcohol drugs increased, particularly for cannabis and stimulants. A general challenge when comparing alcohol and drug findings in biological samples from several countries is connected to differences in study design, particularly the time period for performing roadside surveys, biological matrix types, drugs included in the analytical program, and the cutoff limits used for evaluation of results. For RTC fatalities, the cases included are based on the police requests for legal autopsy or drug testing, which may introduce a significant selection bias. General comparisons between high-income countries and low- and middle-income countries as well as a discussion of possible future trends are included

  16. Regulation of drug metabolism and toxicity by multiple factors of genetics, epigenetics, lncRNAs, gut microbiota, and diseases: a meeting report of the 21st International Symposium on Microsomes and Drug Oxidations (MDO

    Directory of Open Access Journals (Sweden)

    Ai-Ming Yu

    2017-03-01

    Full Text Available Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21st International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2–6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.

  17. 78 FR 47457 - Self-Regulatory Organizations: Miami International Securities Exchange LLC; Notice of Filing and...

    Science.gov (United States)

    2013-08-05

    ... innovative pricing strategy. The Exchange notes that if the extension of the fee waiver results in a modest... to Market Makers including marketing fees, Options Regulatory Fees, market data, and membership... may apply to Market Makers including marketing fees, Options Regulatory Fees, market data, and...

  18. 78 FR 35349 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and...

    Science.gov (United States)

    2013-06-12

    ... by adopting an innovative pricing strategy. The Exchange notes that if the fee waiver resulted in a... apply to Market Makers including marketing fees, Options Regulatory Fees, market data, and membership... Market Makers including marketing fees, Options Regulatory Fees, market data, and membership application...

  19. 78 FR 26375 - Food and Drug Administration/International Society for Pharmaceutical Engineering Co-Sponsorship...

    Science.gov (United States)

    2013-05-06

    ...] Food and Drug Administration/International Society for Pharmaceutical Engineering Co-Sponsorship... Society of Pharmaceutical Engineering (ISPE), is announcing a conference entitled ``Redefining the `C' in CGMP: Creating, Implementing and Sustaining a Culture of Quality'' Pharmaceutical Quality System (ICH...

  20. Independence in regulatory decision making - INSAG-17. A report by the International Nuclear Safety Advisory Group

    International Nuclear Information System (INIS)

    2003-01-01

    This report is intended to promote a common understanding among legislators and other political decision makers, nuclear safety regulators and licensees of the concept of independence in regulatory decision making and how to achieve it. Other interest groups, such as non-governmental organizations and members of the public interested in the regulation of nuclear safety, may also find the report useful. The principles concerning the independence of regulatory organizations are developed and discussed in publications in the IAEA's Safety Standards Series. Although the principles relating to protecting the independence of the regulatory body provide the necessary basis for independence in regulatory decision making, there are additional factors and features that require attention to ensure independence in the decision making by the regulatory body. This INSAG report highlights and discusses a number of such factors and features

  1. Modeling attitude towards drug treament: the role of internal motivation, external pressure, and dramatic relief.

    Science.gov (United States)

    Conner, Bradley T; Longshore, Douglas; Anglin, M Douglas

    2009-04-01

    Motivation for change has historically been viewed as the crucial element affecting responsiveness to drug treatment. Various external pressures, such as legal coercion, may engender motivation in an individual previously resistant to change. Dramatic relief may be the change process that is most salient as individuals internalize such external pressures. Results of structural equation modeling on data from 465 drug users (58.9% male; 21.3% Black, 34.2% Hispanic/Latino, and 35.1% White) entering drug treatment indicated that internal motivation and external pressure significantly and positively predicted dramatic relief and that dramatic relief significantly predicted attitudes towards drug treatment: chi (2) = 142.20, df = 100, p relief is also likely to be high. When dramatic relief is high, attitudes towards drug treatment are likely to be positive. The findings indicate that interventions to get individuals into drug treatment should include processes that promote Dramatic Relief. Implications for addictions health services are discussed.

  2. Regulatory inspection activities related to inspection planning, plant maintenance and assessment of safety. Proceedings of an international workshop

    Energy Technology Data Exchange (ETDEWEB)

    Van Binnebeek, J. J. [AIB-Vincotte Nuclear - AVN, Avenue du Roi, 157, B-1060 Brussels (Belgium); Aubrey, Richard; Grandame, Melvyn [Atomic Energy Control Board - AECB, P.O. Box 1046, Station B, 280 Slater Street, Ottawa, Ontario K1P 5S9 (Canada); Aro, Ilari [Finnish Centre for Radiation and Nuclear Safety - STUK, P.O. Box 14, FIN-00881 Helsinki (Finland); Balloffet, Yves [DRIRE Rhone Alpes, 146, rue Pierre Corneille, 69426 Lyon CEDEX 03 (France); Klonk, Hartmut [Bundesamt fuer Strahlenschutz - BfS, Federal Office for Radiation Protection, Postbox 10 01 49, 38201 Salzgitter 1 (Germany); Manzella, Pietro [A.N.P.A., Via V. Brancati, 48, 1-00144 Roma EUR (Italy); Koizumi, Hiroyoshi [Tech. Stan. Dept. - JAPEIC, Shin-Toranomon Bldg., 1-5-11, Akasaka, Minato-ku, Tokyo 107 (Japan); Bouvrie, E.C. des [Ministry of Social Affairs and Employment, Nuclear Safety Dept. KFD, P.O. Box 90804, 2509 LV The Hague (Netherlands); Forsberg, Staffan [Swedish Nuclear Power Inspectorate - SKI, Klarabergsviadukten 90, S-10658 Stockholm (Sweden); Lang, Hans-Guenter [Section Plant Coordination and Inspection, Swiss Federal Nuclear Safety Inspectorate - HSK, CH-5232 Villigen-HSK (Switzerland); Mehew, Robert; Warren, Thomas; Woodhouse, Paul [Health and Safety Executive - NII, St. Peter' s House, Balliol Road, Bootle, Merseyside L20 3LZ (United Kingdom); Gallo, Robert M. [Special Inspection Branch, US Nuclear Regulatory Commission - US NRC, Mail Stop 0-9A1, Washington, DC 20555 (United States); Campbell, Rob [International Atomic Energy Agency - IAEA, P.O. Box 100, A-1400 Vienna (International Atomic Energy Agency (IAEA))

    1997-07-01

    The NEA Committee on Nuclear Regulatory Activities (CNRA) believes that an essential factor in ensuring the safety of nuclear installations is the continuing exchange and analysis of technical information and data. To facilitate this exchange the Committee has established Working Groups and Groups of Experts in specialised topics. CNRA believes that safety inspections are a major element in the regulatory authority's efforts to ensure the safe operation of nuclear facilities. Considering the importance of these issues, the Committee has established a special Working Group on Inspection Practices (WGIP). The purpose of WGIP, is to facilitate the exchange of information and experience related to regulatory safety inspections between CNRA Member countries. This was the 3. international workshop held by the WGIP on regulatory inspection activities. The focus of this workshop was on 3 main topics; Inspection Planning, Plant Maintenance and Assessment of Safety. This document presents the proceedings from the workshop, including: workshop programme, results and conclusions, papers and presentations and the list of participants. The main purpose of the Workshop is to provide a forum of exchange of information on the regulatory inspection activities.

  3. Regulatory inspection activities related to inspection planning, plant maintenance and assessment of safety. Proceedings of an international workshop

    International Nuclear Information System (INIS)

    Van Binnebeek, J.J.; Aubrey, Richard; Grandame, Melvyn; Aro, Ilari; Balloffet, Yves; Klonk, Hartmut; Manzella, Pietro; Koizumi, Hiroyoshi; Bouvrie, E.C. des; Forsberg, Staffan; Lang, Hans-Guenter; Mehew, Robert; Warren, Thomas; Woodhouse, Paul; Gallo, Robert M.; Campbell, Rob; )

    1997-01-01

    The NEA Committee on Nuclear Regulatory Activities (CNRA) believes that an essential factor in ensuring the safety of nuclear installations is the continuing exchange and analysis of technical information and data. To facilitate this exchange the Committee has established Working Groups and Groups of Experts in specialised topics. CNRA believes that safety inspections are a major element in the regulatory authority's efforts to ensure the safe operation of nuclear facilities. Considering the importance of these issues, the Committee has established a special Working Group on Inspection Practices (WGIP). The purpose of WGIP, is to facilitate the exchange of information and experience related to regulatory safety inspections between CNRA Member countries. This was the 3. international workshop held by the WGIP on regulatory inspection activities. The focus of this workshop was on 3 main topics; Inspection Planning, Plant Maintenance and Assessment of Safety. This document presents the proceedings from the workshop, including: workshop programme, results and conclusions, papers and presentations and the list of participants. The main purpose of the Workshop is to provide a forum of exchange of information on the regulatory inspection activities

  4. Secondary harm mitigation: A more humanitarian framework for international drug law enforcement.

    Science.gov (United States)

    Blaustein, Jarrett; McLay, Miki; McCulloch, Jude

    2017-08-01

    This article introduces the concept of 'secondary harm mitigation' as a framework for improving the humanitarian credentials of international drug law enforcement agencies. The concept is rooted in a critical analysis of the compatibility of the harm reduction philosophy with Australia's international drug law enforcement practices. On a utilitarian level, the net benefits of international drug law enforcement are determined to be, at best inconclusive, arguably counterproductive and in most cases, incalculable. On a humanitarian level, international drug law enforcement is also determined to be problematic from a criminological standpoint because it generates secondary harms and it is indifferent to the vulnerability of individuals who participate in illicit drug trafficking. Accordingly, the article concludes that a philosophy of harm reduction grounded in the public health perspective is inadequate for mitigating secondary harms arising from Australia's efforts to combat international illicit drug trafficking. A tentative list of secondary harm mitigation principles is presented and the article argues that secondary harm mitigation should replace supply reduction as a core tenet of Australia's National Drug Strategy. The article also concludes that secondary harm mitigation may provide a viable framework for stimulating a productive dialogue between those who advocate prohibition and those who call for decriminalisation at the global level. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Rational drug use--evaluation of a training programme for interns.

    Science.gov (United States)

    Natu, M V; Zachariah, P; Zachariah, A; Chand, S; Singh, T; Choudhry, K

    1995-09-01

    A workshop covering various aspects of rational drug use was conducted for interns of Christian Medical College, Ludhiana. Evaluation of the workshop revealed that it was able to bring about an attitudinal change regarding rational drug use. The methodology and evaluation procedures have been described. It is suggested that similar attempts should be made at all medical colleges so that every graduate enters medical practice with a positive attitude towards rational drug use.

  6. 77 FR 69634 - International Conference on Harmonisation; Guidance on Q11 Development and Manufacture of Drug...

    Science.gov (United States)

    2012-11-20

    ...] International Conference on Harmonisation; Guidance on Q11 Development and Manufacture of Drug Substances... Administration (FDA) is announcing the availability of a guidance entitled ``Q11 Development and Manufacture of... guidance is intended to apply only to the manufacture of drug substance, not the manufacture of finished...

  7. Internalized HIV and Drug Stigmas: Interacting Forces Threatening Health Status and Health Service Utilization Among People with HIV Who Inject Drugs in St. Petersburg, Russia

    Science.gov (United States)

    Burke, Sara E.; Dovidio, John F.; Levina, Olga S.; Uusküla, Anneli; Niccolai, Linda M.; Heimer, Robert

    2016-01-01

    Marked overlap between the HIV and injection drug use epidemics in St. Petersburg, Russia, puts many people in need of health services at risk for stigmatization based on both characteristics simultaneously. The current study examined the independent and interactive effects of internalized HIV and drug stigmas on health status and health service utilization among 383 people with HIV who inject drugs in St. Petersburg. Participants self-reported internalized HIV stigma, internalized drug stigma, health status (subjective rating and symptom count), health service utilization (HIV care and drug treatment), sociodemographic characteristics, and health/behavioral history. For both forms of internalized stigma, greater stigma was correlated with poorer health and lower likelihood of service utilization. HIV and drug stigmas interacted to predict symptom count, HIV care, and drug treatment such that individuals internalizing high levels of both stigmas were at elevated risk for experiencing poor health and less likely to access health services. PMID:26050155

  8. Security, development and human rights: normative, legal and policy challenges for the international drug control system.

    Science.gov (United States)

    Barrett, Damon

    2010-03-01

    This commentary addresses some of the challenges posed by the broader normative, legal and policy framework of the United Nations for the international drug control system. The 'purposes and principles' of the United Nations are presented and set against the threat based rhetoric of the drug control system and the negative consequences of that system. Some of the challenges posed by human rights law and norms to the international drug control system are also described, and the need for an impact assessment of the current system alongside alternative policy options is highlighted as a necessary consequence of these analyses. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  9. First Approval of Improved Medical Device Conditional on Use-Result Survey in Japan - Regulatory Review of Polymer-Free Drug-Coated BioFreedom Coronary Stent.

    Science.gov (United States)

    Konishi, Akihide; Ho, Mami; Shirai, Yuko; Shirato, Haruki

    2018-05-25

    A prospective randomized clinical trial showed that the BioFreedom stent (Biosensors International), which is a polymer-free and carrier-free drug-coated stent, was significantly superior to a bare-metal stent (BMS) in patients at high bleeding risk who were receiving a 1-month course of dual antiplatelet therapy (DAPT). However, the stent thrombosis rate (2.01% for BioFreedom vs. 2.20% for BMS) was 4-6-fold higher than that of approved drug-eluting stents based on real-world data in Japan. Furthermore, the frequency of stent thrombosis at more than 1 month with the BioFreedom stent was slightly higher than that at less than 1 month. This result suggested that it would not be acceptable to stop DAPT universally at 1 month. Thus, the target patients for the BioFreedom stent are unspecified patients at high bleeding risk needing to continue DAPT for as long as necessary in Japan. Therefore, based on the pre- and post-marketing balance of medical devices regulations, regulatory approval was given for unspecified patients conditionally upon real-world data collection of 2,000 patients with a Use-Results Survey, instead of conducting additional pre-marketing clinical trial(s). The Use-Results Survey System is part of a strategy to expedite patients' access to innovative medical devices and to accelerate the development of medical devices.

  10. 78 FR 68497 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2013-11-14

    ... are trading, the proposed rule change seeks to create less of a disconnect if the ``primary'' market... connected to the marketplace. B. Self-Regulatory Organization's Statement on Burden on Competition This...

  11. 78 FR 56762 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and...

    Science.gov (United States)

    2013-09-13

    ... innovative pricing strategy. The Exchange notes that if the proposal results in a modest percentage increase... may apply to Market Makers including marketing fees, Options Regulatory Fees, market data, and...

  12. Low doses of ionizing radiation: Biological effects and regulatory control. Invited papers and discussions. Proceedings of an international conference

    International Nuclear Information System (INIS)

    1998-01-01

    The levels and biological effects resulting from exposure to ionizing radiation are continuously reviewed by the United Nations Committee on the Effects of Atomic Radiation (UNSCEAR). Since its creation in 1928, the International Commission on Radiological Protection (ICRP) has issued recommendations on protection against ionizing radiation. The UNSCEAR estimates and the ICRP recommendations have served as the basis for national and international safety standards on radiation safety, including those developed by the International Atomic Energy Agency (IAEA) and the World Health Organization (WHO). Concerning health effects of low doses of ionizing radiation, the international standards are based on the plausible assumption that, above the unavoidable background radiation dose, the probability of effects increases linearly with dose, i.e. on a 'linear, no threshold' (LNT) assumption. However, in recent years the biological estimates of health effects of low doses of ionizing radiation and the regulatory approach to the control of low level radiation exposure have been much debated. To foster information exchange on the relevant issues, an International Conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, jointly sponsored by the IAEA and WHO in co-operation with UNSCEAR, was held from 17-21 November 1997 at Seville, Spain. These Proceedings contain the invited special reports, keynote papers, summaries of discussions, session summaries and addresses presented at the opening and closing of the Conference

  13. A comparative analysis of drug safety withdrawals in the UK and the US (1971-1992): implications for current regulatory thinking and policy.

    Science.gov (United States)

    Abraham, John; Davis, Courtney

    2005-09-01

    By going beyond individual case studies and solely quantitative surveys, this paper systematically examines why there were over twice as many new prescription drugs withdrawn from the market on grounds of safety in the UK as there were in the US between 1971 and 1992. Drawing on interviews with regulators, industry scientists and others involved, and on regulatory data never before accessed outside governments and companies, five key hypotheses which might explain this difference in drug safety withdrawals are analysed. These are: (1) simply because the UK approved more new drugs than the US; (2) because of an industrial corporate strategy to seek approval of 'less safe' drugs in the UK earlier; (3) because British regulators were more vigilant at spotting post-marketing safety problems than their US counterparts; (4) because the slowness of the US in approving new drugs enabled regulators there to learn from, and avoid, safety problems that had already emerged in the UK or European market; and (5) because more stringent regulation in the US meant that they approved fewer unsafe drugs on to the market in the first place. It is concluded that the main explanation for fewer drug safety withdrawals in the US is that the regulatory agency there applied more stringent pre-market review and/or standards, which took longer than UK regulatory checks, but prevented unsafe drugs marketed in the UK from entering the US market. Contrary to the claims frequently made by the pharmaceutical industry and regulatory agencies on both sides of the Atlantic, these results imply that it is likely that acceleration of regulatory review times in the US and the UK since the early 1990s is compromising drug safety.

  14. Introduction of direct-to-consumer advertising of prescription drugs in Canada: an opinion survey on regulatory policy.

    Science.gov (United States)

    Mintzes, Barbara; Barer, Morris; Lexchin, Joel; Bassett, Ken L

    2005-06-01

    Canada is strongly influenced by US cross-border direct-to-consumer advertising (DTCA) and has held consultations to discuss introduction of DTCA since 1996. This article describes a survey of Canadian drug policy experts carried out in 2001, during one such legislative review. The survey results are compared to more recent DTCA policy developments. We recruited key informants on pharmaceutical policy to complete a faxed questionnaire that queried their opinions on DTCA information quality, effects on drug and health care use, and regulatory issues. Respondents were asked about the evidence they had used to back their opinions. Analysis was descriptive. Of 79 identified potential participants, 60 (76%) participated, 40% of whom were from federal and provincial government; 3% were private insurers; 18%, 15%, and 8% were from health professional groups, consumer groups, and patient groups, respectively; 8% and 7% were from pharmaceutical and advertising industries, respectively. Opinions were highly polarized on the effects of DTCA on drug and health care use. Advertising and pharmaceutical industry respondents were generally positive, public sector, health professional and consumer groups generally negative. Over 80% believed DTCA leads to higher private and public drug costs and more frequent physician visits. Fewer judged billboards or television to be appropriate media for DTCA than magazines or the Internet, and most believed that children and adolescents should not be targeted. Given the polarization observed within this survey, we examined how DTCA policy has evolved in Canada since 2001. The federal government has legislative authority over DTCA, but bears few of the additional costs potentially incurred through policy change. These fall to the provinces, which provide an eroding patchwork of public coverage for prescription drugs in the face of rapidly increasing costs. No new federal legislation has been tabled since 2001. However, considerable shifts in

  15. A Multiple Indicators Multiple Causes (MIMIC) model of internal barriers to drug treatment in China.

    Science.gov (United States)

    Qi, Chang; Kelly, Brian C; Liao, Yanhui; He, Haoyu; Luo, Tao; Deng, Huiqiong; Liu, Tieqiao; Hao, Wei; Wang, Jichuan

    2015-03-01

    Although evidence exists for distinct barriers to drug abuse treatment (BDATs), investigations of their inter-relationships and the effect of individual characteristics on the barrier factors have been sparse, especially in China. A Multiple Indicators Multiple Causes (MIMIC) model is applied for this target. A sample of 262 drug users were recruited from three drug rehabilitation centers in Hunan Province, China. We applied a MIMIC approach to investigate the effect of gender, age, marital status, education, primary substance use, duration of primary drug use, and drug treatment experience on the internal barrier factors: absence of problem (AP), negative social support (NSS), fear of treatment (FT), and privacy concerns (PC). Drug users of various characteristics were found to report different internal barrier factors. Younger participants were more likely to report NSS (-0.19, p=0.038) and PC (-0.31, p<0.001). Compared to other drug users, ice users were more likely to report AP (0.44, p<0.001) and NSS (0.25, p=0.010). Drug treatment experiences related to AP (0.20, p=0.012). In addition, differential item functioning (DIF) occurred in three items when participant from groups with different duration of drug use, ice use, or marital status. Individual characteristics had significant effects on internal barriers to drug treatment. On this basis, BDAT perceived by different individuals could be assessed before tactics were utilized to successfully remove perceived barriers to drug treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Restrictions on antimicrobial use in food animal production: an international regulatory and economic survey

    Science.gov (United States)

    2013-01-01

    Background The administration of antimicrobial drugs to food animals at low doses for extended durations for growth promotion and disease prevention has been linked to the global health crisis of antimicrobial resistance. Internationally, multiple jurisdictions have responded by restricting antimicrobial use for these purposes, and by requiring a veterinary prescription to use these drugs in food animals. Opponents of these policies have argued that restrictions have been detrimental to food animal production where they have been adopted. Methods We surveyed the antimicrobial use policies of 17 political jurisdictions outside of the United States with respect to growth promotion, disease prevention, and veterinary oversight, and reviewed the available evidence regarding their production impacts, including measures of animal health. Jurisdictions were included if they were a top-five importer of a major U.S. food animal product in 2011, as differences between the policies of the U.S. and other jurisdictions may lead to trade barriers to U.S. food animal product exports. Jurisdictions were also included if information on their policies was publicly available in English. We searched the peer-reviewed and grey literatures and corresponded with jurisdictions’ U.S. embassies, regulators, and local experts. Results Jurisdictions were categorized by whether they prohibit use of antimicrobials for growth promotion and/or use of antimicrobials without a veterinary prescription. Of the 17 jurisdictions surveyed, six jurisdictions have prohibited both types of use, five jurisdictions have prohibited one use but not the other use, and five jurisdictions have not prohibited either use, while information was not available for one jurisdiction. Data on the production impacts of these prohibitions were limited, although available data, especially from Denmark and Sweden, suggest that restrictions on growth promotion use can be implemented with minimal production consequences

  17. Restrictions on antimicrobial use in food animal production: an international regulatory and economic survey.

    Science.gov (United States)

    Maron, Dina Fine; Smith, Tyler J S; Nachman, Keeve E

    2013-10-16

    The administration of antimicrobial drugs to food animals at low doses for extended durations for growth promotion and disease prevention has been linked to the global health crisis of antimicrobial resistance. Internationally, multiple jurisdictions have responded by restricting antimicrobial use for these purposes, and by requiring a veterinary prescription to use these drugs in food animals. Opponents of these policies have argued that restrictions have been detrimental to food animal production where they have been adopted. We surveyed the antimicrobial use policies of 17 political jurisdictions outside of the United States with respect to growth promotion, disease prevention, and veterinary oversight, and reviewed the available evidence regarding their production impacts, including measures of animal health. Jurisdictions were included if they were a top-five importer of a major U.S. food animal product in 2011, as differences between the policies of the U.S. and other jurisdictions may lead to trade barriers to U.S. food animal product exports. Jurisdictions were also included if information on their policies was publicly available in English. We searched the peer-reviewed and grey literatures and corresponded with jurisdictions' U.S. embassies, regulators, and local experts. Jurisdictions were categorized by whether they prohibit use of antimicrobials for growth promotion and/or use of antimicrobials without a veterinary prescription. Of the 17 jurisdictions surveyed, six jurisdictions have prohibited both types of use, five jurisdictions have prohibited one use but not the other use, and five jurisdictions have not prohibited either use, while information was not available for one jurisdiction. Data on the production impacts of these prohibitions were limited, although available data, especially from Denmark and Sweden, suggest that restrictions on growth promotion use can be implemented with minimal production consequences. A majority of leading U.S. trade

  18. Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies

    Science.gov (United States)

    Prugger, Christof; Doshi, Peter; Ostrowski, Kerstin; Witte, Thomas; Hüsgen, Dieter; Keil, Ulrich

    2017-01-01

    Objectives To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act. Design Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10. Setting Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany. Main outcome measures Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions. Results Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals. Conclusions Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are

  19. The regulatory consequences of Publication 60 of the ICRP (International Commission on Radiological Protection)

    International Nuclear Information System (INIS)

    Sugier, Annie

    1992-01-01

    The system of radiological protection recommended by the ICRP for future and existing proposed and continuing practices is based on the following general principles: justification, optimisation and limitation of exposure levels. This means that no practice involving exposures to radiation should be adopted unless it produces sufficient benefit to the exposed individuals or to the society to offset the radiation detriment it causes. In relation to any particular source within a practice, the magnitude of individual doses, the number of people exposed, and the likelihood of incurring exposures where these are not certain to be received should all be kept as low as reasonably achievable, economic and social factors being taken into account. The exposure of individuals resulting from the combination of all the relevant practices should be subject to dose limits, or to some control of risk in the case of potential exposures. The system for radiological protection and the values of the limits associated with it, are related the state of knowledge of the effects of radiation. This explains the periodic revision of the corresponding regulatory texts. In a field of such complexity, concerned by disciplines as diverse as medicine, biology, chemistry, statistics, etc., the question naturally arises as to which authority has the capacity to determine an agreed policy. As far as the European Community is concerned, the basic standards related to radiation protection are the subject of Directives which have to be incorporated into national laws by each member state. These directives are under review taking into account explicitly the ICRP recommendations. International agencies whose mission is concerned with the effects of ionising radiation, publish also basic standards related to radiological protection which are not imposed to the participating states except when they collaborate with those bodies, and which mainly act as international references. Such norms also comply with

  20. Imprecise Frequency Descriptors and the Miscomprehension of Prescription Drug Advertising: Public Policy and Regulatory Implications.

    Science.gov (United States)

    Davis, Joel J.

    1999-01-01

    Explores the communicative effectiveness of imprecise frequency descriptors within the context of consumer prescription drug advertising. Conducts two separate studies using a total sample of 147 adults. Finds that consumers are unable to accurately estimate the relative likelihood of side effect occurrence when a list of side effects are preceded…

  1. Steps towards the international regulatory acceptance of non-animal methodology in safety assessment.

    Science.gov (United States)

    Sewell, Fiona; Doe, John; Gellatly, Nichola; Ragan, Ian; Burden, Natalie

    2017-10-01

    The current animal-based paradigm for safety assessment must change. In September 2016, the UK National Centre for Replacement, Refinement and Reduction of Animals in Research (NC3Rs) brought together scientists from regulatory authorities, academia and industry to review progress in bringing new methodology into regulatory use, and to identify ways to expedite progress. Progress has been slow. Science is advancing to make this possible but changes are necessary. The new paradigm should allow new methodology to be adopted once it is developed rather than being based on a fixed set of studies. Regulatory authorities can help by developing Performance-Based Standards. The most pressing need is in repeat dose toxicology, although setting standards will be more complex than in areas such as sensitization. Performance standards should be aimed directly at human safety, not at reproducing the results of animal studies. Regulatory authorities can also aid progress towards the acceptance of non-animal based methodology by promoting "safe-haven" trials where traditional and new methodology data can be submitted in parallel to build up experience in the new methods. Industry can play its part in the acceptance of new methodology, by contributing to the setting of performance standards and by actively contributing to "safe-haven" trials. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. 76 FR 61438 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Proposed Rule...

    Science.gov (United States)

    2011-10-04

    ... clarify that 2102(e) applies to trading halts in new derivative securities, so as to not be confused with... derivative securities products when a temporary interruption occurs in the calculation or wide dissemination... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65425; File No. SR-ISE-2011-61] Self-Regulatory...

  3. 77 FR 16883 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

    Science.gov (United States)

    2012-03-22

    ...) (noting that the Chicago Mercantile Exchange moved the S&P 500[supreg] futures contract's settlement value... related market disruptions during that period in connection with the dual a.m./p.m.-settlement.\\18..., routine oversight inspections of the Exchange's regulatory programs by the Commission have not uncovered...

  4. 78 FR 69468 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and...

    Science.gov (United States)

    2013-11-19

    ... provide that in situations of a regulatory halt, trading pause or market-wide trading halt, a Post-Halt... situation of a halt pursuant to Rule 504(a), just as today, the Post-Halt Notification will continue to be..., Securities and Exchange Commission, 100 F Street NE., Washington, DC 20549-1090. All submissions should refer...

  5. European Union International Cooperation to Improve Regulatory Effectiveness in Nuclear Safety

    International Nuclear Information System (INIS)

    Stockmann, Y.

    2016-01-01

    The European Union (EU) promotes a high level of nuclear safety worldwide, through the ''Instrument for Nuclear Safety Cooperation'' (INSC) since 2007. The INSC builds on the experience gained under the completed ''Technical Assistance to the Commonwealth of Independent States'' Programme (TACIS) from 1991. Development and strengthening of national Regulatory Authorities’ capabilities is a key activity in achieving the INSC goals, in particular in countries with or embarking on nuclear power. Specific partner countries under INSC include countries of all types of maturity in the nuclear technology, with mature countries such as Brazil, Mexico and Ukraine, countries with waste and mining issues, but no direct intention of embarking on nuclear power such as Georgia, Mongolia, Tajikistan, Kyrgyzstan and Tanzania and countries planning to embark on nuclear power such as Belarus, Egypt, Jordan and Vietnam. For new projects, the main focus is on the neighbourhood of the EU. The EU cooperation within INSC encompasses measures to support the promotion of high standards in radiation protection, radioactive waste management, decommissioning, remediation of contaminated sites, and efficient and effective safeguards of nuclear material. The INSC regulatory support is aimed at continuous assistance to Nuclear Regulatory Authorities (NRAs), including their technical support organisations (TSOs), in order to reinforce the regulatory framework, notably concerning licensing activities.

  6. 78 FR 47041 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

    Science.gov (United States)

    2013-08-02

    ..., ISE believes that this should dispel any concerns regarding market manipulation. By extension, ISE... Agreement, dated June 20, 1994. The members of the ISG include all of the U.S. registered stock and options..., Inc., Chicago Stock Exchange, Inc., Financial Industry Regulatory Authority, NASDAQ Stock Market LLC...

  7. 77 FR 74905 - Self-Regulatory Organizations; Miami International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2012-12-18

    ... classes that the Market Maker has the general obligation to attract order flow to the Exchange. MIAX will... accordance with instructions received from the applicable Primary Lead Market Maker ``PLMM'' or Lead Market... order that was routed. Regulatory Fees A. Sales Value Fee The Sales Value Fee \\7\\ is assessed by the...

  8. 76 FR 20752 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2011-04-13

    ...). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance of the... whole number, resulting in an implied number of users based on quotes. Market makers are invoiced on a... number of implied users based on quotes. \\5\\ See Exchange Act Release No. 56721 (October 30, 2007), 72 FR...

  9. 76 FR 77881 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2011-12-14

    ...). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance of the... million and rounded up to the nearest whole number, resulting in an implied number of users based on... that logged into the system, or (b) the number of implied users based on quotes. \\5\\ See Exchange Act...

  10. 78 FR 62901 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2013-10-22

    ... per contract from its prior rate of $0.05 per contract. See Securities Exchange Act Release No. 69768... similar products.\\13\\ \\13\\ At least one other exchange currently trades foreign currency options. While... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70647; File No. SR-ISE-2013-50] Self-Regulatory...

  11. 78 FR 70382 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2013-11-25

    ..., with respect to index options, restrictions on exercise may be in effect until the opening of business... security of an option contract that is scheduled to be released just after the close on the business day... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70900; File No. SR-ISE-2013-58] Self-Regulatory...

  12. A Review of International Telecommunications Industry Issues, Structure, and Regulatory Problems.

    Science.gov (United States)

    Cole, Jack E.; And Others

    Industry structure studies prior to 1968 are briefly reviewed, and an overview of industrial and technological developments up to the present is provided through synopses of more recent studies. Areas covered include overseas telephone and record carriers; the creation of the Communications Satellite Corporation; the current regulatory and…

  13. The temporal relationship between drug supply indicators: an audit of international government surveillance systems

    Science.gov (United States)

    Werb, Dan; Kerr, Thomas; Nosyk, Bohdan; Strathdee, Steffanie; Montaner, Julio; Wood, Evan

    2013-01-01

    Objectives Illegal drug use continues to be a major threat to community health and safety. We used international drug surveillance databases to assess the relationship between multiple long-term estimates of illegal drug price and purity. Design We systematically searched for longitudinal measures of illegal drug supply indicators to assess the long-term impact of enforcement-based supply reduction interventions. Setting Data from identified illegal drug surveillance systems were analysed using an a priori defined protocol in which we sought to present annual estimates beginning in 1990. Data were then subjected to trend analyses. Main outcome measures Data were obtained from government surveillance systems assessing price, purity and/or seizure quantities of illegal drugs; systems with at least 10 years of longitudinal data assessing price, purity/potency or seizures were included. Results We identified seven regional/international metasurveillance systems with longitudinal measures of price or purity/potency that met eligibility criteria. In the USA, the average inflation-adjusted and purity-adjusted prices of heroin, cocaine and cannabis decreased by 81%, 80% and 86%, respectively, between 1990 and 2007, whereas average purity increased by 60%, 11% and 161%, respectively. Similar trends were observed in Europe, where during the same period the average inflation-adjusted price of opiates and cocaine decreased by 74% and 51%, respectively. In Australia, the average inflation-adjusted price of cocaine decreased 14%, while the inflation-adjusted price of heroin and cannabis both decreased 49% between 2000 and 2010. During this time, seizures of these drugs in major production regions and major domestic markets generally increased. Conclusions With few exceptions and despite increasing investments in enforcement-based supply reduction efforts aimed at disrupting global drug supply, illegal drug prices have generally decreased while drug purity has generally

  14. The temporal relationship between drug supply indicators: an audit of international government surveillance systems.

    Science.gov (United States)

    Werb, Dan; Kerr, Thomas; Nosyk, Bohdan; Strathdee, Steffanie; Montaner, Julio; Wood, Evan

    2013-09-30

    Illegal drug use continues to be a major threat to community health and safety. We used international drug surveillance databases to assess the relationship between multiple long-term estimates of illegal drug price and purity. We systematically searched for longitudinal measures of illegal drug supply indicators to assess the long-term impact of enforcement-based supply reduction interventions. Data from identified illegal drug surveillance systems were analysed using an a priori defined protocol in which we sought to present annual estimates beginning in 1990. Data were then subjected to trend analyses. Data were obtained from government surveillance systems assessing price, purity and/or seizure quantities of illegal drugs; systems with at least 10 years of longitudinal data assessing price, purity/potency or seizures were included. We identified seven regional/international metasurveillance systems with longitudinal measures of price or purity/potency that met eligibility criteria. In the USA, the average inflation-adjusted and purity-adjusted prices of heroin, cocaine and cannabis decreased by 81%, 80% and 86%, respectively, between 1990 and 2007, whereas average purity increased by 60%, 11% and 161%, respectively. Similar trends were observed in Europe, where during the same period the average inflation-adjusted price of opiates and cocaine decreased by 74% and 51%, respectively. In Australia, the average inflation-adjusted price of cocaine decreased 14%, while the inflation-adjusted price of heroin and cannabis both decreased 49% between 2000 and 2010. During this time, seizures of these drugs in major production regions and major domestic markets generally increased. With few exceptions and despite increasing investments in enforcement-based supply reduction efforts aimed at disrupting global drug supply, illegal drug prices have generally decreased while drug purity has generally increased since 1990. These findings suggest that expanding efforts at

  15. Modeling Attitude towards Drug Treament: The Role of Internal Motivation, External Pressure, and Dramatic Relief

    OpenAIRE

    Conner, Bradley T.; Longshore, Douglas; Anglin, M. Douglas

    2008-01-01

    Motivation for change has historically been viewed as the crucial element affecting responsiveness to drug treatment. Various external pressures, such as legal coercion, may engender motivation in an individual previously resistant to change. Dramatic relief may be the change process that is most salient as individuals internalize such external pressures. Results of structural equation modeling on data from 465 drug users (58.9% male; 21.3% Black, 34.2% Hispanic/Latino, and 35.1% White) enter...

  16. 75 FR 32977 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2010-06-10

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed... Permit Opening Transactions by Market Makers To Accommodate Closing Transactions of Other Market... International Securities Exchange, LLC (``Exchange'' or ``ISE'') filed with the Securities and Exchange...

  17. Information on new drugs at market entry: retrospective analysis of health technology assessment reports versus regulatory reports, journal publications, and registry reports.

    Science.gov (United States)

    Köhler, Michael; Haag, Susanne; Biester, Katharina; Brockhaus, Anne Catharina; McGauran, Natalie; Grouven, Ulrich; Kölsch, Heike; Seay, Ulrike; Hörn, Helmut; Moritz, Gregor; Staeck, Kerstin; Wieseler, Beate

    2015-02-26

    When a new drug becomes available, patients and doctors require information on its benefits and harms. In 2011, Germany introduced the early benefit assessment of new drugs through the act on the reform of the market for medicinal products (AMNOG). At market entry, the pharmaceutical company responsible must submit a standardised dossier containing all available evidence of the drug's added benefit over an appropriate comparator treatment. The added benefit is mainly determined using patient relevant outcomes. The "dossier assessment" is generally performed by the Institute for Quality and Efficiency in Health Care (IQWiG) and then published online. It contains all relevant study information, including data from unpublished clinical study reports contained in the dossiers. The dossier assessment refers to the patient population for which the new drug is approved according to the summary of product characteristics. This patient population may comprise either the total populations investigated in the studies submitted to regulatory authorities in the drug approval process, or the specific subpopulations defined in the summary of product characteristics ("approved subpopulations"). To determine the information gain from AMNOG documents compared with non-AMNOG documents for methods and results of studies available at market entry of new drugs. AMNOG documents comprise dossier assessments done by IQWiG and publicly available modules of company dossiers; non-AMNOG documents comprise conventional, publicly available sources-that is, European public assessment reports, journal publications, and registry reports. The analysis focused on the approved patient populations. Retrospective analysis. All dossier assessments conducted by IQWiG between 1 January 2011 and 28 February 2013 in which the dossiers contained suitable studies allowing for a full early benefit assessment. We also considered all European public assessment reports, journal publications, and registry reports

  18. Addressing the challenge of high-priced prescription drugs in the era of precision medicine : a systematic review of drug life cycles, therapeutic drug markets and regulatory frameworks.

    NARCIS (Netherlands)

    van der Gronde, T.; Uyl-de Groot, Carin A; Pieters, A.H.L.M.

    2017-01-01

    Context. Recent public outcry has highlighted the rising cost of prescription drugs worldwide, which in several disease areas outpaces other health care expenditures and results in a suboptimal global availability of essential medicines. Method. A systematic review of Pubmed, the Financial Times,

  19. Addressing the challenge of high-priced prescription drugs in the era of precision medicine : A systematic review of drug life cycles, therapeutic drug markets and regulatory frameworks

    NARCIS (Netherlands)

    Gronde, T.V. (Toon van der); C.A. Uyl-de Groot (Carin); Pieters, T. (Toine)

    2017-01-01

    markdownabstractCONTEXT: Recent public outcry has highlighted the rising cost of prescription drugs worldwide, which in several disease areas outpaces other health care expenditures and results in a suboptimal global availability of essential medicines. METHOD: A systematic review of Pubmed, the

  20. International conference on strengthening of nuclear safety in Eastern Europe. Armenian Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    Nersesyan, V.

    1999-01-01

    The status of the Armenian Nuclear Regulatory Authority (ANRA) are described in detail with its main task and responsibilities concerning regulations and surveillance of nuclear and radiation safety. The following issues are presented: nuclear legislation; inspection activities; licensing of significant safety related modifications and modernization of NPPs; incidents at NPPs; personnel training; emergency planning; surveillance of nuclear materials; radioactive waste management; and plan of the ANRA perspective development

  1. Study on CPPNM Interpretation of the Physical Protection Regulatory Aspects for International Transport of Nuclear Material

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Woo-jin; Yang, Seong-hyo; Hyung, Sang-chul [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2015-05-15

    Nuclear energy has been regulated by various international agreements or treaties due to the potential dangers. In case of export or import of nuclear material, it is important to comply with international norms and domestic laws related to nonproliferation and physical protection of nuclear material. Because, if non-compliant, it can be taken nuclear sanctions from the international community, and thus the domestic nuclear activities can be under a negative impact. Recently, international interests in nuclear security have been increased, it has become very sensitive to whether or not to join, and to comply with international treaties during international transportation of nuclear materials. Currently it is not discussed yet how to present and interpret the relevant provisions in CPPNM. However, it is necessary to prepare for the dispute among the parties that we don't know when it happens.

  2. 76 FR 47627 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2011-08-05

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to Two Market Data Feeds August 1, 2011. Pursuant to Section 19(b)(1) of the... on August 1, 2011, the International Securities Exchange, LLC (the ``Exchange'' or the ``ISE'') filed...

  3. 76 FR 51075 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Granting Approval to...

    Science.gov (United States)

    2011-08-17

    ... Organizations; International Securities Exchange, LLC; Order Granting Approval to a Proposed Rule Change Relating to Appointments to Competitive Market Makers August 11, 2011. I. Introduction On June 10, 2011, the International Securities Exchange, LLC (the ``Exchange'' or the ``ISE'') filed with the Securities...

  4. 77 FR 37722 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2012-06-22

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Eliminate the Rules and Fees Related to the Second Market June 18, 2012. Pursuant to...\\ notice is hereby given that on June 6, 2012, the International Securities Exchange, LLC (the ``Exchange...

  5. 78 FR 24271 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2013-04-24

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend the Market Maker Plus Rebate Program April 18, 2013. Pursuant to Section 19(b)(1... hereby given that on April 10, 2013, the International Securities Exchange, LLC (the ``Exchange'' or the...

  6. 77 FR 1757 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2012-01-11

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to a Market Maker Incentive Plan for Foreign Currency Options January 5, 2012...,\\2\\ notice is hereby given that on December 28, 2011, the International Securities Exchange, LLC (the...

  7. 78 FR 17988 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2013-03-25

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Regarding Market Maker Quoting Requirements March 19, 2013. Pursuant to Section 19(b)(1) of... given that on March 5, 2013, the International Securities Exchange, LLC (the ``Exchange'' or the ``ISE...

  8. 78 FR 45580 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2013-07-29

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change to Amend Certain Market Maker Fees July 23, 2013. Pursuant to Section 19(b)(1) of the... hereby given that on July 11, 2013, the International Securities Exchange, LLC (the ``Exchange'' or the...

  9. 76 FR 32382 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2011-06-06

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to Second Market Fees May 27, 2011. Pursuant to Section 19(b)(1) of the Securities..., 2011, the International Securities Exchange, LLC (the ``Exchange'' or the ``ISE'') filed with the...

  10. 77 FR 31680 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2012-05-29

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend the Qualification Standards for Market Makers To Receive a Rebate May 22, 2012...-4 thereunder,\\2\\ notice is hereby given that on May 15, 2012, the International Securities Exchange...

  11. 76 FR 56832 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2011-09-14

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to a New Market Data Feed September 8, 2011. Pursuant to Section 19(b)(1) of the... on August 31, 2011, the International Securities Exchange, LLC (the ``Exchange'' or the ``ISE...

  12. 77 FR 37944 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

    Science.gov (United States)

    2012-06-25

    ... Organizations; International Securities Exchange, LLC; Notice of Filing of Proposed Rule Change To Allow Competitive Market Makers To Use Their Membership Points To Enter Multiple Quotes in an Options Class June 19... 19b-4 thereunder,\\2\\ notice is hereby given that on June 6, 2012, the International Securities...

  13. 76 FR 37863 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

    Science.gov (United States)

    2011-06-28

    ... Organizations; International Securities Exchange, LLC; Notice of Filing of Proposed Rule Change Relating to Appointments to Competitive Market Makers June 22, 2011. Pursuant to Section 19(b)(1) of the Securities... that on June 10, 2011, the International Securities Exchange, LLC (the ``Exchange'' or the ``ISE...

  14. 75 FR 42812 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2010-07-22

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to a Market Maker Incentive Plan for Foreign Currency Options July 15, 2010..., \\2\\ notice is hereby given that on June 30, 2010, International Securities Exchange, LLC (``ISE'' or...

  15. 76 FR 64417 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2011-10-18

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to Competitive Market Maker Trading Rights October 12, 2011. Pursuant to Section...\\ notice is hereby given that on October 3, 2011, the International Securities Exchange, LLC (the...

  16. 77 FR 34436 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

    Science.gov (United States)

    2012-06-11

    ... Organizations; International Securities Exchange, LLC; Notice of Filing of Proposed Rule Change To Temporarily... International Securities Exchange, LLC (the ``Exchange'' or the ``ISE'') filed with the Securities and Exchange... Clearing and Outsourcing Solutions, Inc. (``Apex Clearing'') as an ISE member organization, subject to Apex...

  17. Sexual violence: feminist developments, rape myths and the international regulatory response

    OpenAIRE

    Tardón Recio, Bárbara

    2017-01-01

    Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Filosofía y Letras, Instituto Universitario de Estudios de la Mujer. Fecha de lectura: 29-09-2017 Making use of a feminist and human rights-based theoretical framework, this doctoral thesis reveals the isolation experienced by women victims of sexual violence over the last 30 years in Spain, despite the positive developments in this realm and the existence of a regulatory framework specifically addressi...

  18. International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes

    DEFF Research Database (Denmark)

    Bal-Price, Anna; Crofton, Kevin M.; Leist, Marcel

    2015-01-01

    . The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified...... as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment...

  19. 75 FR 50015 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2010-08-16

    ...''), Halliburton Company (``HAL''), International Business Machines Corporation (``IBM''), The Coca-Cola [[Page...Shares Russell 2000 (``IWM''), Financial Select Sector SPDR (``XLF''), Apple, Inc. (``AAPL''), General... Company (``F''), Direxion Shares Financial Bull (``FAS''), Direxion Shares Financial Bear (``FAZ''), First...

  20. 75 FR 6421 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2010-02-09

    ... Broadcom Corp. BTU Peabody Energy Corp. BX Blackstone Group LP. CAL Continental Airlines Inc. CF CF... Inc. HON Honeywell International Inc. JOYG Joy Global Inc. JWN Nordstrom Inc. KFT Kraft Foods Inc...

  1. The Regulatory Framework Across International Jurisdictions for Risks Associated with Consumption of Botanical Food Supplements

    NARCIS (Netherlands)

    Low, Teng Yong; Wong, Kwok Onn; Yap, Adelene L.L.; Haan, De Laura H.J.; Rietjens, Ivonne M.C.M.

    2017-01-01

    Dietary supplements, including those containing botanical ingredients and botanical-derived compounds, have been marketed to consumers globally for many decades. However, the legislative framework for such products remains inconsistent across jurisdictions internationally. This study aims to

  2. Global trade and assisted reproductive technologies: regulatory challenges in international surrogacy.

    Science.gov (United States)

    Nelson, Erin

    2013-01-01

    International surrogacy is an increasingly common phenomenon and an important global health challenge. Legal rules are a key consideration for the participants in international surrogacy arrangements. In some cases the law can help to resolve the complex issues that arise in this context, but it is important to consider the role played by law in contributing to the complex conflicts that such arrangements can generate. © 2013 American Society of Law, Medicine & Ethics, Inc.

  3. Regulatory Governance

    DEFF Research Database (Denmark)

    Kjær, Poul F.; Vetterlein, Antje

    2018-01-01

    Regulatory governance frameworks have become essential building blocks of world society. From supply chains to the regimes surrounding international organizations, extensive governance frameworks have emerged which structure and channel a variety of social exchanges, including economic, political...... by the International Transitional Administrations (ITAs) in Kosovo and Iraq as well as global supply chains and their impact on the garment industry in Bangladesh....

  4. A European regulatory perspective on cystic fibrosis: current treatments, trends in drug development and translational challenges for CFTR modulators.

    Science.gov (United States)

    Ponzano, Stefano; Nigrelli, Giulia; Fregonese, Laura; Eichler, Irmgard; Bertozzi, Fabio; Bandiera, Tiziano; Galietta, Luis J V; Papaluca, Marisa

    2018-06-30

    In this article we analyse the current authorised treatments and trends in early drug development for cystic fibrosis (CF) in the European Union for the time period 2000-2016. The analysis indicates a significant improvement in the innovation and development of new potential medicines for CF, shifting from products that act on the symptoms of the disease towards new therapies targeting the cause of CF. However, within these new innovative medicines, results for CF transmembrane conductance regulator (CFTR) modulators indicate that one major challenge for turning a CF concept product into an actual medicine for the benefit of patients resides in the fact that, although pre-clinical models have shown good predictability for certain mutations, a good correlation to clinical end-points or biomarkers ( e.g. forced expiratory volume in 1 s and sweat chloride) for all mutations has not yet been achieved. In this respect, the use of alternative end-points and innovative nonclinical models could be helpful for the understanding of those translational discrepancies. Collaborative endeavours to promote further research and development in these areas as well as early dialogue with the regulatory bodies available at the European competent authorities are recommended. Copyright ©ERS 2018.

  5. Use of Advanced Tsunami Hazard Assessment Techniques and Tsunami Source Characterizations in U.S. and International Nuclear Regulatory Activities

    Science.gov (United States)

    Kammerer, A. M.; Godoy, A. R.

    2009-12-01

    In response to the 2004 Indian Ocean Tsunami, as well as the anticipation of the submission of license applications for new nuclear facilities, the United States Nuclear Regulatory Commission (US NRC) initiated a long-term research program to improve understanding of tsunami hazard levels for nuclear power plants and other coastal facilities in the United States. To undertake this effort, the US NRC organized a collaborative research program jointly undertaken with researchers at the United States Geological Survey (USGS) and the National Oceanic and Atmospheric Administration (NOAA) for the purpose of assessing tsunami hazard on the Atlantic and Gulf Coasts of the United States. This study identified and modeled both seismic and landslide tsunamigenic sources in the near- and far-field. The results from this work are now being used directly as the basis for the review of tsunami hazard at potential nuclear plant sites. This application once again shows the importance that the earth sciences can play in addressing issues of importance to society. Because the Indian Ocean Tsunami was a global event, a number of cooperative international activities have also been initiated within the nuclear community. The results of US efforts are being incorporated into updated regulatory guidance for both the U.S. Nuclear Regulatory Commission and the United Nation’s International Atomic Energy Agency (IAEA). Coordinated efforts are underway to integrate state-of-the art tsunami warning tools developed by NOAA into NRC and IAEA activities. The goal of the warning systems project is to develop automated protocols that allow scientists at these agencies to have up-to-the minute user-specific information in hand shortly after a potential tsunami has been identified by the US Tsunami Warning System. Lastly, USGS and NOAA scientists are assisting the NRC and IAEA in a special Extra-Budgetary Program (IAEA EBP) on tsunami being coordinated by the IAEA’s International Seismic Safety

  6. Internalization, Trafficking, Intracellular Processing and Actions of Antibody-Drug Conjugates.

    Science.gov (United States)

    Xu, Shi

    2015-11-01

    This review discusses the molecular mechanism involved in the targeting and delivery of antibody-drug conjugates (ADCs), the new class of biopharmaceuticals mainly designed for targeted cancer therapy. this review goes over major progress in preclinical and clinical studies of ADCs, in the past 5 years. The pharmacokinetics and pharmacodynamics of ADCs involve multiple mechanisms, including internalization of ADCs by target cells, intracellular trafficking, release of conjugated drugs, and payload. These mechanisms actually jointly determine the efficacy of ADCs. Therefore, the optimization of ADCs should take them as necessary rationales.

  7. Regulatory and scientific frameworks for zoonosis control in Japan--contributing to International Health Regulations (2005).

    Science.gov (United States)

    Takahashi-Omoe, H; Omoe, K

    2009-12-01

    Zoonoses have earned recognition as the source of serious problems for both public and animal health throughout the world. Emerging infectious diseases have been occurring at an unprecedented rate since the 1970s and a large proportion of these diseases are considered zoonotic. To aid in controlling zoonoses, countermeasures have been strengthened against these diseases and are maintained at both national and international levels. Atypical example of this international effort can be found in the revised International Health Regulations (2005), known as the IHR (2005), which were instituted by the World Health Organization and have been implemented since 2007. In Japan, the appropriate Ministries have established frameworks for controlling zoonoses that employ both administrative and scientific approaches to fulfill the demands of the IHR (2005). In this paper, the authors present the Japanese framework for controlling zoonoses, as a useful example for global public and animal health management in coming years.

  8. Proceedings of the 13. International Workshop on Inspection Practices. 13. International Nuclear Regulatory Inspection Workshop - Appendix of Responses, 17-21 April 2016, Bruges, Belgium

    International Nuclear Information System (INIS)

    2017-01-01

    This appendix provides the complete compilation of responses received to the questionnaire issued in conjunction with the workshop announcements. The responses are provided as received, with changes made only to the formatting. The OECD Nuclear Energy Agency (NEA) Committee on Nuclear Regulatory Activities (CNRA) Working Group on Inspection Practices (WGIP) sponsored the 13. International Workshop on Nuclear Regulatory Inspection Activities. The workshop was hosted by the Bel V and FANC, in Bruges, Belgium on 17 -21 April 2016. The three workshop topics that were addressed were as follows: - Inspection Activities During the Transition from an Operating Reactor to a De-fueled Status with a Commitment to Cease Power Operation; - Inspection of Modifications; - The Inspectors' Role in the Enforcement Process. Each of the respondents was given the following instructions in relation to their response: - Only one response per country is required. If more than one person from your country is participating, please co-ordinate the responses accordingly. - Responses must be provided on separate sheet with clear identification of the questionnaire part and topic. For preparation of the workshop, participants were invited to supply their national inspection approaches used in inspection of events and incidents according to the surveys. Actual issues that were discussed during the workshop were generated by the topic leaders based on the responses submitted by participants with their registration forms. This formats helped to ensure that issues considered most important by the workshop participants were covered during the group discussions

  9. 77 FR 24752 - Self-Regulatory Organizations; EDGA Exchange, Inc.; EDGX Exchange, Inc.; International Securities...

    Science.gov (United States)

    2012-04-25

    ... Securities Holdings, Inc. (``ISE Holdings'') to a newly formed Swiss corporation, Eurex Global Derivatives AG... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66834; File Nos. SR-EDGA-2012-08; SR-EDGX-2012....; International Securities Exchange, LLC; Order Granting Approval of Proposed Rule Change Relating to a Corporate...

  10. 75 FR 42809 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2010-07-22

    ...''), International Business Machines Corporation (``IBM''), The Coca-Cola Company (``KO''), Las Vegas Sands Corp...Shares Russell 2000 (``IWM''), Financial Select Sector SPDR (``XLF''), Apple, Inc. (``AAPL''), General... Company (``F''), Direxion Shares Financial Bull (``FAS''), Direxion Shares Financial Bear (``FAZ''), First...

  11. 75 FR 7299 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving Proposed...

    Science.gov (United States)

    2010-02-18

    ... to the U.S. Exchange Holdings, Inc. Corporate Documents and International Securities Exchange Trust... change relating to the U.S. Exchange Holdings, Inc. (``U.S. Exchange Holdings'') Corporate Documents (as... Holdings purchased an ownership interest in Direct Edge by contributing cash and the marketplace then...

  12. 75 FR 42801 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Science.gov (United States)

    2010-07-22

    ... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed... at or under the threshold are charged the constituent's prescribed execution fee. This waiver applies... members to execute large-sized FX options orders on the Exchange in a manner that is cost effective. The...

  13. Regulatory Capacity Building in Romania – an International Nuclear Safety Cooperation between Norway, Romania and the IAEA 2013-2017

    International Nuclear Information System (INIS)

    Mattsson, H.

    2016-01-01

    The Romanian National Commission for Nuclear Activities Control (CNCAN), the Norwegian Radiation Protection Authority (NRPA), and the International Atomic Energy Agency (IAEA) is cooperating on a project named “Regional Excellence Project on Regulatory Capacity Building in Nuclear and Radiological Safety, Emergency Preparedness and Response in Romania“. The project started in the end of 2013 and will be completed in 2017. The project has a budget of 4.2 million euros, where 85% is covered by Norway Grants and 15% covered by Romania. Norway Grants is the contribution of Norway to reducing economical and social disparities and strengthening bilateral relations with 16 EU countries in Central and Southern Europe. The entire project is organised through an IAEA extra-budgetary programme. This project is a continuation of a similar project with the same partners that was successfully implemented in the period 2009-2011.

  14. Collaborative international research: ethical and regulatory issues pertaining to human biological materials at a South African institutional research ethics committee.

    Science.gov (United States)

    Sathar, Aslam; Dhai, Amaboo; van der Linde, Stephan

    2014-12-01

    Human Biological Materials (HBMs) are an invaluable resource in biomedical research. To determine if researchers and a Research Ethics Committee (REC) at a South African institution addressed ethical issues pertaining to HBMs in collaborative research with developed countries. Ethically approved retrospective cross-sectional descriptive audit. Of the 1305 protocols audited, 151 (11.57%) fulfilled the study's inclusion criteria. Compared to other developed countries, a majority of sponsors (90) were from the USA (p = 0.0001). The principle investigators (PIs) in all 151 protocols informed the REC of their intent to store HBMs. Only 132 protocols informed research participants (P ethical and regulatory issues pertaining to HBMs. There was a lack of congruence between the ethical guidelines of developed countries and their actions which are central to the access to HBMs in collaborative research. HBMs may be leaving South Africa without EPs and MTAs during the process of international collaborative research. © 2013 John Wiley & Sons Ltd.

  15. Does the Early Adopter of Drugs Exist? A Population Based Study of General Practitioners’ Prescribing of New Drugs.20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158

    DEFF Research Database (Denmark)

    Dybdahl, Torben; Andersen, Morten; Søndergaard, Jens

    2004-01-01

    20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158......20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158...

  16. Proceedings of the 13. International Workshop on Inspection Practices. 13. International Nuclear Regulatory Inspection Workshop, 17-21 April 2016, Bruges, Belgium

    International Nuclear Information System (INIS)

    Bens, Jan; De Boeck, Benoit; Wertelaers, An; Van Haesendonck, Michel; Barras, Pierre; Leblanc, Alexandre; Regan, Christopher; Smith, Paul; Kupila, Jukka; Crespo, Julio; Meskens, Gaston; Schneider, Matthias

    2017-01-01

    The main purpose of the workshop was to provide a forum for information exchange on the regulatory inspection activities. Participants had the opportunity to meet with their counterparts from other countries and organisations to discuss current and future issues on the selected topics. They developed conclusions regarding these issues and identified methods that may help to improve their own inspection programmes. The CNRA believes that an essential factor in ensuring the safety of nuclear installations is the continuing exchange and analysis of technical information and data. To facilitate this exchange the Committee has established working groups and groups of experts in specialised topics. The Working Group on Inspection Practices (WGIP) was formed in 1990 with the mandate '...to concentrate on the conduct of inspections and how the effectiveness of inspections could be evaluated..'. The WGIP facilitates the exchange of information and experience related to regulatory safety inspections between CNRA member countries. These proceedings cover the 13. International Nuclear Regulatory Inspection Workshop held by WGIP on regulatory inspection activities. This workshop, which is the 13. in a series, along with many other activities performed by the working group, is directed towards this goal. The consensus from participants at previous workshops noted that the value of meeting with people from other inspection organisations was one of the most important achievements. The focus of this workshop was on experience gained from regulatory inspection activities in three areas: - experience from the inspection activities during the transition from an operating reactor to a de-fueled status with a commitment to permanently cease power operations; - inspection of modifications; - the inspectors' role in the enforcement process. As part of the registration, participants were asked to respond to a questionnaire describing practices within their own countries on these topics

  17. Review of the International Atomic Energy Agency International database on reactor pressure vessel materials and US Nuclear Regulatory Commission/Oak Ridge National Laboratory embrittlement data base

    International Nuclear Information System (INIS)

    Wang, J.A.; Kam, F.B.K.

    1998-02-01

    The International Atomic Energy Agency (IAEA) has supported neutron radiation effects information exchange through meetings and conferences since the mid-1960s. Through an International Working Group on Reliability of Reactor Pressure Components, information exchange and research activities were fostered through the Coordinated Research Program (CRP) sponsored by the IAEA. The final CRP meeting was held in November 1993, where it was recommended that the IAEA coordinate the development of an International Database on Reactor Pressure Vessel Material (IDRPVM) as the first step in generating an International Database on Aging Management. The purpose of this study was to provide special technical assistance to the NRC in monitoring and evaluating the IAEA activities in developing the IAEA IDRPVM, and to compare the IDRPVM with the Nuclear Regulatory Commission (NRC) - Oak Ridge National Laboratory (ORNL) Power Reactor Embrittlement Data Base (PR-EDB) and provide recommendations for improving the PR-EDB. A first test version of the IDRPVM was distributed at the First Meeting of Liaison Officers to the IAEA IDRPVM, in November 1996. No power reactor surveillance data were included in this version; the testing data were mainly from CRP Phase III data. Therefore, because of insufficient data and a lack of power reactor surveillance data received from the IAEA IDRPVM, the comparison is made based only on the structure of the IDRPVM. In general, the IDRPVM and the EDB have very similar data structure and data format. One anticipates that because the IDRPVM data will be collected from so many different sources, quality assurance of the data will be a difficult task. The consistency of experimental test results will be an important issue. A very wide spectrum of material characteristics of RPV steels and irradiation environments exists among the various countries. Hence the development of embrittlement prediction models will be a formidable task. 4 refs., 2 figs., 4 tabs

  18. Impact of regulatory spin of pioglitazone on prescription of antidiabetic drugs among physicians in India: A multicentre questionnaire-based observational study

    Directory of Open Access Journals (Sweden)

    Aman Goyal

    2017-01-01

    Interpretation & conclusions: Majority of the physicians though were aware of the regulatory changes with regard to pioglitazone, but their prescribing patterns were not changed for this drug. However, it was being used at lower than the recommended dose. There is a need for generating more evidence through improved pharmacovigilance activities and large-scale population-based prospective studies regarding the safety issues of pioglitazone, so as to make effectual risk-benefit analysis for its continual use in T2DM.

  19. Regulatory Perspectives on Continuous Pharmaceutical Manufacturing: Moving From Theory to Practice: September 26-27, 2016, International Symposium on the Continuous Manufacturing of Pharmaceuticals.

    Science.gov (United States)

    Nasr, Moheb M; Krumme, Markus; Matsuda, Yoshihiro; Trout, Bernhardt L; Badman, Clive; Mascia, Salvatore; Cooney, Charles L; Jensen, Keith D; Florence, Alastair; Johnston, Craig; Konstantinov, Konstantin; Lee, Sau L

    2017-11-01

    Continuous manufacturing plays a key role in enabling the modernization of pharmaceutical manufacturing. The fate of this emerging technology will rely, in large part, on the regulatory implementation of this novel technology. This paper, which is based on the 2nd International Symposium on the Continuous Manufacturing of Pharmaceuticals, describes not only the advances that have taken place since the first International Symposium on Continuous Manufacturing of Pharmaceuticals in 2014, but the regulatory landscape that exists today. Key regulatory concepts including quality risk management, batch definition, control strategy, process monitoring and control, real-time release testing, data processing and management, and process validation/verification are outlined. Support from regulatory agencies, particularly in the form of the harmonization of regulatory expectations, will be crucial to the successful implementation of continuous manufacturing. Collaborative efforts, among academia, industry, and regulatory agencies, are the optimal solution for ensuring a solid future for this promising manufacturing technology. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  20. MODERN APPROACHES TO PUBLIC PROTECTION AGAINST INDOOR RADON. INTERNATIONAL REGULATORY EXPERIENCE

    Directory of Open Access Journals (Sweden)

    S. M. Kiselev

    2014-01-01

    Full Text Available Intensive worldwide researches of the public exposure to radon are carried out for over 30 years. According to numerous studies being performed in many countries, radon and its progenies contribute significantly in total dose to the public. At that, dose due to inhalation of radon and its progenies is higher than that induced by other radiation sources, including sources used in medicine and those occurring in the environment due to the nuclear fuel cycle activities. Prolonged internal exposure to the human‘s body induced by the radon decay products is one of the key factors in the development of the lung cancer pathology. The recent results of global epidemiological studies, aimed at the risk assessment of indoor radon-induced lung cancer, have initiated the need to improve approaches to the regulation of this problem. International organizations (such as WHO, IAEA, ICRP proposed a strategy of the public radiation protection against radon exposure and adapted this strategy to the up-to-date realities. The recent recommendations not only correct the radon activity concentration being limited in dwellings, but also change its status through converting the action level to the reference one. The strategies for limitation of the public exposure due to this component of natural radiation should be revised at the national level and an action plan for their implementation in the long term perspective should be developed. This paper deals with the key provisions of the recent international recommendations including approaches to regulate the public protection against radon exposure.

  1. Review of regulatory recommendations for orphan drug submissions in the Netherlands and Scotland : focus on the underlying pharmacoeconomic evaluations

    NARCIS (Netherlands)

    Vegter, Stefan; Rozenbaum, Mark H.; Postema, Roelien; Tolley, Keith; Postma, Maarten J.

    2010-01-01

    Background: Pharmacoeconomic evaluations of new drug therapies are often required for reimbursement or guidance decisions. However, for orphan drugs, country-specific requirements exist. In the Netherlands, orphan drug developers can be exempted from providing a full pharmacoeconomic evaluation,

  2. A review of international coverage and pricing strategies for personalized medicine and orphan drugs.

    Science.gov (United States)

    Degtiar, Irina

    2017-12-01

    Personalized medicine and orphan drugs share many characteristics-both target small patient populations, have uncertainties regarding efficacy and safety at payer submission, and frequently have high prices. Given personalized medicine's rising importance, this review summarizes international coverage and pricing strategies for personalized medicine and orphan drugs as well as their impact on therapy development incentives, payer budgets, and therapy access and utilization. PubMed, Health Policy Reference Center, EconLit, Google Scholar, and references were searched through February 2017 for articles presenting primary data. Sixty-nine articles summarizing 42 countries' strategies were included. Therapy evaluation criteria varied between countries, as did patient cost-share. Payers primarily valued clinical effectiveness; cost was only considered by some. These differences result in inequities in orphan drug access, particularly in smaller and lower-income countries. The uncertain reimbursement process hinders diagnostic testing. Payer surveys identified lack of comparative effectiveness evidence as a chief complaint, while manufacturers sought more clarity on payer evidence requirements. Despite lack of strong evidence, orphan drugs largely receive positive coverage decisions, while personalized medicine diagnostics do not. As more personalized medicine and orphan drugs enter the market, registries can provide better quality evidence on their efficacy and safety. Payers need systematic assessment strategies that are communicated with more transparency. Further studies are necessary to compare the implications of different payer approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Regulatory Forum Review*: Utility of in Vitro Secondary Pharmacology Data to Assess Risk of Drug-induced Valvular Heart Disease in Humans: Regulatory Considerations.

    Science.gov (United States)

    Papoian, Thomas; Jagadeesh, Gowraganahalli; Saulnier, Muriel; Simpson, Natalie; Ravindran, Arippa; Yang, Baichun; Laniyonu, Adebayo A; Khan, Imran; Szarfman, Ana

    2017-04-01

    Drug-induced valvular heart disease (VHD) is a serious side effect linked to long-term treatment with 5-hydroxytryptamine (serotonin) receptor 2B (5-HT 2B ) agonists. Safety assessment for off-target pharmacodynamic activity is a common approach used to screen drugs for this undesired property. Such studies include in vitro assays to determine whether the drug is a 5-HT 2B agonist, a necessary pharmacological property for development of VHD. Measures of in vitro binding affinity (IC 50 , K i ) or cellular functional activity (EC 50 ) are often compared to maximum therapeutic free plasma drug levels ( fC max ) from which safety margins (SMs) can be derived. However, there is no clear consensus on what constitutes an appropriate SM under various therapeutic conditions of use. The strengths and limitations of SM determinations and current risk assessment methodology are reviewed and evaluated. It is concluded that the use of SMs based on K i values, or those relative to serotonin (5-HT), appears to be a better predictor than the use of EC 50 or EC 50 /human fC max values for determining whether known 5-HT 2B agonists have resulted in VHD. It is hoped that such a discussion will improve efforts to reduce this preventable serious drug-induced toxicity from occurring and lead to more informed risk assessment strategies.

  4. Compliance of disease awareness campaigns in printed Dutch media with national and international regulatory guidelines.

    Science.gov (United States)

    Leonardo Alves, Teresa; Martins de Freitas, Auramarina F; van Eijk, Martine E C; Mantel-Teeuwisse, Aukje K

    2014-01-01

    The European legislation prohibits prescription-only medicines' advertising but allows pharmaceutical companies to provide information to the public on health and diseases, provided there is no direct or indirect reference to a pharmaceutical product. Various forms of promotion have become increasingly common in Europe including "disease-oriented" campaigns. To explore examples of disease awareness campaigns by pharmaceutical companies in the Netherlands, by assessing their compliance with the World Health Organization (WHO) Ethical Criteria for medicinal drug promotion and the Dutch guidelines for provision of information by pharmaceutical companies. Materials referring to health/disease and treatments published in the most widely circulated newspapers and magazines were collected from March to May 2012. An evaluation tool was developed based on relevant underlying principles from the WHO ethical criteria and Dutch self-regulation guidelines. Collected disease awareness advertisements were used to pilot the evaluation tool and to explore the consistency of information provided with the WHO and Dutch criteria. Eighty materials met our inclusion criteria; 71 were published in newspapers and 9 in magazines. The large majority were news items but 21 were disease awareness advertisements, of which 5 were duplicates. Fifteen out of the 16 disease awareness campaigns were non-compliant with current guidelines mainly due to lack of balance (n = 12), absence of listed author and/or sponsor (n = 8), use of misleading or incomplete information (n = 5) and use of promotional information (n = 5). None mentioned a pharmaceutical product directly. Disease Awareness Campaigns are present in Dutch printed media. Although no brand names were mentioned, the lack of compliance of disease awareness campaigns with the current regulations is alarming. There were information deficiencies and evidence of information bias. A key concern is that the context in which the information is

  5. Compliance of disease awareness campaigns in printed Dutch media with national and international regulatory guidelines.

    Directory of Open Access Journals (Sweden)

    Teresa Leonardo Alves

    Full Text Available BACKGROUND: The European legislation prohibits prescription-only medicines' advertising but allows pharmaceutical companies to provide information to the public on health and diseases, provided there is no direct or indirect reference to a pharmaceutical product. Various forms of promotion have become increasingly common in Europe including "disease-oriented" campaigns. OBJECTIVES: To explore examples of disease awareness campaigns by pharmaceutical companies in the Netherlands, by assessing their compliance with the World Health Organization (WHO Ethical Criteria for medicinal drug promotion and the Dutch guidelines for provision of information by pharmaceutical companies. METHODS: Materials referring to health/disease and treatments published in the most widely circulated newspapers and magazines were collected from March to May 2012. An evaluation tool was developed based on relevant underlying principles from the WHO ethical criteria and Dutch self-regulation guidelines. Collected disease awareness advertisements were used to pilot the evaluation tool and to explore the consistency of information provided with the WHO and Dutch criteria. FINDINGS: Eighty materials met our inclusion criteria; 71 were published in newspapers and 9 in magazines. The large majority were news items but 21 were disease awareness advertisements, of which 5 were duplicates. Fifteen out of the 16 disease awareness campaigns were non-compliant with current guidelines mainly due to lack of balance (n = 12, absence of listed author and/or sponsor (n = 8, use of misleading or incomplete information (n = 5 and use of promotional information (n = 5. None mentioned a pharmaceutical product directly. CONCLUSION: Disease Awareness Campaigns are present in Dutch printed media. Although no brand names were mentioned, the lack of compliance of disease awareness campaigns with the current regulations is alarming. There were information deficiencies and evidence of information

  6. The NEA International FEP Database and its use in support of regulatory review

    International Nuclear Information System (INIS)

    Sumerling, T.

    1999-01-01

    A working group of the Nuclear Energy Agency has developed a database of features, events and processes (FEPs) relevant to the assessment of the long-term safety of radioactive waste disposal facilities. The Environment Agency participated in this work as described in a previous report, R and D Technical Report P97. This report describes work done in order to (i) provide an electronic version of the NEA International FEP Database in a convenient form suited to the Agency's needs; (ii) determine procedures for use of the Database in support of the Agency's review of an applicant's safety case for solid radioactive disposal, and in other appropriate Agency activities. Section 1 of the report outlines the objectives and work done. Section 2 gives an overview of the current status, development and international use of the NEA FEP Database. Alternative uses of the Database by the Agency, and procedures for use, are discussed in Section 3. Two alternative procedures for use of the Database in scientific and technical review of an applicant's safety case are outlined and compared; these provide a framework for orderly identification and discussion of technical issues within the review. It is concluded that the way in which the Database is used will depend on the circumstances and also the aims and preferences of the Agency. Detailed procedures for the use of the Database are best defined for the specific circumstances, taking account of the level of information available from the applicant, and the time and resources which the Agency may wish to devote to a given phase of review. The NEA FEP Database has been developed as a tool to assist in performing or reviewing safety assessments of radioactive waste disposal facilities. The principle of the Database, and also the software framework, may be equally applicable to other technical or scientific assessments, e.g. of landfill facilities or river catchment pollution studies. Since the Database is now available to the Agency

  7. Polycaprolactone/maltodextrin nanocarrier for intracellular drug delivery: formulation, uptake mechanism, internalization kinetics, and subcellular localization.

    Science.gov (United States)

    Korang-Yeboah, Maxwell; Gorantla, Yamini; Paulos, Simon A; Sharma, Pankaj; Chaudhary, Jaideep; Palaniappan, Ravi

    2015-01-01

    Prostate cancer (PCa) disease progression is associated with significant changes in intracellular and extracellular proteins, intracellular signaling mechanism, and cancer cell phenotype. These changes may have direct impact on the cellular interactions with nanocarriers; hence, there is the need for a much-detailed understanding, as nanocarrier cellular internalization and intracellular sorting mechanism correlate directly with bioavailability and clinical efficacy. In this study, we report the differences in the rate and mechanism of cellular internalization of a biocompatible polycaprolactone (PCL)/maltodextrin (MD) nanocarrier system for intracellular drug delivery in LNCaP, PC3, and DU145 PCa cell lines. PCL/MD nanocarriers were designed and characterized. PCL/MD nanocarriers significantly increased the intracellular concentration of coumarin-6 and fluorescein isothiocyanate-labeled bovine serum albumin, a model hydrophobic and large molecule, respectively. Fluorescence microscopy and flow cytometry analysis revealed rapid internalization of the nanocarrier. The extent of nanocarrier cellular internalization correlated directly with cell line aggressiveness. PCL/MD internalization was highest in PC3 followed by DU145 and LNCaP, respectively. Uptake in all PCa cell lines was metabolically dependent. Extraction of endogenous cholesterol by methyl-β-cyclodextrin reduced uptake by 75%±4.53% in PC3, 64%±6.01% in LNCaP, and 50%±4.50% in DU145, indicating the involvement of endogenous cholesterol in cellular internalization. Internalization of the nanocarrier in LNCaP was mediated mainly by macropinocytosis and clathrin-independent pathways, while internalization in PC3 and DU145 involved clathrin-mediated endocytosis, clathrin-independent pathways, and macropinocytosis. Fluorescence microscopy showed a very diffused and non-compartmentalized subcellular localization of the PCL/MD nanocarriers with possible intranuclear localization and minor colocalization in

  8. Globalization and the uneven application of international regulatory standard : the case of oil exploration in Nigeria

    Energy Technology Data Exchange (ETDEWEB)

    Adalikwu, J.

    2008-07-01

    This study was conducted to increase the awareness of the current economic situation that exists in the Niger Delta, a region that has been devastated by the activities of oil multinational corporations (MNCs). In particular, the study linked the Obelle and Obagi communities to the political economy of global capital which creates inequalities that divide societies into hierarchies of the rich and poor. The strategies adopted by the people to improve the negative consequences of oil exploration in the communities were also examined. The researcher postulated that there is a relationship between the uneven application of international and national regulations in oil production by MNCs and environmental degradation. A critical ethnographic paradigm was used to explore and explain the processes of globalization that affect the people's lives and means of livelihood. Data were collected and analyzed using both qualitative and quantitative methods. Data was then analyzed using several methods, such as statistics based on cross-tabulation, analysis of themes that emerged from interviews, and Atlas.ti 5.0 qualitative analysis computer programme to show the relationship between variables that emerged from the study. The study revealed that resource exploitation by oil MNCs in Obagi/Obelle communities of the Nigeria Delta, together with the Nigerian government, has resulted in economic expropriation, political disenfranchisement, social instability and environmental damage.

  9. Marketing of breast-milk substitutes in Zambia: evaluation of compliance to the international regulatory code.

    Science.gov (United States)

    Funduluka, P; Bosomprah, S; Chilengi, R; Mugode, R H; Bwembya, P A; Mudenda, B

    2018-03-01

    We sought to assess the level of non-compliance with the International Code of Marketing breast-milk substitutes (BMS) and/or Statutory Instrument (SI) Number 48 of 2006 of the Laws of Zambia in two suburbs, Kalingalinga and Chelstone, in Zambia. This was a cross sectional survey. Shop owners (80), health workers (8) and mothers (214) were interviewed. BMS labels and advertisements (62) were observed. The primary outcome was mean non-compliance defined as the number of article violations divided by the total 'obtainable' violations. The score ranges from 0 to 1 with 0 representing no violations in all the articles and one representing violations in all the articles. A total of 62 BMS were assessed. The mean non-compliance score by manufacturers in terms of violations in labelling of BMS was 0.33 (SD = 0.28; 95% CI: 0.26, 0.40). These violations were mainly due to labels containing pictures or graphics representing an infant. 80 shops were also assessed with mean non-compliance score in respect of violations in tie-in-sales, special display, and contact with mothers at the shop estimated as 0.14 (SD = 0.14; 95% CI: 0.11, 0.18). Non-compliance with the Code and/or the local SI is high after 10 years of domesticating the Code.

  10. Use of Fixed Dose Combination (FDC) Drugs in India: Central Regulatory Approval and Sales of FDCs Containing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Metformin, or Psychotropic Drugs

    Science.gov (United States)

    McGettigan, Patricia; Roderick, Peter; Mahajan, Rushikesh; Kadam, Abhay; Pollock, Allyson M.

    2015-01-01

    Background In 2012, an Indian parliamentary committee reported that manufacturing licenses for large numbers of fixed dose combination (FDC) drugs had been issued by state authorities without prior approval of the Central Drugs Standard Control Organization (CDSCO) in violation of rules, and considered that some ambiguity until 1 May 2002 about states’ powers might have contributed. To our knowledge, no systematic enquiry has been undertaken to determine if evidence existed to support these findings. We investigated CDSCO approvals for and availability of oral FDC drugs in four therapeutic areas: analgesia (non-steroidal anti-inflammatory drugs [NSAIDs]), diabetes (metformin), depression/anxiety (anti-depressants/benzodiazepines), and psychosis (anti-psychotics). Methods and Findings This was an ecologic study with a time-trend analysis of FDC sales volumes (2007–2012) and a cross-sectional examination of 2011–2012 data to establish the numbers of formulations on the market with and without a record of CDSCO approval (“approved” and “unapproved”), their branded products, and sales volumes. Data from the CDSCO on approved FDC formulations were compared with sales data from PharmaTrac, a database of national drug sales. We determined the proportions of FDC sales volumes (2011–2012) arising from centrally approved and unapproved formulations and from formulations including drugs banned/restricted internationally. We also determined the proportions of centrally approved and unapproved formulations marketed before and after 1 May 2002, when amendments were made to the drug rules. FDC approvals in India, the United Kingdom (UK), and United States of America (US) were compared. For NSAID FDCs, 124 formulations were marketed, of which 34 (27%) were centrally approved and 90 (73%) were unapproved; metformin: 25 formulations, 20 (80%) approved, five (20%) unapproved; anti-depressants/benzodiazepines: 16 formulations, three (19%) approved, 13 (81%) unapproved

  11. Methods and pitfalls in searching drug safety databases utilising the Medical Dictionary for Regulatory Activities (MedDRA).

    Science.gov (United States)

    Brown, Elliot G

    2003-01-01

    The Medical Dictionary for Regulatory Activities (MedDRA) is a unified standard terminology for recording and reporting adverse drug event data. Its introduction is widely seen as a significant improvement on the previous situation, where a multitude of terminologies of widely varying scope and quality were in use. However, there are some complexities that may cause difficulties, and these will form the focus for this paper. Two methods of searching MedDRA-coded databases are described: searching based on term selection from all of MedDRA and searching based on terms in the safety database. There are several potential traps for the unwary in safety searches. There may be multiple locations of relevant terms within a system organ class (SOC) and lack of recognition of appropriate group terms; the user may think that group terms are more inclusive than is the case. MedDRA may distribute terms relevant to one medical condition across several primary SOCs. If the database supports the MedDRA model, it is possible to perform multiaxial searching: while this may help find terms that might have been missed, it is still necessary to consider the entire contents of the SOCs to find all relevant terms and there are many instances of incomplete secondary linkages. It is important to adjust for multiaxiality if data are presented using primary and secondary locations. Other sources for errors in searching are non-intuitive placement and the selection of terms as preferred terms (PTs) that may not be widely recognised. Some MedDRA rules could also result in errors in data retrieval if the individual is unaware of these: in particular, the lack of multiaxial linkages for the Investigations SOC, Social circumstances SOC and Surgical and medical procedures SOC and the requirement that a PT may only be present under one High Level Term (HLT) and one High Level Group Term (HLGT) within any single SOC. Special Search Categories (collections of PTs assembled from various SOCs by

  12. The role of bioethics in the international prescription drug market: economics and global justice.

    Science.gov (United States)

    Newland, Shelby E

    2006-01-01

    In terms of health care access, bioethics has an important role to inform and shape policy issues and develop interdisciplinary ideas and interventions. The rising price of prescription drugs presents one of the most looming barriers to health care access in the world today. Including both theoretical and practical features of the pharmaceutical industry's behavior is necessary to find ethical solutions towards increasing access. Bioethics can evaluate global justice by weighing human rights theory and future innovation at the macro level, and by addressing market forces and responsibilities at the micro level. Inherent structural features of pharmaceuticals, such as its reliance on research and development, cause the industry to employ pricing strategies that seem counter-intuitive to conventional wisdom, but that result in producing a just allocation as defined by market forces. Parallel trade and drug exportation/reimportation threaten the saliency of the industry's differential pricing scheme; a case-study of a single "Euro-price" within the European Union illustrates how this will actually create harm to the most needy member states. This complex situation requires solutions weighing arguments from human rights theory with those from economic theory to arrive at the most globally just allocation of prescription drugs in the global marketplace, as well as to ensure future innovation and scientific progress. Bioethicists as well as economists need to partake urgently in this discourse for the betterment of the global injustices in the international prescription drug market.

  13. Examining characteristics, knowledge and regulatory practices of specialized drug shops in Sub-Saharan Africa: a systematic review of the literature

    Directory of Open Access Journals (Sweden)

    Wafula Francis N

    2012-07-01

    Full Text Available Abstract Background Specialized drug shops such as pharmacies and drug shops are increasingly becoming important sources of treatment. However, knowledge on their regulatory performance is scarce. We set out to systematically review literature on the characteristics, knowledge and practices of specialized drug shops in Sub-Saharan Africa. Methods We searched PubMed, EMBASE, WEB of Science, CAB Abstracts, PsycINFO and websites for organizations that support medicine policies and usage. We also conducted open searches using Google Scholar, and searched manually through references of retrieved articles. Our search included studies of all designs that described characteristics, knowledge and practices of specialized drug shops. Information was abstracted on authors, publication year, country and location, study design, sample size, outcomes investigated, and primary findings using a uniform checklist. Finally, we conducted a structured narrative synthesis of the main findings. Results We obtained 61 studies, mostly from Eastern Africa, majority of which were conducted between 2006 and 2011. Outcome measures were heterogeneous and included knowledge, characteristics, and dispensing and regulatory practices. Shop location and client demand were found to strongly influence dispensing practices. Whereas shops located in urban and affluent areas were more likely to provide correct treatments, those in rural areas provided credit facilities more readily. However, the latter also charged higher prices for medicines. A vast majority of shops simply sold whatever medicines clients requested, with little history taking and counseling. Most shops also stocked popular medicines at the expense of policy recommended treatments. Treatment policies were poorly communicated overall, which partly explained why staff had poor knowledge on key aspects of treatment such as medicine dosage and side effects. Overall, very little is known on the link between regulatory

  14. Examining characteristics, knowledge and regulatory practices of specialized drug shops in Sub-Saharan Africa: a systematic review of the literature.

    Science.gov (United States)

    Wafula, Francis N; Miriti, Eric M; Goodman, Catherine A

    2012-07-27

    Specialized drug shops such as pharmacies and drug shops are increasingly becoming important sources of treatment. However, knowledge on their regulatory performance is scarce. We set out to systematically review literature on the characteristics, knowledge and practices of specialized drug shops in Sub-Saharan Africa. We searched PubMed, EMBASE, WEB of Science, CAB Abstracts, PsycINFO and websites for organizations that support medicine policies and usage. We also conducted open searches using Google Scholar, and searched manually through references of retrieved articles. Our search included studies of all designs that described characteristics, knowledge and practices of specialized drug shops. Information was abstracted on authors, publication year, country and location, study design, sample size, outcomes investigated, and primary findings using a uniform checklist. Finally, we conducted a structured narrative synthesis of the main findings. We obtained 61 studies, mostly from Eastern Africa, majority of which were conducted between 2006 and 2011. Outcome measures were heterogeneous and included knowledge, characteristics, and dispensing and regulatory practices. Shop location and client demand were found to strongly influence dispensing practices. Whereas shops located in urban and affluent areas were more likely to provide correct treatments, those in rural areas provided credit facilities more readily. However, the latter also charged higher prices for medicines. A vast majority of shops simply sold whatever medicines clients requested, with little history taking and counseling. Most shops also stocked popular medicines at the expense of policy recommended treatments. Treatment policies were poorly communicated overall, which partly explained why staff had poor knowledge on key aspects of treatment such as medicine dosage and side effects. Overall, very little is known on the link between regulatory enforcement and practices of specialized drug shops

  15. Current status of herbal product: Regulatory overview

    Science.gov (United States)

    Sharma, Sanjay

    2015-01-01

    A review of the regulatory status of herbal drugs/products was done for few countries forming part of Asia, Africa, America, Europe, and Australia, to understand various categories under which the trade of herbal products is permitted and their premarketing requirements. A critical assessment was done, to know the hindrances in the process of harmonization of herbal products. It has been found that there is a lack of harmonization in the regulatory requirements of herbal products internationally, besides the issues of availability of herbs and their conservation. These are hindering the international trade and growth of the herbal products segment. PMID:26681886

  16. Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics

    Science.gov (United States)

    Mahmood, M.; Xu, Y.; Dantuluri, V.; Mustafa, T.; Zhang, Y.; Karmakar, A.; Casciano, D.; Ali, S.; Biris, A.

    2013-02-01

    Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells.

  17. Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics

    International Nuclear Information System (INIS)

    Mahmood, M; Xu, Y; Dantuluri, V; Mustafa, T; Karmakar, A; Casciano, D; Biris, A; Zhang, Y; Ali, S

    2013-01-01

    Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells. (paper)

  18. Implementing nuclear non-proliferation in Finland. Regulatory control, international cooperation and the Comprehensive Nuclear-Test-Ban Treaty. Annual report 2011

    Energy Technology Data Exchange (ETDEWEB)

    Okko, O [ed.

    2012-07-01

    The regulatory control of nuclear materials (i.e. nuclear safeguards) is a prerequisite for the peaceful use of nuclear energy in Finland. Safeguards are required for Finland to comply with international agreements on nuclear non-proliferation - mainly the Non-Proliferation Treaty (NPT). This regulatory control is exercised by the Nuclear Materials Section of the Finnish Radiation and Nuclear Safety Authority (STUK). The results of STUK's nuclear safeguards inspection activities in 2011 continued to demonstrate that the Finnish licence holders take good care of their nuclear materials. There were no indications of undeclared nuclear materials or activities and the inspected materials and activities were in accordance with the licence holders' declarations.

  19. Modernizing methodology for the WHO assessment of substances for the international drug control conventions.

    Science.gov (United States)

    Danenberg, E; Sorge, L A; Wieniawski, W; Elliott, S; Amato, L; Scholten, W K

    2013-08-01

    The WHO Executive Board revised the guidance that governs the procedures for the WHO review of psychoactive substances for international drug control in 2010. To meet the standards defined in these guidelines, the current evaluation methodology at WHO must be an evidence-based assessment. We describe the history of substance evaluation from 1912 to the present and the development of the evaluation methods over time including a description of the current assessment system, using reports from WHO and its predecessor, the League of Nations. Furthermore, we describe the current review system. We found that some substances under international control were never reviewed; other substances were reviewed decades ago. We argue that assessments do not have unlimited validity, and therefore, substances need to be re-assessed periodically, as already recommended by the Expert Committee on Drug Dependence in 1982. We propose that the evaluation time be shortened; that the influence of the route of administration and/or dosage form of the preparation is considered in the evaluation; and we recommend studying national and regional assessment systems and adopting their best practices. With this article, we make a case for the inclusion of systematic review and other methods of comprehensive analysis of substance evaluation to arrive at a process of equal rigour and quality as already applied by WHO for the development of treatment guidelines. Copyright © 2013 World Health Organization. Published by Elsevier Ireland Ltd.. All rights reserved.

  20. Oseltamivir prescription and regulatory actions vis-à-vis abnormal behavior risk in Japan: drug utilization study using a nationwide pharmacy database.

    Science.gov (United States)

    Urushihara, Hisashi; Doi, Yuko; Arai, Masaru; Matsunaga, Toshiyuki; Fujii, Yosuke; Iino, Naoko; Kawamura, Takashi; Kawakami, Koji

    2011-01-01

    In March 2007, a regulatory advisory was issued in Japan to restrict oseltamivir use in children aged 10-19 years because of safety concerns over abnormal behavior. The effectiveness and validity of regulatory risk minimization actions remain to be reviewed, despite their significant public health implications. To assess the impact of the regulatory actions on prescribing practices and safety reporting. METHODOLOY/PRINICPAL FINDINGS: In this retrospective review of a nationwide pharmacy database, we analyzed 100,344 dispensation records for oseltamivir and zanamivir for the period from November 2006 to March 2009. The time trend in dispensations for these antiviral agents was presented before and after the regulatory actions, contrasted with intensity of media coverage and the numbers of spontaneous adverse reaction reports with regard to antivirals. The 2007 regulatory actions, together with its intense media coverage, reduced oseltamivir dispensation in targeted patients in fiscal year 2008 to 20.4% of that in fiscal year 2006, although influenza activities were comparable between these fiscal years. In contrast, zanamivir dispensation increased approximately nine-fold across all age groups. The number of abnormal behavior reports associated with oseltamivir in children aged 10-19 years decreased from fiscal year 2006 to 2008 (24 to 9 cases); this decline was offset by the increased number of reports of abnormal behavior in children under age 10 (12 to 28 cases). The number of reports associated with zanamivir increased in proportion to increased dispensation of this drug (11 to 114 cases). The 2007 actions effectively reduced oseltamivir prescriptions and the number of reports of abnormal behavior in the targeted group. The observed increase in abnormal behavior reports in oseltamivir patients under age 10 and in zanamivir patients suggests that these patient groups may also be at risk, calling into question the validity of the current discrimination by age and

  1. Oseltamivir prescription and regulatory actions vis-à-vis abnormal behavior risk in Japan: drug utilization study using a nationwide pharmacy database.

    Directory of Open Access Journals (Sweden)

    Hisashi Urushihara

    Full Text Available BACKGROUND: In March 2007, a regulatory advisory was issued in Japan to restrict oseltamivir use in children aged 10-19 years because of safety concerns over abnormal behavior. The effectiveness and validity of regulatory risk minimization actions remain to be reviewed, despite their significant public health implications. To assess the impact of the regulatory actions on prescribing practices and safety reporting. METHODOLOY/PRINICPAL FINDINGS: In this retrospective review of a nationwide pharmacy database, we analyzed 100,344 dispensation records for oseltamivir and zanamivir for the period from November 2006 to March 2009. The time trend in dispensations for these antiviral agents was presented before and after the regulatory actions, contrasted with intensity of media coverage and the numbers of spontaneous adverse reaction reports with regard to antivirals. The 2007 regulatory actions, together with its intense media coverage, reduced oseltamivir dispensation in targeted patients in fiscal year 2008 to 20.4% of that in fiscal year 2006, although influenza activities were comparable between these fiscal years. In contrast, zanamivir dispensation increased approximately nine-fold across all age groups. The number of abnormal behavior reports associated with oseltamivir in children aged 10-19 years decreased from fiscal year 2006 to 2008 (24 to 9 cases; this decline was offset by the increased number of reports of abnormal behavior in children under age 10 (12 to 28 cases. The number of reports associated with zanamivir increased in proportion to increased dispensation of this drug (11 to 114 cases. CONCLUSIONS/SIGNIFICANCE: The 2007 actions effectively reduced oseltamivir prescriptions and the number of reports of abnormal behavior in the targeted group. The observed increase in abnormal behavior reports in oseltamivir patients under age 10 and in zanamivir patients suggests that these patient groups may also be at risk, calling into question

  2. A Transcriptional Regulatory Network Containing Nuclear Receptors and Long Noncoding RNAs Controls Basal and Drug-Induced Expression of Cytochrome P450s in HepaRG Cells.

    Science.gov (United States)

    Chen, Liming; Bao, Yifan; Piekos, Stephanie C; Zhu, Kexin; Zhang, Lirong; Zhong, Xiao-Bo

    2018-07-01

    Cytochrome P450 (P450) enzymes are responsible for metabolizing drugs. Expression of P450s can directly affect drug metabolism, resulting in various outcomes in therapeutic efficacy and adverse effects. Several nuclear receptors are transcription factors that can regulate expression of P450s at both basal and drug-induced levels. Some long noncoding RNAs (lncRNAs) near a transcription factor are found to participate in the regulatory functions of the transcription factors. The aim of this study is to determine whether there is a transcriptional regulatory network containing nuclear receptors and lncRNAs controlling both basal and drug-induced expression of P450s in HepaRG cells. Small interfering RNAs or small hairpin RNAs were applied to knock down four nuclear receptors [hepatocyte nuclear factor 1 α (HNF1 α ), hepatocyte nuclear factor 4 α (HNF4 α ), pregnane X receptor (PXR), and constitutive androstane receptor (CAR)] as well as two lncRNAs [HNF1 α antisense RNA 1 (HNF1 α -AS1) and HNF4 α antisense RNA 1 (HNF4 α -AS1)] in HepaRG cells with or without treatment of phenobarbital or rifampicin. Expression of eight P450 enzymes was examined in both basal and drug-induced levels. CAR and PXR mainly regulated expression of specific P450s. HNF1 α and HNF4 α affected expression of a wide range of P450s as well as other transcription factors. HNF1 α and HNF4 α controlled the expression of their neighborhood lncRNAs, HNF1 α -AS1 and HNF4 α -AS1, respectively. HNF1 α -AS1 and HNF4 α -AS1 was also involved in the regulation of P450s and transcription factors in diverse manners. Altogether, our study concludes that a transcription regulatory network containing the nuclear receptors and lncRNAs controls both basal and drug-induced expression of P450s in HepaRG cells. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Regulatory activities; Actividades regulatorias

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information.

  4. 76 FR 19373 - The 14th Annual Food and Drug Administration-Orange County Regulatory Affairs Educational...

    Science.gov (United States)

    2011-04-07

    ... Orange County Regulatory Affairs Discussion Group, Attention to Detail, 5319 University Dr., suite 641... verified the Web site address, but FDA is not responsible for any subsequent changes to the Web site after.../ Students.* After May 1, 2011, $725.00 for members, $775.00 for non- members, and $475.00 for FDA/Government...

  5. Drug Pricing Reforms

    DEFF Research Database (Denmark)

    Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas

    2015-01-01

    Reference price systems for prescription drugs have found widespread use as cost containment tools. Under such regulatory regimes, patients co-pay a fraction of the difference between pharmacy retail price of the drug and a reference price. Reference prices are either externally (based on drug...... prices in other countries) or internally (based on domestic drug prices) determined. In a recent study, we analysed the effects of a change from external to internal reference pricing in Denmark in 2005, finding that the reform led to substantial reductions in prices, producer revenues, and expenditures...... for patients and the health insurance system. We also estimated an increase in consumer welfare but the size effect depends on whether or not perceived quality differences between branded and other drugs are taken into account....

  6. Application of international recommendations and guidance on low level radioactive waste management and remediation of contaminated land at the national level: Experience of regulatory support in Northwest Russia

    International Nuclear Information System (INIS)

    Sneve, M.; Smith, G.M.; Kerrigan, E

    2005-01-01

    This paper notes the developments in international recommendations on radioactive waste management and remediation of contaminated land and considers their implementation in the context of the Norwegian Plan of Action to improve nuclear safety in North West Russia. Summary information is provided on projects to implement waste management activities (so-called Industrial Projects) and on projects to support regulatory supervision of waste management activities (so-called Regulatory Support Projects). The links between international recommendations and national practice are discussed and it is concluded that, in practice, the details of national standards differ both among themselves and, in some respects, from the recommendations of the ICRP and IAEA. Examples of further potential collaboration projects are listed. While separate responsibilities among organisations have to clear and maintained, combined involvement of operators and regulators is recognised as a prioritised area in future cooperation between NRPA and Russia. (author)

  7. Experience with Regulatory Strategies in Nuclear Power Oversight. Part 1: An International Exploratory Study. Part 2: Workshop Discussions and Conclusions

    Energy Technology Data Exchange (ETDEWEB)

    Melber, Barbara [Melber Consulting, Seattle, WA (United States); Durbin, Nancy E. [Nancy E. Durbin Consulting, Kirkland, WA (United States); Tael, Irene (ed.) [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

    2005-03-01

    This report presents the results of a study which explored the use of six different regulatory strategies for oversight of commercial nuclear power facilities: prescriptive, case-based, outcome-based, risk-based, process-based, and self-assessment strategies. Information was collected on experiences with the use of these different regulatory strategies from experts from nuclear regulatory agencies in Canada, Finland, Spain, Sweden, the United Kingdom and the United States. Systematic, structured open-ended interviews with expert regulators with extensive experience were used in order to understand how regulatory strategies are applied in practice. Common patterns were identified regarding: Experts' perspectives on the major benefits and difficulties of using specific regulatory strategies; Experts' experiences with using regulatory strategies for three areas of oversight-design and modifications, quality systems, and training and qualifications; Expert views of the consequences of different regulatory strategies; Issues that emerged in the interviews regarding regulatory strategies. The major benefit of a prescriptive strategy was that it is clear about requirements and expectations. The major difficulties were that it takes responsibility away from the licensee, it requires a high use of regulator resources and is rigid and difficult to change. A case-based strategy had the key benefit of flexibility for adapting regulatory responses to unique situations, but the difficulties of being considered arbitrary, inconsistent, and unfair and requiring heavy resource use. An outcome-based strategy had the main benefit of allowing licensees to decide the best way to operate m order to meet safety goals, but the major difficulty of identifying appropriate ways to measure safety performance. The major benefit of a risk strategy was its use co prioritize safety issues and allocate resources. However, it was considered inappropriate to use as a stand alone strategy

  8. Experience with Regulatory Strategies in Nuclear Power Oversight. Part 1: An International Exploratory Study. Part 2: Workshop Discussions and Conclusions

    International Nuclear Information System (INIS)

    Melber, Barbara; Durbin, Nancy E.; Tael, Irene

    2005-03-01

    This report presents the results of a study which explored the use of six different regulatory strategies for oversight of commercial nuclear power facilities: prescriptive, case-based, outcome-based, risk-based, process-based, and self-assessment strategies. Information was collected on experiences with the use of these different regulatory strategies from experts from nuclear regulatory agencies in Canada, Finland, Spain, Sweden, the United Kingdom and the United States. Systematic, structured open-ended interviews with expert regulators with extensive experience were used in order to understand how regulatory strategies are applied in practice. Common patterns were identified regarding: Experts' perspectives on the major benefits and difficulties of using specific regulatory strategies; Experts' experiences with using regulatory strategies for three areas of oversight-design and modifications, quality systems, and training and qualifications; Expert views of the consequences of different regulatory strategies; Issues that emerged in the interviews regarding regulatory strategies. The major benefit of a prescriptive strategy was that it is clear about requirements and expectations. The major difficulties were that it takes responsibility away from the licensee, it requires a high use of regulator resources and is rigid and difficult to change. A case-based strategy had the key benefit of flexibility for adapting regulatory responses to unique situations, but the difficulties of being considered arbitrary, inconsistent, and unfair and requiring heavy resource use. An outcome-based strategy had the main benefit of allowing licensees to decide the best way to operate m order to meet safety goals, but the major difficulty of identifying appropriate ways to measure safety performance. The major benefit of a risk strategy was its use co prioritize safety issues and allocate resources. However, it was considered inappropriate to use as a stand alone strategy and a

  9. A Decade in the MIST: Learnings from Investigations of Drug Metabolites in Drug Development under the "Metabolites in Safety Testing" Regulatory Guidance.

    Science.gov (United States)

    Schadt, Simone; Bister, Bojan; Chowdhury, Swapan K; Funk, Christoph; Hop, Cornelis E C A; Humphreys, W Griffith; Igarashi, Fumihiko; James, Alexander D; Kagan, Mark; Khojasteh, S Cyrus; Nedderman, Angus N R; Prakash, Chandra; Runge, Frank; Scheible, Holger; Spracklin, Douglas K; Swart, Piet; Tse, Susanna; Yuan, Josh; Obach, R Scott

    2018-06-01

    Since the introduction of metabolites in safety testing (MIST) guidance by the Food and Drug Administration in 2008, major changes have occurred in the experimental methods for the identification and quantification of metabolites, ways to evaluate coverage of metabolites, and the timing of critical clinical and nonclinical studies to generate this information. In this cross-industry review, we discuss how the increased focus on human drug metabolites and their potential contribution to safety and drug-drug interactions has influenced the approaches taken by industry for the identification and quantitation of human drug metabolites. Before the MIST guidance was issued, the method of choice for generating comprehensive metabolite profile was radio chromatography. The MIST guidance increased the focus on human drug metabolites and their potential contribution to safety and drug-drug interactions and led to changes in the practices of drug metabolism scientists. In addition, the guidance suggested that human metabolism studies should also be accelerated, which has led to more frequent determination of human metabolite profiles from multiple ascending-dose clinical studies. Generating a comprehensive and quantitative profile of human metabolites has become a more urgent task. Together with technological advances, these events have led to a general shift of focus toward earlier human metabolism studies using high-resolution mass spectrometry and to a reduction in animal radiolabel absorption/distribution/metabolism/excretion studies. The changes induced by the MIST guidance are highlighted by six case studies included herein, reflecting different stages of implementation of the MIST guidance within the pharmaceutical industry. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  10. Acute bacterial skin and skin structure infections in internal medicine wards: old and new drugs.

    Science.gov (United States)

    Falcone, Marco; Concia, Ercole; Giusti, Massimo; Mazzone, Antonino; Santini, Claudio; Stefani, Stefania; Violi, Francesco

    2016-08-01

    Skin and soft tissue infections (SSTIs) are a common cause of hospital admission among elderly patients, and traditionally have been divided into complicated and uncomplicated SSTIs. In 2010, the FDA provided a new classification of these infections, and a new category of disease, named acute bacterial skin and skin structure infections (ABSSSIs), has been proposed as an independent clinical entity. ABSSSIs include three entities: cellulitis and erysipelas, wound infections, and major cutaneous abscesses This paper revises the epidemiology of SSTIs and ABSSSIs with regard to etiologies, diagnostic techniques, and clinical presentation in the hospital settings. Particular attention is owed to frail patients with multiple comorbidities and underlying significant disease states, hospitalized on internal medicine wards or residing in nursing homes, who appear to be at increased risk of infection due to multi-drug resistant pathogens and treatment failures. Management of ABSSSIs and SSTIs, including evaluation of the hemodynamic state, surgical intervention and treatment with appropriate antibiotic therapy are extensively discussed.

  11. Proyecto Grannacional ALBASALUD para Centro Regulador de Medicamentos Esenciales de los países del ALBA-TCP Grand-national Project ALBASALUD for Regulatory Center of Essential Drugs for the ALBA-TCP countries

    Directory of Open Access Journals (Sweden)

    Celeste Aurora Sánchez González

    2011-09-01

    countries. It will provide a Grand-national Register that will be valid for all the member states to facilitate the access to quality essential drugs. The objective of this research work was to design and to conduct a project from the technical viewpoint in order to lay down the legal and methodological basis of the future center and its main functions. Some techniques like nominal group, points of reference and expert consultation were used, and the specific methodologies to plan and to prepare the required documents were devised. The guidelines of international regulatory bodies, the basic groups of drugs and the pharmaceutical regulations of the participating countries were reviewed. Several documents and strategies for the project work in the pre-investment stage were developed, the first listing of essential drugs for the ALBA countries was defined and the main legal provisions and the regulation that states the functions of registering, surveillance, supervision, lab work and release of batches of the new entity were approved. The Grand-national Project ALBASALUD " Regulatory Center of Drugs for the ALBA-TCP" has proved its efficiency and capacities to achieve the set objectives through collective involvement-supported scientific and technical work that has guaranteed the required provisions and guidelines for the basic functions and the legal endorsement of the center.

  12. Regulating khat--dilemmas and opportunities for the international drug control system.

    Science.gov (United States)

    Klein, Axel; Beckerleg, Susan; Hailu, Degol

    2009-11-01

    The regulation of khat, one of the most recent psychoactive drugs to become a globally traded commodity, remains hotly contested within different producer and consumer countries. As regimes vary, it has been possible to compare khat policies in Africa, Europe and North America from different disciplinary perspectives. Field research was conducted in East Africa and Europe, using a combination of semistructured interviews, participant observation and the analysis of trade statistics. The research established the significance of khat for rural producers, regional economies, as a tax base and source of foreign exchange. At the same time, khat as a psychoactive substance is associated with health and public safety problems that in turn are met with often ill-informed legislative responses. Bans have in turn lead to the criminalisation of users and sellers and illegal drug markets. The empirical work from Africa provides a strong argument for promoting evidence-based approaches to khat regulation, harnessing the positive aspects of the khat economy to develop a control model that incorporates the voices and respects the needs of rural producers. Ultimately, the framework for khat may provide both a model and an opportunity for revising the international treaties governing the control of other plant psychoactive-based substances.

  13. Charomers-Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery.

    Science.gov (United States)

    Hahn, Ulrich

    2017-12-06

    Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2'-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers-in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

  14. Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery

    Science.gov (United States)

    2017-01-01

    Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld. PMID:29211023

  15. Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ulrich Hahn

    2017-12-01

    Full Text Available Interleukin-6 (IL-6 is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT. Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

  16. Patient-Reported Outcomes in Cancer Drug Development and US Regulatory Review: Perspectives From Industry, the Food and Drug Administration, and the Patient.

    Science.gov (United States)

    Basch, Ethan; Geoghegan, Cindy; Coons, Stephen Joel; Gnanasakthy, Ari; Slagle, Ashley F; Papadopoulos, Elektra J; Kluetz, Paul G

    2015-06-01

    Data reported directly by patients about how they feel and function are rarely included in oncology drug labeling in the United States, in contrast to Europe and to nononcology labeling in the United States, where this practice is more common. Multiple barriers exist, including challenges unique to oncology trials, and industry's concerns regarding cost, logistical complexities, and the Food and Drug Administration's (FDA's) rigorous application of its 2009 guidance on the use of patient-reported outcome (PRO) measures. A panel consisting of representatives of industry, FDA, the PRO Consortium, clinicians, and patients was assembled at a 2014 workshop cosponsored by FDA to identify practical recommendations for overcoming these barriers. Key recommendations included increasing proactive encouragement by FDA to clinical trial sponsors for including PROs in drug development programs; provision of comprehensive PRO plans by sponsors to FDA early in drug development; promotion of an oncology-specific PRO research agenda; development of an approach to existing ("legacy") PRO measures, when appropriate (focused initially on symptoms and functional status); and increased FDA and industry training in PRO methodology. FDA has begun implementing several of these recommendations.

  17. Illicit drugs policy through the lens of regulation.

    Science.gov (United States)

    Ritter, Alison

    2010-07-01

    The application of regulatory theory to the problem of illicit drugs has generally been thought about only in terms of 'command and control'. The international treaties governing global illicit drug control and the use of law enforcement to dissuade and punish offenders have been primary strategies. In this paper I explore the application of other aspects of regulatory theory to illicit drugs-primarily self-regulation and market regulation. There has been an overreliance on strategies from the top of the regulatory pyramid. Two other regulatory strategies--self-regulation and market regulation--can be applied to illicit drugs. Self-regulation, driven by the proactive support of consumer groups may reduce drug-related harms. Market strategies such as pill-testing can change consumer preferences and encourage alternate seller behaviour. Regulatory theory is also concerned with partnerships between the state and third parties: strategies in these areas include partnerships between police and pharmacies regarding sale of potential precursor chemicals. Regulatory theory and practice is a rich and well-developed field in the social sciences. I argue that governments should consider the full array of regulatory strategies. Using regulatory theory provides a rationale and justification to strategies that are currently at the whim of politics, such as funding for user groups. The greater application of regulatory approaches may produce more flexible and structured illicit drug policies. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  18. Drug-related problems identification in general internal medicine: The impact and role of the clinical pharmacist and pharmacologist.

    Science.gov (United States)

    Guignard, Bertrand; Bonnabry, Pascal; Perrier, Arnaud; Dayer, Pierre; Desmeules, Jules; Samer, Caroline Flora

    2015-07-01

    Patients admitted to general internal medicine wards might receive a large number of drugs and be at risk for drug-related problems (DRPs) associated with increased morbidity and mortality. This study aimed to detect suboptimal drug use in internal medicine by a pharmacotherapy evaluation, to suggest treatment optimizations and to assess the acceptance and satisfaction of the prescribers. This was a 6-month prospective study conducted in two internal medicine wards. Physician rounds were attended by a pharmacist and a pharmacologist. An assessment grid was used to detect the DRPs in electronic prescriptions 24h in advance. One of the following interventions was selected, depending on the relevance and complexity of the DRPs: no intervention, verbal advice of treatment optimization, or written consultation. The acceptance rate and satisfaction of prescribers were measured. In total, 145 patients were included, and 383 DRPs were identified (mean: 2.6 DRPs per patient). The most frequent DRPs were drug interactions (21%), untreated indications (18%), overdosages (16%) and drugs used without a valid indication (10%). The drugs or drug classes most frequently involved were tramadol, antidepressants, acenocoumarol, calcium-vitamin D, statins, aspirin, proton pump inhibitors and paracetamol. The following interventions were selected: no intervention (51%), verbal advice of treatment optimization (42%), and written consultation (7%). The acceptance rate of prescribers was 84% and their satisfaction was high. Pharmacotherapy expertise during medical rounds was useful and well accepted by prescribers. Because of the modest allocation of pharmacists and pharmacologists in Swiss hospitals, complementary strategies would be required. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  19. Learning from nuclear regulatory self-assessment. International peer review of the CSN report on lessons learnt from the essential service water system degradation event at the Vandellos nuclear power plant

    International Nuclear Information System (INIS)

    2006-01-01

    Nuclear regulatory self-assessment together with the benchmarking of regulatory practices against those of other countries operating nuclear power plants are key elements in maintaining a high level of nuclear safety. In that light, the Spanish Consejo de Seguridad Nuclear (CSN) formally asked the OECD Nuclear Energy Agency (NEA) to establish an international peer review team to assess the CSN report on the lessons learnt as a result of the 2004 Vandellos II event involving essential service water system degradation. The International Review Team considers the CSN report prepared in follow-up to the Vandellos event to be a commendable effort in regulatory self-assessment. The report, complemented by this international peer review, should enable the CSN to take appropriate action to ensure that its regulatory supervision is in line with best international practice. (authors)

  20. Protecting the public or setting the bar too high? Understanding the causes and consequences of regulatory actions of front-line regulators and specialized drug shop operators in Kenya.

    Science.gov (United States)

    Wafula, Francis; Molyneux, Catherine; Mackintosh, Maureen; Goodman, Catherine

    2013-11-01

    The problem of poor regulatory compliance has been widely reported across private health providers in developing countries. Less known are the underlying reasons for poor compliance, especially with regards to the roles played by front-line regulatory staff, and the regulatory institution as a whole. We designed a qualitative study to address this gap, with the study questions and tools drawing on a conceptual framework informed by theoretical literature on regulation. Data were collected from specialized drug shops (SDSs) in two rural districts in Western Kenya in 2011 through eight focus group discussions, and from regulatory staff from organizations governing the pharmaceutical sector through a total of 24 in-depth interviews. We found that relationships between front-line regulators and SDS operators were a strong influence on regulatory behaviour, often resulting in non-compliance and perverse outcomes such as corruption. It emerged that separate regulatory streams operated in urban and rural locations, based mainly on differing relationships between the front-line regulators and SDS operators, and on broader factors such as the competition environment and community expectations. Effective incentive structures for regulatory staff were either absent, or poorly linked to performance in regulatory organizations, resulting in divergences between the purposes of the regulatory organization and activities of front-line staff. Given the rural-urban differences in the practice environment, the introduction of lower retail practice requirements for rural SDSs could be considered. This would allow illegally operated shops to be brought within the regulatory framework, facilitating good quality provision of essential commodities to marginalized areas, without lowering the practice requirements for the better complying urban SDSs. In addition, regulatory organizations need to devise incentives that better link the level of effort to rewards such as professional

  1. Implementing nuclear non-proliferation in Finland. Regulatory control, international cooperation and the Comprehensive Nuclear-Test-Ban Treaty. Annual report 2011

    Energy Technology Data Exchange (ETDEWEB)

    Okko, O. (ed.)

    2012-07-01

    The regulatory control of nuclear materials (i.e. nuclear safeguards) is a prerequisite for the peaceful use of nuclear energy in Finland. Safeguards are required for Finland to comply with international agreements on nuclear non-proliferation - mainly the Non-Proliferation Treaty (NPT). This regulatory control is exercised by the Nuclear Materials Section of the Finnish Radiation and Nuclear Safety Authority (STUK). The results of STUK's nuclear safeguards inspection activities in 2011 continued to demonstrate that the Finnish licence holders take good care of their nuclear materials. There were no indications of undeclared nuclear materials or activities and the inspected materials and activities were in accordance with the licence holders' declarations.

  2. International safety standards and regulatory practices and their application to Brazilian nuclear power plants - a realistic view

    International Nuclear Information System (INIS)

    Almeida, Claudio; Camargo, Claudio

    1999-01-01

    An international nuclear safety regime is being established through a series of binding safety conventions, voluntarily adopted international safety standards and an accompanying peer review process. The basis for the evaluation of each country performance within this international regime should be the international practices. However, local conditions should be taken into account to avoid undue stress of the limited resources available to countries with a limited nuclear power programme. This work reviews the current international nuclear safety and discusses the application of some international practices to the Brazilian situation, considering the peculiarities of the national nuclear power programme and the limitations of the available financial and human resources. (author)

  3. Prevalence of potential drug–drug interactions among internal medicine ward in University of Gondar Teaching Hospital, Ethiopia

    Directory of Open Access Journals (Sweden)

    Akshaya Srikanth Bhagavathula

    2014-05-01

    Conclusion: We have recorded a high rate of prevalence of potential DDI in the internal medicine ward of UOG hospital and a high number of clinically significant DDIs which the most prevalent DDI were of moderate severity. Careful selection of drugs and active pharmaceutical care is encouraged in order to avoid negative consequences of these interactions.

  4. An Assessment of the Efficiency of Government Regulatory Agencies in Nigeria. Case of the National Agency for Food and Drugs Administration and Control

    Directory of Open Access Journals (Sweden)

    Aiwanehi Barbara Ofuani

    2015-09-01

    Full Text Available This study examines Business, Government and Society interrelationships. It eventually narrowed down to assessing the efficiency of government regulatory agencies, in fulfilling the role of government in protecting consumers from unscrupulous practices of businesses. The National Agency for Food and Drugs Administration and Control (NAFDAC was chosen for the study. Since the expectations of the consumers are paramount here, the stakeholder approach method was used for assessing the efficiency of NAFDAC. Literature and previous empirical studies on the topic were examined. For representativeness, data was collected utilizing the survey research design through Questionnaire distributed to 200 respondents in some areas of Lagos Mainland in Lagos state, using the convenience sampling method. 187 copies of the questionnaire representing 93.5% were returned and usable. Descriptive statistics was used to analyze the responses to questions regarding the efficiency of NAFDAC and a hypothesis tested using a one-sample T-test. The findings ran contrary to results from some previous studies. Instead, consumer awareness of the existence of NAFDAC as a regulatory agency and its functions were established, along with a high rate of consumer education. The assessment of its efficiency also showed a high rating. Recommendations were made that the study be replicated in other states of Nigeria and further studies carried out to evaluate its efficiency under previous and current directors for improvement purposes.

  5. Report on the 10th anniversary of international drug discovery science and technology conference, 8 - 10 november 2012, nanjing, china.

    Science.gov (United States)

    Everett, Jeremy R

    2013-03-01

    The 10th Anniversary of International Drug Discovery Science and Technology (IDDST) Conference was held in Nanjing, China from 8 to 10 November 2012. The conference ran in parallel with the 2nd Annual Symposium of Drug Delivery Systems. Over 400 delegates from both conferences came together for the Opening Ceremony and Keynote Addresses but otherwise pursued separate paths in the huge facilities of the Nanjing International Expo Centre. The IDDST was arranged into 19 separate Chapters covering drug discovery biology, target validation, chemistry, rational drug design, pharmacology and toxicology, drug screening technology, 'omics' technologies, analytical, automation and enabling technologies, informatics, stem cells and regenerative medicine, bioprocessing, generics, biosimilars and biologicals and seven disease areas: cancer, CNS, respiratory and inflammation, autoimmune, emerging infectious, bone and orphan diseases. There were also two sessions of a 'Bench to Bedside to Business' Program and a Chinese Scientist programme. In each period of the IDDST conference, up to seven sessions were running in parallel. This Meeting Highlight samples just a fraction of the content of this large meeting. The talks included have as a link, the use of new approaches to drug discovery. Many other excellent talks could have been highlighted and the author has necessarily had to be selective.

  6. 76 FR 49773 - International Conference on Harmonisation; Guidance on E16 Biomarkers Related to Drug or...

    Science.gov (United States)

    2011-08-11

    ... sponsors are the European Commission; the European Federation of Pharmaceutical Industries Associations... Pharmaceutical Research and Manufacturers of America. The ICH Secretariat, which coordinates the preparation of..., many important initiatives have been undertaken by regulatory authorities and industry associations to...

  7. Use of controlled internal drug releasing (CIDR) devices to control reproduction in goats: A review.

    Science.gov (United States)

    Knights, Marlon; Singh-Knights, Doolarie

    2016-09-01

    High reproductive rates are necessary in order to increase the productivity of goat operations. Progesterone and its analogues are widely used in other species to control the reproductive system to facilitate synchronized births, induce fertile estrus or to facilitate the use of assisted reproductive techniques with the goal of increasing productivity of livestock. Progesterone impregnated controlled internal drug releasing (CIDR) devices are approved for delivery of the natural hormone progesterone to synchronize and induce fertile estrus in sheep. A few studies have reported a high estrous response and pregnancy rates when CIDRs are used to induce estrus in goats. However, significant variation exists in the duration of treatment (5-16 days) and in the use of exogenous gonadotropins as part of the treatment protocol. As gonadotropins are not currently approved for commercial use in small ruminants in the USA, studies are needed to determine the necessity for exogenous gonadotropins and whether they can be replaced by enhancing endogenous secretion through photoperiodic manipulation of the doe and \\ or increase stimulation through the 'buck-effect'. Future studies must not only evaluate efficacy, but should consider the economic feasibility of using CIDRs in commercial production systems. © 2016 Japanese Society of Animal Science.

  8. Reform by subtraction: the path of denunciation of international drug treaties and reaccession with reservations.

    Science.gov (United States)

    Room, Robin

    2012-09-01

    Almost all countries are parties to the international drug conventions of 1961, 1971 and 1988. These strongly bind parties with respect to their domestic regulation of controlled substances, including requirements that possession, growing or use be a criminal offense and that any regulated market in the substances be limited to use only for medical or scientific purposes. Even where countries have argued they have "wiggle room", reform within the bounds of the conventions has often resulted in "net-widening" which nullifies the intent of the reform. Among the options for effective reform, probably the most immediately viable is the route of denunciation and reaccession with reservations--the route which Bolivia has now taken in order to legalise a regulated domestic market in coca leaves for chewing. The paper considers the existing record of reservations (by more than 30 parties to each of the conventions). Also discussed are the options for response to the reservations by other parties, which vary between the treaties, and how pursuing the option of denunciation and reaccession with reservation might potentially play out. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Structural equation modeling of the effects of racism, LGBTQ discrimination, and internalized oppression on illicit drug use in LGBTQ people of color.

    Science.gov (United States)

    Drazdowski, Tess K; Perrin, Paul B; Trujillo, Michael; Sutter, Megan; Benotsch, Eric G; Snipes, Daniel J

    2016-02-01

    Experiences with lesbian, gay, bisexual, transgender, or queer (LGBTQ) discrimination and racism have both been associated with mental health problems and illicit drug use. However, the cumulative effects of both forms of discrimination--and resulting internalized oppression--on illicit drug use in LGBTQ people of color (POC) has not been examined in the research literature. Using online questionnaires, this study collected self-report data from 200 LGBTQ POC about their experiences with racism, LGBTQ discrimination, internalized racism, internalized LGBTQ discrimination, and illicit drug use. Two structural equation models yielded adequate fit indices in which experiences with racism and LGBTQ discrimination led to more internalized oppression, which then led to greater illicit drug use magnitude. LGBTQ discrimination was directly related to increased internalized oppression, which was positively associated with illicit drug use magnitude; the relationship between LGBTQ discrimination and illicit drug use magnitude was mediated by internalized oppression in both models. However, racism and the interaction between racism and LGBTQ discrimination did not show valid direct effects on internalized oppression or indirect effects on illicit drug use magnitude. LGBTQ POC can be the targets of both racism and LGBTQ discrimination, although the current study found that the most psychologically damaging effects may come from LGBTQ discrimination. Interventions meant to decrease or prevent illicit drug use in LGBTQ POC may benefit from helping participants examine the links among LGBTQ discrimination, internalized oppression, and illicit drug use as a coping strategy, focusing on substituting more adaptive coping. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. 76 FR 28046 - Memorandum of Understanding Between the Food and Drug Administration and the International...

    Science.gov (United States)

    2011-05-13

    ... Tots Public-Private Partnership AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0005; FDA 225-09-0014] Memorandum of Understanding Between the Food and Drug Administration and the...

  11. International certification of nuclear power reactors design. A proposal from the U.S. NRC (Nuclear Regulatory Commission)

    International Nuclear Information System (INIS)

    Felizia, Eduardo R.

    2006-01-01

    The proposal foundations of the Nuclear Regulatory Commission Board Chairman are briefly described, which were enunciated at a meeting on Fourth Generation Reactors (Washington, March 2005). This proposal is analyzed mainly from the point of view of its consequences in third countries buyers of nuclear technology. The analysis is complemented by descriptions of the current process of the NRC design certification and of Third and Fourth Generation Reactors. (author) [es

  12. A high efficiency, high quality and low cost internal regulated bioanalytical laboratory to support drug development needs.

    Science.gov (United States)

    Song, Yan; Dhodda, Raj; Zhang, Jun; Sydor, Jens

    2014-05-01

    In the recent past, we have seen an increase in the outsourcing of bioanalysis in pharmaceutical companies in support of their drug development pipeline. This trend is largely driven by the effort to reduce internal cost, especially in support of late-stage pipeline assets where established bioanalytical assays are used to analyze a large volume of samples. This article will highlight our perspective of how bioanalytical laboratories within pharmaceutical companies can be developed into the best partner in the advancement of drug development pipelines with high-quality support at competitive cost.

  13. Opening Address [International Conference on Effective Nuclear Regulatory Systems: Further Enhancing the Global Nuclear Safety and Security Regime, Cape Town (South Africa), 14-18 December 2009

    International Nuclear Information System (INIS)

    Peters, Elizabeth Dipuo

    2010-01-01

    Nuclear energy is seen by many countries as providing a sustainable solution to energy security challenges. In this context, many developing countries are considering the establishment of nuclear power build programmes, while countries with mature nuclear programmes are considering the possibility of further expansion. The challenges facing countries that are embarking on this new venture include, inter alia, the development of policies, legislation as well as the establishment of appropriate institutions such as regulatory bodies with effective independence to take regulatory decisions. Regional and international cooperation and coordination are therefore of critical importance. Accordingly, the establishment of the Forum of Regulatory Bodies in Africa is a welcome initiative. We are pleased that the national nuclear programme in post-apartheid South Africa places us in a position to become active global participants in the safe use of nuclear energy for peaceful purposes. However, we all have an obligation to ensure that the presence of a plethora of cooperation mechanisms such as this body are as inclusive and as supportive as possible. This will help the global community of nations in reaping maximum benefits that surely should arise from these initiatives to ensure security of energy supply. We do not have the luxury to duplicate such bodies. The role of the International Atomic Energy Agency in nuclear safety and security cannot be over-emphasized. That alone is the reason that drove the liberation movement of the people of our country, and now the ruling party, fully to conform to all the treaties and conventions that have been drafted by this reputable institution of the peoples of the world. The same goes for the facilitation of cooperation and the sharing of knowledge and experience. The IAEA is invariably trusted to provide independent views and advice in order to strengthen safety and security while preserving the sovereignty, authority and

  14. Implementing nuclear non-proliferation in Finland. Regulatory control, international cooperation and the comprehensive nuclear-test-ban treaty. Annual report 2007

    International Nuclear Information System (INIS)

    Haemaelaeinen, M.; Karhu, P.

    2008-04-01

    Regulatory control of nuclear materials (nuclear safeguards) is a prerequisite for the peaceful use of nuclear energy in Finland. In order to uphold our part of the international agreements on nuclear non-proliferation - mainly the Non-Proliferation Treaty (NPT). This regulatory control is exercised by the Nuclear Materials Section of the Finnish Radiation and Nuclear Safety Authority (STUK). Nuclear safeguards are applied to all materials and activities that can lead to the proliferation of nuclear weapons or sensitive nuclear technology. These safeguards include nuclear materials accountancy, control, security and reporting. The results of STUK's nuclear safeguards inspection activities in 2007 continued to demonstrate that Finnish licence holders take good care of their nuclear materials. There were no indications of undeclared nuclear materials or activities and the inspected materials and activities were in accordance with the licence holders' declarations. STUK remarked on the nuclear safeguards systems of two licence holders in 2007, setting required actions for them to correct their reporting and to update the descriptions of their procedures. Neither the IAEA nor the European Commission made any remarks nor did they present any required actions based on their inspections. By their nuclear materials accountancy and control systems, all licence holders enabled STUK to fulfil its own obligations under the international agreements relevant to nuclear safeguards

  15. Drug Holidays From ADHD Medication: International Experience Over the Past Four Decades.

    Science.gov (United States)

    Ibrahim, Kinda; Donyai, Parastou

    2015-07-01

    ADHD is managed by stimulants that are effective but can cause growth retardation. Prescribers should ideally monitor children and trial a "drug holiday" to enable catch-up growth. Our aim was to map the experience of drug holidays from ADHD medication in children and adolescents. A comprehensive search of the literature identified 22 studies published during the period 1972 to 2013. Drug holidays are prevalent in 25% to 70% of families and are more likely to be exercised during school holidays. They test whether medication is still needed and are also considered for managing medication side effects and drug tolerance. The impact of drug holidays was reported in terms of side effects and ADHD symptoms. There was evidence of a positive impact on child growth with longer breaks from medication, and shorter breaks could reduce insomnia and improve appetite. Drug holidays from ADHD medication could be a useful tool with multiple purposes: assessment, management, prevention, and negotiation. © 2014 SAGE Publications.

  16. Nuclear Regulatory legislation

    International Nuclear Information System (INIS)

    1984-06-01

    This compilation of statutes and material pertaining to nuclear regulatory legislation through the 97th Congress, 2nd Session, has been prepared by the Office of the Executive Legal Director, U.S. Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document

  17. ASSUMING REGULATORY AUTHORITY FOR TRANSNATIONAL TORTS: AN INTERSTATE AFFAIR? A HISTORICAL PERSPECTIVE ON THE CANADIAN PRIVATE INTERNATIONAL LAW TORT RULES

    Directory of Open Access Journals (Sweden)

    Roxana Banu

    2013-02-01

    Full Text Available In Tolofson v. Jensen, the Supreme Court of Canada determined that in most cases the law of the place where the tort occurred has exclusive authority to regulate all legal aspects related to it. In developing this choice of law rule, the Supreme Court relied on an analogy between Private International Law and Public International law. This allows Private International Law to claim a structural, neutral function in the distribution of legislative authority in the international realm and to ignore both private law and public law considerations. To best reveal the way in which the Supreme Court injected these limitations into Private International Law by reference to Public International Law, I show the striking similarity between the Supreme Court’s reasoning and several Private International Law writings at the end of the 19th century in Continental Europe. In the context of the extraterritorial tortious activity of multinational corporations, these limitations make Private International Law oblivious to arguments of Corporate Social Responsibility scholars showing that a multinational corporation may legitimately be regulated by the state of its headquarters, even for extraterritorial conduct. Overall, I argue that an overemphasis on legislative authority as a symbol of state sovereignty transforms Private International Law matters generally, and transnational torts in particular, in inter-state affairs, removed from the interests and pleas of the individuals and communities affected by them.   Dans l’arrêt Tolofson c. Jensen, la Cour suprême du Canada a décidé que, dans la plupart des cas, la loi du lieu où le délit a été commis régit exclusivement tous les aspects juridiques qui s’y rapportent. Pour établir cette règle du choix de la loi applicable, la Cour suprême s’est fondée sur une analogie entre le droit international privé et le droit international public. Cela permet au droit international privé de réclamer une

  18. [The Working Group of Enforcement Officers (WGEO) : The European Network of Drug Regulatory Authorities to Combat Pharmaceutical Crime].

    Science.gov (United States)

    Wittstock, Marcus; Streit, Renz

    2017-11-01

    Ten years ago the Heads of Medicines Agencies (HMA) officially founded the Working Group of Enforcement Officers (WGEO), a European working group to reduce falsifications of human and veterinarian medicinal products in the legal and illegal supply chain. Police, customs and other international organisations are also represented in the WGEO. Partner organisations are for example the Directorate General for Health and Food Safety of the European Commission, the European Medicines Agency (EMA), the European Police Office (Europol), the International Criminal Police Organization (Interpol), the European Directorate for the Quality of Medicines and Healthcare (EDQM) and the World Health Organization (WHO). The main goal of the group is the protection of public health from harmful medicines for both humans and animals. The WGEO has created a network of its members and a rapid alert system to exchange confidential information on falsified or stolen medicinal products. There are face-to-face meetings twice a year including training using case studies.

  19. [Cancer: Is it really so different? Particularities of oncologic drugs from the perspective of the pharmaceutical regulatory agency].

    Science.gov (United States)

    Enzmann, Harald; Broich, Karl

    2013-01-01

    For innovative oncological medicines the centralised procedure at the European Medicines Agency is mandatory for a marketing authorisation application for the European Union. As with other medical drugs, the marketing authorisation decision is based on the assessment of its efficacy, safety and pharmaceutical quality but does not consider price or reimbursement. More sophisticated diagnostic methods drive an increasing stratification of cancer into a multitude of different diseases. Regardless of their different pathogenesis and therapeutic options the most relevant clinical endpoints remain cure, overall survival and progression free survival. These endpoints include both efficacy and safety, as patient survival reflects the sum of the beneficial anti-tumour effects (increasing survival) AND the adverse effects (decreasing survival). The benefit of an anticancer medicine should be evident from both overall survival and progression free survival (e.g. used as primary and secondary endpoints). Mature data on overall survival may not be needed for marketing authorisation if a clear increase in progression free survival convincingly predicts a beneficial effect on overall survival. In these exceptional cases treatment of patients with an obviously beneficial medicine must not be delayed - possibly for years - until the exact size of the benefit has been established. The continued stratification of the disease cancer results in a lower prevalence for each of the newly distinguished disease entities and an ever increasing number of orphan designations for medicines for rare diseases. Incentives for the development of orphan medicines include market exclusivity for up to ten years. In specific circumstances, however, the orphan legislation may restrict the authorisation and marketing of competing generic products even beyond these ten years. Conditional approval and approval under exceptional circumstances may accelerate patients' access to a new medicine. Both postulate

  20. The International Nexus Between Drugs and Terror: Lessons in Conflict and Diplomacy

    Science.gov (United States)

    2010-12-01

    opium, marijuana , coffee, coca, hallucinogens and many other drugs that predate history to keep themselves awake, lessen pain and increase virility...of the drugs that are mainly derived from natural plants such as cocaine, heroin and marijuana . The Convention on Psychotropic Substances of 1971...and 1972 amendment protocol of Single Convention, addressed the synthetic substances, creating provisions to regulate their trade, selling

  1. 77 FR 50113 - ASTM International-Food and Drug Administration Workshop on Absorbable Medical Devices: Lessons...

    Science.gov (United States)

    2012-08-20

    ... disability, please contact Cindy Garris, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, rm... that the implant must withstand and perform. Moreover, the optimal preclinical/bench testing paradigm...

  2. Scientific and Regulatory Policy Committee Points-to-consider Paper*: Drug-induced Vascular Injury Associated with Nonsmall Molecule Therapeutics in Preclinical Development: Part 2. Antisense Oligonucleotides.

    Science.gov (United States)

    Engelhardt, Jeffery A; Fant, Pierluigi; Guionaud, Silvia; Henry, Scott P; Leach, Michael W; Louden, Calvert; Scicchitano, Marshall S; Weaver, James L; Zabka, Tanja S; Frazier, Kendall S

    2015-10-01

    Drug-induced vascular injury (DIVI) is a recurrent challenge in the development of novel pharmaceutical agents. In recent years, DIVI has been occasionally observed in nonhuman primates given RNA-targeting therapeutics such as antisense oligonucleotide therapies (ASOs) during chronic toxicity studies. While DIVI in laboratory animal species has been well characterized for vasoactive small molecules, and immune-mediated responses against large molecule biotherapeutics have been well described, there is little published information regarding DIVI induced by ASOs to date. Preclinical DIVI findings in monkeys have caused considerable delays in development of promising new ASO therapies, because of the uncertainty about whether DIVI in preclinical studies is predictive of effects in humans, and the lack of robust biomarkers of DIVI. This review of DIVI discusses clinical and microscopic features of vasculitis in monkeys, their pathogenic mechanisms, and points to consider for the toxicologist and pathologist when confronted with ASO-related DIVI. Relevant examples of regulatory feedback are included to provide insight into risk assessment of ASO therapies. © 2015 by The Author(s).

  3. Welcome Address by H. Liu [4. International Conference on Effective Nuclear Regulatory Systems: Sustaining Improvements Globally, Vienna (Austria), 11-15 April 2016

    International Nuclear Information System (INIS)

    Liu, H.

    2017-01-01

    In his opening remarks, Mr. Liu Hua, the President of the conference, noted that the presence of so many attendees at the conference indicated a high level of interest in effective nuclear regulation. He added that effective regulatory systems are very important in maintaining and improving global nuclear safety, and that the first conference on this topic, held ten years ago, created a valuable platform for achieving that goal. In the intervening decade, through the conferences held in Moscow, Cape Town, Ottawa and Vienna, the importance of effective regulation has become more widely recognized and key elements, including independence, transparency, openness, competence and wider international cooperation, have been identified. Mr. Liu Hua pointed to specific actions proposed for governments, regulatory bodies and stakeholders, and highlighted that many of the actions had already achieved fruitful outcomes. He also noted that many lessons had been learned and many improvements had been made in the light of the Fukushima Daiichi accident: 1. To further improve government infrastructure; 2. To further improve nuclear safety standards; 3. To further develop regulation capacity building and human resource; 4. To further enhance knowledge and experience management and transition, 5. To further foster and strengthen nuclear safety culture; 6. To further improve and rebuild public confidence

  4. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2008-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  5. [Prevalence and factors associated with clinical counselling on drug use among internal specialists residents of Andalusia (Spain)].

    Science.gov (United States)

    Juárez-Jiménez, María de la Villa; Pérez-Milena, Alejandro; Valverde-Bolívar, Francisco Javier; Rosa-Garrido, Carmen

    2015-12-01

    To determine the frequency of offering clinical counseling against the consumption of alcohol, tobacco and illegal drugs by internal specialist residents (EIR) of Andalusia, and the factors related to such advice. Multicenter cross-sectional study by self-administered questionnaire sent by mail. EIR of Andalusia. The questionnaire collected the frequency of counseling against the use of alcohol, tobacco and illegal drugs (dependent variable). age/gender, specialty, drug consumption and Fagerström test. Out of a total of 4245 participants, 66% responded, 29% did not respond, and 5% poorly completed questionnaires. The mean age was 29.1(±SD 5.1) years, 69% female, 89% Spanish nationality, 84% in medical training (73% hospital, 27% family medicine). The frequency of counseling against tobacco (85%) and alcohol (82%) is higher than illegal drugs (56%, pformative elements of their own specialty such as personal consumption of alcohol and tobacco, which should be considered for improvement of this preventive activity. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  6. International conference on the strengthening of nuclear safety in Eastern Europe. Keynote papers. Regulatory aspects of NPP safety, status of safety improvements, status of safety analysis report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-06-01

    The Objective of the Conference was to assess the past decade of nuclear safety efforts in countries operating WWER and RBMK nuclear reactors and to address remaining safety issues which require further work. A particular focus of the Conference was on international co-operation and assistance and where such efforts should be focused in the future. All Eastern European countries that operate RBMK or WWER reactors participated in the Conference, and presented papers on three key areas of nuclear safety: Regulatory Aspects of Nuclear Power Plant Safety; Status of Safety Improvements; and Status of Safety Analysis Reports. In addition, representatives from 18 additional countries that provide financial and/or technical assistance and co-operation in the area of WWER and RBMK safety offered the most extensive commentary. Key international (IAEA, World Association of Nuclear Operators, the Nuclear Energy Agency, the G-24 NUSAC, the European Commission, and the EBRD) organizations that provide nuclear safety assistance for WWER and RBMK reactors also made presentations. There is no question that considerable progress on nuclear safety has been made in Eastern Europe. Special mention should be made of successful efforts to strengthen the independence and technical competence of the nuclear regulatory authorities. Efforts should now concentrate on improving the depth and scope of the technical abilities of the regulatory authorities. More attention by governments is needed to ensure that the regulatory authorities have the financial resources and enforcement authority to fully execute their missions. In respect to the operators of the nuclear power plants, they have demonstrated clear progress in operational safety improvements. Significant additional efforts are required to maintain and enhance an effective safety culture. Design safety improvement programmes are in place in all countries. Implementation of these programmes has varied and is particularly affected by

  7. International conference on the strengthening of nuclear safety in Eastern Europe. Keynote papers. Regulatory aspects of NPP safety, status of safety improvements, status of safety analysis report

    International Nuclear Information System (INIS)

    1999-06-01

    The Objective of the Conference was to assess the past decade of nuclear safety efforts in countries operating WWER and RBMK nuclear reactors and to address remaining safety issues which require further work. A particular focus of the Conference was on international co-operation and assistance and where such efforts should be focused in the future. All Eastern European countries that operate RBMK or WWER reactors participated in the Conference, and presented papers on three key areas of nuclear safety: Regulatory Aspects of Nuclear Power Plant Safety; Status of Safety Improvements; and Status of Safety Analysis Reports. In addition, representatives from 18 additional countries that provide financial and/or technical assistance and co-operation in the area of WWER and RBMK safety offered the most extensive commentary. Key international (IAEA, World Association of Nuclear Operators, the Nuclear Energy Agency, the G-24 NUSAC, the European Commission, and the EBRD) organizations that provide nuclear safety assistance for WWER and RBMK reactors also made presentations. There is no question that considerable progress on nuclear safety has been made in Eastern Europe. Special mention should be made of successful efforts to strengthen the independence and technical competence of the nuclear regulatory authorities. Efforts should now concentrate on improving the depth and scope of the technical abilities of the regulatory authorities. More attention by governments is needed to ensure that the regulatory authorities have the financial resources and enforcement authority to fully execute their missions. In respect to the operators of the nuclear power plants, they have demonstrated clear progress in operational safety improvements. Significant additional efforts are required to maintain and enhance an effective safety culture. Design safety improvement programmes are in place in all countries. Implementation of these programmes has varied and is particularly affected by

  8. The contribution of internal resources, external resources, and emotional distress to use of drugs and alcohol among Israeli Jewish urban adolescents.

    Science.gov (United States)

    Lipschitz-Elhawi, Racheli; Itzhaky, Haya

    2014-03-01

    The contribution of selected background variables (age, gender), internal resources (mastery, emotional maturity), external resources (parental and peer support), and emotional distress to alcohol and drug use among 160 Israeli Jewish urban high school students were examined. Analyzing the variables with hierarchical regression, emotional distress contributed most significantly to both alcohol and drug use, and the contribution of age was somewhat less significant for both of them. Emotional distress also contributed indirectly to drug use through an interaction with one's sense of mastery. Gender, internal resources, and external resources contributed differentially to alcohol and drug use. Whereas gender and internal resources contributed only to drug use, external resources contributed only to alcohol use. Specifically, peer support contributed positively to alcohol use whereas parental support contributed negatively. The discussion provides explanations for these research findings and their implications, and the research's limitations are noted.

  9. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel.

    Science.gov (United States)

    Günthard, Huldrych F; Saag, Michael S; Benson, Constance A; del Rio, Carlos; Eron, Joseph J; Gallant, Joel E; Hoy, Jennifer F; Mugavero, Michael J; Sax, Paul E; Thompson, Melanie A; Gandhi, Rajesh T; Landovitz, Raphael J; Smith, Davey M; Jacobsen, Donna M; Volberding, Paul A

    2016-07-12

    New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and

  10. 78 FR 79465 - International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on...

    Science.gov (United States)

    2013-12-30

    ... harmful physical, mental, and social consequences for the user or to others. Harmful use of drugs by an...... --Please provide any information on the extent/magnitude of public health or social harm from the use of... medical illnesses caused by this substance in your country? (Yes/ No) If ``yes,'' please provide details...

  11. 77 FR 26768 - Food and Drug Administration/International Society for Pharmaceutical Engineering Cosponsorship...

    Science.gov (United States)

    2012-05-07

    ... ISPE room block is filled). If you need special accommodations due to a disability, please contact ISPE.... Topics for discussion include the following: (1) The Business Case For Change; (2) Quality Risk... Network; (4) IT Strategies--Cloud Computing, RFID, and Beyond; (5) The Future of Drug Manufacturing. To...

  12. International comparison of the factors influencing reimbursement of targeted anti-cancer drugs.

    Science.gov (United States)

    Lim, Carol Sunghye; Lee, Yun-Gyoo; Koh, Youngil; Heo, Dae Seog

    2014-11-29

    Reimbursement policies for anti-cancer drugs vary among countries even though they rely on the same clinical evidence. We compared the pattern of publicly funded drug programs and analyzed major factors influencing the differences. We investigated reimbursement policies for 19 indications with targeted anti-cancer drugs that are used variably across ten countries. The available incremental cost-effectiveness ratio (ICER) data were retrieved for each indication. Based on the comparison between actual reimbursement decisions and the ICERs, we formulated a reimbursement adequacy index (RAI): calculating the proportion of cost-effective decisions, either reimbursement of cost-effective indications or non-reimbursement of cost-ineffective indications, out of the total number of indications for each country. The relationship between RAI and other indices were analyzed, including governmental dependency on health technology assessment, as well as other parameters for health expenditure. All the data used in this study were gathered from sources publicly available online. Japan and France were the most likely to reimburse indications (16/19), whereas Sweden and the United Kingdom were the least likely to reimburse them (5/19 and 6/19, respectively). Indications with high cost-effectiveness values were more likely to be reimbursed (ρ = -0.68, P = 0.001). The three countries with high RAI scores each had a healthcare system that was financed by general taxation. Although reimbursement policies for anti-cancer drugs vary among countries, we found a strong correlation of reimbursements for those indications with lower ICERs. Countries with healthcare systems financed by general taxation demonstrated greater cost-effectiveness as evidenced by reimbursement decisions of anti-cancer drugs.

  13. IAEA meeting: International conference of national regulatory authorities with competence in the safety of radiation sources and the security of radioactive materials

    Energy Technology Data Exchange (ETDEWEB)

    Englefield, Chris [UK INTERPOL Environmental Crime (Radioactive Substances) Sub-Group, Environment Agency (United Kingdom)

    2001-06-01

    The meeting was the outcome of one of the actions arising from an IAEA sponsored meeting held in Dijon in 1998 on these issues. The action plan included inter alia the production of a 'Code of Conduct' (published December 2000), the production of a scheme for the 'Categorisation of Sources' (published December 2000) and a meeting to share experience and knowledge about the issues of illicit or inadvertent movements of radioactive materials across international borders. This was the major focus of the meeting held in Buenos Aires. The meeting was attended by 130 delegates representing 70 countries, the EU and the IAEA. This means that over half of the 131 IAEA Member States were present, a measure of the level of significance that is attached to the initiating issue of 'illicit trafficking'.The meeting was chaired by Dan Beninson (Argentina) and the Technical Secretariat was led by Alfonso Bilbao of IAEA. I attended as the UK delegate, in my capacity as Chairman of the UK INTERPOL Environmental Crime (Radioactive Substances) Sub-Group. The national papers were so numerous that it is not practicable to try to summarise them all here. However, a general impression will be given. The majority of papers submitted explained the regulatory structures extant in the speakers' home countries. It was useful to understand the level of development of regulatory arrangements in the Member States represented. These ranged from the highly developed such as those of EU Member States, the US and some South American states, to the very simple. In some cases, speakers frankly admitted that regulatory systems were virtually non-existent, but that as IAEA Members, their countries were ready and willing to improve their arrangements, with the assistance of IAEA . Some general conclusions may be derived: (i) A personal view is that IAEA and Member States have not clarified their risk assessment thinking: as RP practitioners we tend to concentrate on

  14. Why are generic drugs being held up in transit? Intellectual property rights, international trade, and the right to health in Brazil and beyond.

    Science.gov (United States)

    Rosina, Mônica Steffen Guise; Shaver, Lea

    2012-01-01

    Access to medicines faces a new legal threat: "border enforcement" of drug patents. Using Brazil as an example, this article shows how the right to health depends on international trade. Border seizures of generic drugs present human rights and trade institutions with a unique challenge. Can public health advocates rise to meet it? © 2012 American Society of Law, Medicine & Ethics, Inc.

  15. Lactobacillus plantarum Strains Can Enhance Human Mucosal and Systemic Immunity and Prevent Non-steroidal Anti-inflammatory Drug Induced Reduction in T Regulatory Cells

    Science.gov (United States)

    de Vos, Paul; Mujagic, Zlatan; de Haan, Bart J.; Siezen, Roland J.; Bron, Peter A.; Meijerink, Marjolein; Wells, Jerry M.; Masclee, Ad A. M.; Boekschoten, Mark V.; Faas, Marijke M.; Troost, Freddy J.

    2017-01-01

    Orally ingested bacteria interact with intestinal mucosa and may impact immunity. However, insights in mechanisms involved are limited. In this randomized placebo-controlled cross-over trial, healthy human subjects were given Lactobacillus plantarum supplementation (strain TIFN101, CIP104448, or WCFS1) or placebo for 7 days. To determine whether L. plantarum can enhance immune response, we compared the effects of three stains on systemic and gut mucosal immunity, by among others assessing memory responses against tetanus toxoid (TT)-antigen, and mucosal gene transcription, in human volunteers during induction of mild immune stressor in the intestine, by giving a commonly used enteropathic drug, indomethacin [non-steroidal anti-inflammatory drug (NSAID)]. Systemic effects of the interventions were studies in peripheral blood samples. NSAID was found to induce a reduction in serum CD4+/Foxp3 regulatory cells, which was prevented by L. plantarum TIFN101. T-cell polarization experiments showed L. plantarum TIFN101 to enhance responses against TT-antigen, which indicates stimulation of memory responses by this strain. Cell extracts of the specific L. plantarum strains provoked responses after WCFS1 and TIFN101 consumption, indicating stimulation of immune responses against the specific bacteria. Mucosal immunomodulatory effects were studied in duodenal biopsies. In small intestinal mucosa, TIFN101 upregulated genes associated with maintenance of T- and B-cell function and antigen presentation. Furthermore, L. plantarum TIFN101 and WCFS1 downregulated immunological pathways involved in antigen presentation and shared downregulation of snoRNAs, which may suggest cellular destabilization, but may also be an indicator of tissue repair. Full sequencing of the L. plantarum strains revealed possible gene clusters that might be responsible for the differential biological effects of the bacteria on host immunity. In conclusion, the impact of oral consumption L. plantarum on

  16. Lactobacillus plantarum Strains Can Enhance Human Mucosal and Systemic Immunity and Prevent Non-steroidal Anti-inflammatory Drug Induced Reduction in T Regulatory Cells

    Directory of Open Access Journals (Sweden)

    Paul de Vos

    2017-08-01

    Full Text Available Orally ingested bacteria interact with intestinal mucosa and may impact immunity. However, insights in mechanisms involved are limited. In this randomized placebo-controlled cross-over trial, healthy human subjects were given Lactobacillus plantarum supplementation (strain TIFN101, CIP104448, or WCFS1 or placebo for 7 days. To determine whether L. plantarum can enhance immune response, we compared the effects of three stains on systemic and gut mucosal immunity, by among others assessing memory responses against tetanus toxoid (TT-antigen, and mucosal gene transcription, in human volunteers during induction of mild immune stressor in the intestine, by giving a commonly used enteropathic drug, indomethacin [non-steroidal anti-inflammatory drug (NSAID]. Systemic effects of the interventions were studies in peripheral blood samples. NSAID was found to induce a reduction in serum CD4+/Foxp3 regulatory cells, which was prevented by L. plantarum TIFN101. T-cell polarization experiments showed L. plantarum TIFN101 to enhance responses against TT-antigen, which indicates stimulation of memory responses by this strain. Cell extracts of the specific L. plantarum strains provoked responses after WCFS1 and TIFN101 consumption, indicating stimulation of immune responses against the specific bacteria. Mucosal immunomodulatory effects were studied in duodenal biopsies. In small intestinal mucosa, TIFN101 upregulated genes associated with maintenance of T- and B-cell function and antigen presentation. Furthermore, L. plantarum TIFN101 and WCFS1 downregulated immunological pathways involved in antigen presentation and shared downregulation of snoRNAs, which may suggest cellular destabilization, but may also be an indicator of tissue repair. Full sequencing of the L. plantarum strains revealed possible gene clusters that might be responsible for the differential biological effects of the bacteria on host immunity. In conclusion, the impact of oral consumption L

  17. Unregulated usage of labour-inducing medication in a region of Pakistan with poor drug regulatory control: characteristics and risk patterns.

    Science.gov (United States)

    Shah, Safieh; Van den Bergh, Rafael; Prinsloo, Jeanne Rene; Rehman, Gulalai; Bibi, Amna; Shaeen, Neelam; Auat, Rosa; Daudi, Sabina Mutindi; Njenga, Joyce Wanjiru; Khilji, Tahir Bashir-Ud-Din; Maïkéré, Jacob; De Plecker, Eva; Caluwaerts, Séverine; Zachariah, Rony; Van Overloop, Catherine

    2016-03-01

    In developing countries such as Pakistan, poor training of mid-level cadres of health providers, combined with unregulated availability of labour-inducing medication can carry considerable risk for mother and child during labour. Here, we describe the exposure to labour-inducing medication and its possible risks in a vulnerable population in a conflict-affected region of Pakistan. A retrospective cohort study using programme data, compared the outcomes of obstetric risk groups of women treated with unregulated oxytocin, with those of women with regulated treatment. Of the 6379 women included in the study, 607 (9.5%) received labour-inducing medication prior to reaching the hospital; of these, 528 (87.0%) received unregulated medication. Out of 528 labour-inducing medication administrators, 197 (37.3%) traditional birth attendants (also known as dai) and 157 (29.7%) lady health workers provided unregulated treatment most frequently. Women given unregulated medication who were diagnosed with obstructed/prolonged labour were at risk for uterine rupture (RR 4.1, 95% CI: 1.7-9.9) and severe birth asphyxia (RR 3.9, 95% CI: 2.5-6.1), and those with antepartum haemorrhage were at risk for stillbirth (RR 1.8, 95% CI: 1.0-3.1). In a conflict-affected region of Pakistan, exposure to unregulated treatment with labour-inducing medication is common, and carries great risk for mother and child. Tighter regulatory control of labour-inducing drugs is needed, and enhanced training of the mid-level cadres of healthcare workers is required. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

  18. [Direct costs and clinical aspects of adverse drug reactions in patients admitted to a level 3 hospital internal medicine ward].

    Science.gov (United States)

    Tribiño, Gabriel; Maldonado, Carlos; Segura, Omar; Díaz, Jorge

    2006-03-01

    Adverse drug reactions (ADRs) occur frequently in hospitals and increase costs of health care; however, few studies have quantified the clinical and economic impact of ADRs in Colombia. These impacts were evaluated by calculating costs associated with ADRs in patients hospitalized in the internal medicine ward of a Level 3 hospital located in Bogotá, Colombia. In addition, salient clinical features of ADRs were identified and characterized. Intensive follow-ups for a cohort of patients were conducted for a five month period in order to detect ADRs; different ways to classify them, according to literature, were considered as well. Information was collected using the INVIMA reporting format, and causal probability was evaluated with the Naranjo algorithm. Direct costs were calculated from the perspective of payer, based on the following costs: additional hospital stay, medications, paraclinical tests, additional procedures, patient displacement to intermediate or intensive care units, and other costs. Of 836 patients admitted to the service, 268 adverse drug reactions were detected in 208 patients (incidence proportion 25.1%, occurence rate 0.32). About the ADRs found, 74.3% were classified as probable, 92.5% were type A, and 81.3% were moderate. The body system most often affected was the circulatory system (33.9%). Drugs acting on the blood were most frequently those ones associated with adverse reactions (37.6%). The costs resulting from medical care of adverse drug reactions varied from COL dollar 93,633,422 (USD dollar 35,014.92) to COL dollar 122,155,406 (USD dollar 45,680.94), according to insurance type, during the study period. Adverse drug reactions have a significant negative health and financial impact on patient welfare. Because of the substantial resources required for their medical care and the significant proportion of preventable adverse reactions, active programs of institutional pharmacovigilance are highly recommended.

  19. INTERNATIONAL REGULATORY DOCUMENTS WITH SPECIAL REGIME USED BY ROMANIAN PRINCIPALITIES IN RELATIONS WITH THE OTTOMAN AND THE RUSSIAN EMPIRE

    Directory of Open Access Journals (Sweden)

    Ion Gr. IONESCU

    2015-11-01

    Full Text Available Although the existence of some regulating documents, called capitulations, concerning the relations on various plans, between the Romanian Country, Moldavia and the Ottoman Empire was known, the first one of these diplomatic documents, that have been operational over time, was discovered only in 1974. It was an act that had been granted to Mihnea Turkished, in the year 1585. This important discovery has been completed, with others that had the same purpose. In fact, they were some diplomatic documents, with the role of Treaty, which has regulated quite explicitly, the status of the two Romanian principalities, in relations with the suzerain power. The most important fact of their contents was the recognition of the internal autonomy of principalities and a certain degree of freedom, in relations outside the borders. The price was that Romanian countries paid was ,however, to never become hostile to Ottoman interests, integrating in the Ottoman foreign policy and paying an annual tribute.

  20. The Role of Internalized Stigma in the Disclosure of Injecting Drug Use Among People Who Inject Drugs and Self-Report as HIV-Positive in Kohtla-Järve, Estonia.

    Science.gov (United States)

    Johannson, Annika; Vorobjov, Sigrid; Heimer, Robert; Dovidio, John F; Uusküla, Anneli

    2017-04-01

    Disclosure of injecting drug use and its associations with stigma have received very little research attention. This cross-sectional study examined the role of internalized HIV and drug stigma (i.e., self-stigmatization) in the disclosure of injecting drug use among people who inject drugs (PWID) self-reporting as HIV-positive (n = 312) in Kohtla-Järve, Estonia. The internalization of both stigmas was relatively high. On average, PWID disclosed to three disclosure targets out of seven. Disclosure was highest to close friends and health care workers and lowest to employers and casual sex partners. Internalized drug stigma was negatively associated with disclosure to other family members (AOR = 0.48; 95% CI 0.30-0.77) and health care workers (AOR = 0.46; 95% CI 0.25-0.87). Internalized HIV stigma was positively associated with disclosure to health care workers (AOR = 2.26; 95% CI 1.27-4.00). No interaction effect of internalized stigmas on disclosures emerged. We concluded that effects of internalized stigmas on disclosures are few and not uniform.

  1. International Drug Trafficking--a Growing National Security Concern for Low Intensity Conflict

    Science.gov (United States)

    1990-03-01

    nations were economically undermined by trade barriers against their exports to the U.S., e.g., coffee and sugar, which further degraded their financial...applied. A second focus of our strategy must be to discourage still minor cannabis producers in Central and South 76 International Initiatives America

  2. International comparative analysis of E and P regulatory issues; Analise comparativa internacional de aspectos regulatorios em E e P

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Erica Cristina da Fonseca; Almedia, Mariana Lessa Rego de; Baleroni, Rafael Baptista [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Faculdade de Direito

    2004-07-01

    The oil industry is one of the more global sectors of the economy, with its economic agents acting and competing at the same time in many countries. The limitation of available funds for investment and competition in global scale make the host countries adapt some elements of their concession instruments, as a way to attract greater investments. The comparison of legal framework of diverse host countries is an essential part in this process of decision and an indispensable tool to help the host countries in the dispute for the attraction of international investors. Therefore, to place Brazil in this process of global competition between States is necessary the knowledge and the comparison between the conditions offered for its legal system and offered for countries considered as models of attraction of investment. This work intends to offer a comparative study of relevant legal aspects for the oil industry, amongst them: characterization of the concession instrument; reach of the participation of the state-owned company; intervention of the State in the private management. The comparison will be made between countries with different characteristics, to obtain a consolidation of paradigms that helps the evolution of the Brazilian exploration and production legal framework. (author)

  3. The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets.

    Science.gov (United States)

    Kulinowski, Piotr; Hudy, Wiktor; Mendyk, Aleksander; Juszczyk, Ewelina; Węglarz, Władysław P; Jachowicz, Renata; Dorożyński, Przemysław

    2016-06-01

    In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas-e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products.

  4. Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis.

    Science.gov (United States)

    Ong, Edmund; Cahill, Catherine

    2015-07-03

    The intracellular trafficking of receptors is a collection of complex and highly controlled processes. Receptor trafficking modulates signaling and overall cell responsiveness to ligands and is, itself, influenced by intra- and extracellular conditions, including ligand-induced signaling. Optimized for use with monolayer-plated cultured cells, but extendable to free-floating tissue slices, this protocol uses immunolabelling and colocalizational analysis to track changes in intracellular receptor trafficking following both chronic/prolonged and acute interventions, including exogenous drug treatment. After drug treatment, cells are double-immunolabelled for the receptor and for markers for the intracellular compartments of interest. Sequential confocal microscopy is then used to capture two-channel photomicrographs of individual cells, which are subjected to computerized colocalizational analysis to yield quantitative colocalization scores. These scores are normalized to permit pooling of independent replicates prior to statistical analysis. Representative photomicrographs may also be processed to generate illustrative figures. Here, we describe a powerful and flexible technique for quantitatively assessing induced receptor trafficking.

  5. The predictive power of family history measures of alcohol and drug problems and internalizing disorders in a college population.

    Science.gov (United States)

    Kendler, Kenneth S; Edwards, Alexis; Myers, John; Cho, Seung Bin; Adkins, Amy; Dick, Danielle

    2015-07-01

    A family history (FH) of psychiatric and substance use problems is a potent risk factor for common internalizing and externalizing disorders. In a large web-based assessment of mental health in college students, we developed a brief set of screening questions for a FH of alcohol problems (AP), drug problems (DP) and depression-anxiety in four classes of relatives (father, mother, aunts/uncles/grandparents, and siblings) as reported by the student. Positive reports of a history of AP, DP, and depression-anxiety were substantially correlated within relatives. These FH measures predicted in the student, in an expected pattern, dimensions of personality and impulsivity, alcohol consumption and problems, smoking and nicotine dependence, use of illicit drugs, and symptoms of depression and anxiety. Using the mean score from the four classes of relatives was more predictive than using a familial/sporadic dichotomy. Interactions were seen between the FH of AP, DP, and depression-anxiety and peer deviance in predicting symptoms of alcohol and tobacco dependence. As the students aged, the FH of AP became a stronger predictor of alcohol problems. While we cannot directly assess the validity of these FH reports, the pattern of findings suggest that our brief screening items were able to assess, with some accuracy, the FH of substance misuse and internalizing psychiatric disorders in relatives. If correct, these measures can play an important role in the creation of developmental etiologic models for substance and internalizing psychiatric disorders which constitute one of the central goals of the overall project. © 2015 Wiley Periodicals, Inc.

  6. Internal medicine residency training for unhealthy alcohol and other drug use: recommendations for curriculum design

    Science.gov (United States)

    2010-01-01

    Background Unhealthy substance use is the spectrum from use that risks harm, to use associated with problems, to the diagnosable conditions of substance abuse and dependence, often referred to as substance abuse disorders. Despite the prevalence and impact of unhealthy substance use, medical education in this area remains lacking, not providing physicians with the necessary expertise to effectively address one of the most common and costly health conditions. Medical educators have begun to address the need for physician training in unhealthy substance use, and formal curricula have been developed and evaluated, though broad integration into busy residency curricula remains a challenge. Discussion We review the development of unhealthy substance use related competencies, and describe a curriculum in unhealthy substance use that integrates these competencies into internal medicine resident physician training. We outline strategies to facilitate adoption of such curricula by the residency programs. This paper provides an outline for the actual implementation of the curriculum within the structure of a training program, with examples using common teaching venues. We describe and link the content to the core competencies mandated by the Accreditation Council for Graduate Medical Education, the formal accrediting body for residency training programs in the United States. Specific topics are recommended, with suggestions on how to integrate such teaching into existing internal medicine residency training program curricula. Summary Given the burden of disease and effective interventions available that can be delivered by internal medicine physicians, teaching about unhealthy substance use must be incorporated into internal medicine residency training, and can be done within existing teaching venues. PMID:20230607

  7. Information for Consumers (Drugs)

    Science.gov (United States)

    ... approved drugs Drugs@FDA Information on FDA-approved brand name and generic drugs including labeling and regulatory history Drugs with Approved Risk Evaluation and Mitigation Strategies (REMS) REMS is a risk management plan required by FDA for certain prescription drugs, ...

  8. Value Assessment in the Regulatory Context.

    Science.gov (United States)

    Miller, Kathleen L; Woodcock, Janet

    2017-02-01

    Value assessments are made on new drugs before they even enter the market. Regulators at the Center for Drug Evaluation and Research (CDER) at the US Food and Drug Administration make a clinical benefit-risk assessment to determine whether to approve a new drug. Benefits of a drug are typically quantified directly, as an assessment of efficacy. CDER defines risk as the intersection of the severity of possible harm and the probability of that harm. For a novel drug to be approved, its benefits and risks must be well understood, and the trade-off between the two must be acceptable. To assist with these benefit-risk value assessments, CDER has two ongoing initiatives: the Patient-Focused Drug Development Initiative that aims to substantially increase the role of patient voice in the regulatory process, and a transparency initiative that focuses on creating a structured framework for benefit-risk assessment. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  9. Emergency control center of the nuclear Regulatory Authority: a national, regional and international tool to coordinate the response to radiological and nuclear emergencies

    International Nuclear Information System (INIS)

    Jordan, Osvaldo; Hernandez, Daniel; Telleria, Diego; Bruno, Hector; Boutet, Luis; Kunst, Juan; Sadaniowski, Ivana; Rey, Hugo

    2008-01-01

    Full text: In the year 1998, with the regulation of the Nuclear Law, the Nuclear Regulatory Authority (ARN) is constituted as the national coordinator of the response in case of nuclear or radiological emergencies. The ARN builds his first operative center installed in his Head quarter in Buenos Aires. Likewise, from the obligations that come with the Convention of Early Notification of a Nuclear Accident and Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency, the ARN is the National Warning Point and the National Competent Authority. Therefore, the operative capacity of the center needs to be expanded to cover not only the national territory but also its link with the region and the IAEA, as an access point to the International community, as the conventions demand. For the purpose of giving ARN capacities which reflect the state of art at the international level on Nuclear Emergency Centers and warrant that its equipment and technology will be compatible with those abroad (mainly with IAEA), the ARN made an arrangements with Department of Energy of United States, in the framework of an existing bilateral Argentine Foreign Office/US Government agreement (Joint Standing Committee on Nuclear Cooperation). This agreement allows a deep experience exchange, high level specialists support and last generation equipment access. As a result, the center of ARN can be considerate as the most advanced civil nuclear emergency center in the region. This work describes the implementation process of the emergency center and the technical features, like the physical distribution, hardware and software resources, communication equipment, Geographic Information Systems, etc. (author)

  10. How Do Drug Prices Respond to a Change from External to Internal Reference Pricing?

    DEFF Research Database (Denmark)

    Kaiser, Ulrich; Mendez, Susan J.

    (where they are based on the cheapest domestic substitute). We analyze three therapeutic classes with different treatment durations and show that the reform led to substantial price decreases for our lifelong treatment and to less substantial price reductions for our medium duration treatment while we do......We study the effects of a change in the way patient reimbursements are calculated on the prices of pharmaceuticals using quasi-experimental data for Denmark which switched from external (where reimbursements are based on prices of similar products in foreign countries) to internal reference pricing...

  11. Compliance of national radiation protection regulatory infrastructure with international norms: a prerequisite for self-sustainability of technical support organization in a small 'non-nuclear' country: example of Montenegro

    International Nuclear Information System (INIS)

    Jovanovic, Slobodan

    2008-01-01

    Full text: Regulatory control of radiation sources in a country is based upon two essential elements of regulatory infrastructure: national RP legislation system (including nuclear law and subsequent regulations) at one side and institutions regulatory authority (RA) and technical support organizations (TSO) at the other. International norms and standards in radiation protection are (or should be, in principle) transposed through international legal instruments (conventions, treaties, directives, codes) into national regulatory systems, thus making radiation protection regulatory practices standardized and omnipresent. We know, however, that this is often not the case, to more or less extent. More one goes down the pyramid (i.e. from international norms via national regulatory infrastructure to actual RP practice), more there is chance that ultimate/bottom practical actions will not be undertaken properly, or even not at all. One of the key elements in the above mentioned (potentially problematic) RP bottom level is how technical support to regulatory authority is organized. RP legal requirements create a market of services to be effectuated by competent professional organizations, TSO 's. In a small country, there is usually not more than one (if any) of the kind not rarely just surviving at the edge of existence. A TSO scope of RP interests/activities typically include: (1) radiation monitoring and measurements in the environment (air, soil, waters, biota), as well as in public areas, working and living places, (2) personal, workplace and field dosimetry, (3) import, export and trade control of radioactivity in food, forage, construction materials, toys, cosmetics and other goods/consumables, (4) quality control (QC) of radiation sources in medicine, industry, etc., (5) low/medium activity radioactive waste management, (6) transport of radioactive materials, (7) a role in national radiological emergency preparedness and response scheme and (8) advisory services

  12. Analysis of cocaine and its adulterants in drugs for international trafficking seized by the Brazilian Federal Police.

    Science.gov (United States)

    Lapachinske, Silvio Fernandes; Okai, Guilherme Gonçalves; dos Santos, Ariana; de Bairros, André Valle; Yonamine, Mauricio

    2015-02-01

    Here, gas chromatography with nitrogen phosphorous detector (GC-NPD) method was developed and validated for the quantification of cocaine and adulterants (caffeine, 4-dimethylaminoantipyrine, levamisole, lidocaine and phenacetin) in illicit samples. The method was based on direct dilution of samples in methanol, sonication for 5 min and centrifugation. After appropriate dilution, an aliquot was injected into GC-MS in order to identify the active compounds and into GC-NPD for the analytes quantification. Bupivacaine was used as an internal standard. The method showed to be precise, accurate and linear over a range of 0.5-100% (weight/weight percentages) for all analytes, except phenacetin which showed a linear range between 2% and 100%. The method was successfully applied to 54 samples seized by the Brazilian Federal Police in the International Airport of Sao Paulo and mailing services during the year 2011. All the samples were associated with international trafficking and were apprehended while leaving the country. The purity of cocaine ranged from 16.5% to 91.4%. Cocaine was the only detected active compound in 29.6% of total samples. Among the identified cutting agents, levamisole was the most abundant (55.6% of the total samples) and relative concentrations (weight/weight percentages) ranged from 0.7% to 23%. Lidocaine, caffeine, phenacetin and 4-dimethylaminoantipyrine were also identified in these samples in minor concentrations. In contrast with what we initially hypothesized, drugs intended to international trafficking did not present high cocaine purity and most of the samples were laced with adulterants before leaving Brazil. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. A validation of the new definition of drug-resistant epilepsy by the International League Against Epilepsy.

    Science.gov (United States)

    Téllez-Zenteno, Jose F; Hernández-Ronquillo, Lizbeth; Buckley, Samantha; Zahagun, Ricardo; Rizvi, Syed

    2014-06-01

    To establish applicability, the recently proposed International League Against Epilepsy (ILAE) consensus on drug-resistant epilepsy (DRE) requires testing in clinical and research settings. This study evaluates the reliability and validity of these criteria in a clinical population. In phase I, two independent evaluators reviewed 97 randomly selected medical records of patients with epilepsy at two separate intervals. Both ILEA consensus and standard diagnostic criteria were employed. Kappa, weighted kappa, and intraclass correlation coefficient (ICC) were used to determine interobserver and intraobserver variability. In phase II, ILAE consensus criteria were applied to 250 patients with epilepsy to determine risk factors associated with development of DRE and to calculate point prevalence. The interobserver agreement of the four definitions was as follows: Berg (0.56), Kwan and Brodie (0.58), Camfield and Camfield (0.69), and ILAE (0.77). The intraobserver agreement of the four definition was as follows: Berg (0.81), Kwan and Brodie (0.82), Camfield and Camfield (0.72), and ILAE (0.82). The prevalence of DRE was the following: with the Berg's definition was 28.4%, Kwan and Brodie 34%, Camfield and Camfield 37%, and with ILAE was 33%. This is first study to establish reliability and validity of ILAE criteria for the diagnosis of DRE. This new definition compares favorably with previously established constructs, which continue to retain clinical significance. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  14. Internalized Homophobia and Drug Use in a National Cohort of Gay and Bisexual Men: Examining Depression, Sexual Anxiety, and Gay Community Attachment as Mediating Factors.

    Science.gov (United States)

    Moody, Raymond L; Starks, Tyrel J; Grov, Christian; Parsons, Jeffrey T

    2018-05-01

    The minority stress process of internalized homophobia (IH) has been associated with a range of adverse health outcomes among gay and bisexual men (GBM). However, evidence is mixed regarding the effect of IH on drug use, suggesting the potential role of multiple mediated pathways. Researchers have linked depression, sexual anxiety, and gay community attachment with IH. Depression, sexual anxiety, and gay community attachment have also been linked with drug use and drug-related problems suggesting potential mediating roles. A U.S. national sample of 1071 HIV-negative GBM completed at-home surveys, including measures of sociodemographic characteristics, IH, depression, sexual anxiety, gay community attachment, and drug use and associated problems. Adjusting for sociodemographic characteristics, depression mediated the association between IH and recent drug use. IH was positively associated with depression, and depression was positively associated with recent drug use. Gay community attachment partially mediated drug-related problems. IH had a positive direct association with drug-related problems and a negative direct association with gay community attachment. Gay community attachment had a positive association with drug-related problems. IH was positively associated with sexual anxiety, but sexual anxiety was not associated with either drug outcome. Efforts to reduce IH among HIV-negative GBM are likely to have a positive impact on mental health problems, as well as reduce risk for drug use and drug-related problems. Gay communities could provide the social support necessary for reducing IH; however, emphasis on community level interventions that address factors that increase risk for drug-related problems remains important.

  15. Reduction in chlorhexidine efficacy against multi-drug-resistant Acinetobacter baumannii international clone II.

    Science.gov (United States)

    Hayashi, M; Kawamura, K; Matsui, M; Suzuki, M; Suzuki, S; Shibayama, K; Arakawa, Y

    2017-03-01

    Nosocomial infections caused by Acinetobacter baumannii international clone II (IC II) can cause severe clinical outcomes. Differential evaluation of bactericidal efficacy of chlorhexidine gluconate (CHX) and benzethonium chloride (BZT) disinfectants against IC II and non-IC II isolates. Minimum inhibitory concentrations (MICs) of CHX and BZT were determined for 137 A. baumannii IC II, 99 non-IC II and 69 non-baumannii isolates, further classified according to MIC values into disinfectant-reduced susceptible (DRS) and disinfectant-susceptible (DS) groups. Time-kill curves and minimum bactericidal concentrations (MBCs) were evaluated for representative isolates in each group. CHX and BZT MIC 90 s for IC II isolates were 100 and 175mg/L, respectively, but those for non-IC II and non-baumannii isolates were <100mg/L. Nevertheless, time-kill curves indicated that CHX and BZT reduced live bacterial cell number by 5 log 10 for IC II and non-IC II isolates within 30s when used at 1000mg/L, comparable to practical use concentrations. CHX MBC at 30s was 1000mg/L for IC II and non-IC II isolates, and was not influenced by addition of 3% bovine serum albumin (BSA); BZT MBC at 30s was 100mg/L without BSA and increased up to 500mg/L upon addition of BSA. No significant differences in BSA were found between DRS and DS isolates. CHX and BZT were effective against Acinetobacter spp. including IC II at a concentration of 1000mg/L and exposure for at least 30s, but their concentrations should be considered carefully to ensure sufficient effects in both clinical and healthcare settings. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  16. Regulatory analysis on the medical use of ephedrine-related products in Taiwan

    Directory of Open Access Journals (Sweden)

    Wan-Nan Yu

    2018-04-01

    Full Text Available To prevent ephedrine-related products from being misused to produce amphetamine and/or its analogs, there's a need for more effective and achievable regulatory mechanisms for the health, police, investigational, prosecution and judiciary authorities in Taiwan. This review was conducted to evaluate the international and Taiwan's regulatory policies and management of medical ephedrine-related products through the corresponding information collected from international and Taiwan government agency authorities. The combat of illegal drugs should involve both supply and demand sides to be successful. Health authorities in Taiwan do not have the investigational power to manage the forbidden transformation, abusing and manufacture of the illegal drugs from ephedrine-related products. Take the judicial interventions in the United States and in Japan as the examples, the organizational cooperation in Taiwan can be one of the main key strategies to combat against illegal drugs from ephedrine-related products. It is necessary to integrate the judicial, police and health agencies to prevent the production of illegal drugs from the ephedrine-related products in Taiwan. The efforts and regulatory control measures should be integrated to speed up the collaboration between different government authorities. It might be achieved through reorganization involving Taiwan Food and Drug Administration. Keywords: Ephedrine-related products, Taiwan Food and Drug Administration (TFDA, Controlled Drugs Act, Pharmaceutical Affairs Act, Pharmacists Act

  17. Certain hormonal profiles of postpartum anestrus jersey crossbred cows treated with controlled internal drug release and ovsynch protocol

    Directory of Open Access Journals (Sweden)

    Dayanidhi Jena

    2016-10-01

    Full Text Available Aim: The study was conducted to determine the serum levels of certain hormones in post-partum anestrus cows following treatment with controlled internal drug release (CIDR and Ovsynch protocol. Materials and Methods: A total of 30 postpartum anestrus cows were divided into three equal groups after thorough gynecoclinical examination. The Group 1 animals received an intravaginal progesterone device on day 0 and 2 ml of prostaglandin F2α (PGF2α on day of CIDR removal (7th day, Group 2 cows were treated with ovsynch protocol (gonadotropinreleasing hormone [GnRH]-PGF2α-GnRH on day 0, 7 and 9, respectively, and Group 3 cows were supplemented with mineral mixture and treated as control. The serum estrogen, progesterone, triiodothyronine, and thyroxine concentration were estimated using enzyme-linked immunosorbent assay kit and absorbance was read at 450 nm with Perkin Elmer Wallac 1420 Microplate Reader. Results: There was a significant increase in progesterone level in Group 1 after withdrawal of CIDR as compared to other two groups. However, the estrogen assay revealed a greater concentration in Group 2 against Group 1 on day 7 of sampling. However, there was no significant difference for serum triiodothyronine (T3 and thyroxine (T4 irrespective of treatment protocols and days of sampling. Conclusion: Treatment with CIDR based progesterone therapy and drug combinations may affect the reproductive hormonal balance like estrogen and progesterone, which is inevitable for successful return to cyclicity and subsequent fertilization and conception. However, as far as serum T3 and T4 concentration concerned it may not give an astounding result.

  18. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2012-01-01

    This section gathers the following national legislative and regulatory activities sorted by country: Bulgaria: General legislation; Czech Republic: General legislation; France: General legislation, Regulatory infrastructure and activity; Germany: General legislation; India: Liability and compensation, Organisation and structure; Ireland: Radiation protection, General legislation; Korea (Republic of): Organisation and structure; Lithuania: Regulatory infrastructure and activity, Radioactive waste management, Radiation protection, international cooperation, Nuclear safety; Poland: General legislation; Romania: Environmental protection; Russian Federation: Radioactive waste management; Slovenia: Nuclear safety; Spain: Liability and compensation, Nuclear security; Sweden: Nuclear safety; Turkey: Radiation protection, Regulatory infrastructure and activity, Nuclear safety, Liability and compensation; United States: General legislation

  19. Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric Acute Lymphocytic Leukemia (ALL): Review from an International Consensus Conference

    NARCIS (Netherlands)

    T.M. Horton (Terzah); R. Sposto (Richard); P. Brown (Patrick); C.P. Reynolds (Patrick); S.P. Hunger (Stephen); N.J. Winick (Naomi); E.A. Raetz (Elizabeth); W.L. Carroll (William); R.J. Arceci (Robert); M.J. Borowitz (Michael); P.S. Gaynon (Paul); L. Gore (Lia); S. Jeha (Sima); B.J. Maurer (Barry); S.E. Siegel (Stuart); A. Biondi (Andrea); P. Kearns (Pamela); A. Narendran (Aru); L.B. Silverman (Lewis); M.A. Smith (Malcolm); C.M. Zwaan (Christian Michel); J.A. Whitlock (James)

    2010-01-01

    textabstractOne of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute

  20. International patenting in ophthalmology: An analysis of its structure and relevance for the development of drugs and diagnostics

    Directory of Open Access Journals (Sweden)

    Hermann AM Mucke

    2008-10-01

    Full Text Available Hermann AM Mucke, Peter Mucke, Eva MuckeHM Pharma Consultancy, Vienna, AustriaAbstract: While investigative ophthalmologists access peer-reviewed journals as part of their daily routine, and while they regularly visit scientific congresses, they rarely peruse patent documents as an information source. Among the reasons for this negligence are the incompatibility of patent search algorithms with those known from journal databases, a legalistic and frequently redundant language, and misconceptions about the nature of the patenting system. Here we present key data and analyses from the ophthalmology module of a patent database system that we are developing to address some of these problems. We show that international patent applications consistently reflect developer interest in the ocular drug and diagnostics field; that they are technically focused lead indicators of developments that frequently feature in peer-reviewed patenting only much later; and that patenting targets are well aligned with the unmet therapeutic needs of populations in industrialized countries. Most applications (74%–78% in years since 2006 are supported with experimental data, and most (on average, 80%–90% faced at least one objection to patentability during their initial stage of examination. In contrast to the peer-reviewed scenery that is highly diverse, the corresponding patenting arena shows a pronounced focus on the United States.Keywords: ophthalmology, eye diseases, iontophoresis, intellectual property, patents as topic, bibliographic databases

  1. Virginia Power's regulatory reduction program

    International Nuclear Information System (INIS)

    Miller, G.D.

    1996-01-01

    Virginia Power has two nuclear plants, North Anna and Surry Power Stations, which have two units each for a total of four nuclear units. In 1992, the Nuclear Regulatory Commission solicited comments from the nuclear industry to obtain their ideas for reducing the regulatory burden on nuclear facilities. Pursuant to the new regulatory climate, Virginia Power developed an internal program to evaluate and assess the regulatory and self-imposed requirements to which they were committed, and to pursue regulatory relief or internal changes where possible and appropriate. The criteria were that public safety must be maintained, and savings must be significant. Up to the date of the conference, over US$22 million of one-time saving had been effected, and US$2.75 million in annual savings

  2. Drug evaluation and the permissive principle: continuities and contradictions between standards and practices in antidepressant regulation.

    Science.gov (United States)

    Abraham, John; Davis, Courtney

    2009-08-01

    Pharmaceuticals are not permitted on to the market unless they are granted regulatory approval. The regulatory process is, therefore, crucial in whether or not a drug is widely prescribed. Regulatory agencies have developed standards of performance that pharmaceuticals are supposed to meet before entering the market. Regulation of technologies is often discussed by reference to the precautionary principle. In contrast, this paper develops the concept of the 'permissive principle' as a way of understanding the departure of regulators' practices from standards of drug efficacy to which regulatory agencies themselves subscribe. By taking a case study of antidepressant regulation in the UK and the USA, the mechanisms of permissive regulatory practices are examined. An STS methodology of both spatial (international) and temporal comparisons of regulatory practices with regulatory standards is employed to identify the nature and extent of the permissive regulation. It is found that the permissive principle was adopted by drug regulators in the UK and the USA, but more so by the former than the latter. Evidently, permissive regulation, which favours the commercial interests of the drug manufacturer, but is contrary to the interests of patients, may penetrate to the heart of regulatory science. On the other hand, permissive regulation of specific drugs should not be regarded as an inevitable result of marketing strategies and concomitant networks deployed by powerful pharmaceutical companies, because the extent of permissive regulation may vary according to the intra-institutional normative commitments of regulators to uphold their technical standards against the commercial interests of the manufacturer. Likely sociological factors that can account for such permissive regulatory practices are 'corporate bias', secrecy and excessive regulatory trust in the pharmaceutical industry in the UK, political expediency and ideological capture in the USA, combined in both countries

  3. Nuclear Regulatory Legislation

    International Nuclear Information System (INIS)

    1989-08-01

    This compilation of statutes and material pertaining to nuclear regulatory legislation through the 100th Congress, 2nd Session, has been prepared by the Office of the General Counsel, US Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document. Persons using this document are placed on notice that it may not be used as an authoritative citation in lieu of the primary legislative sources. Furthermore, while every effort has been made to ensure the completeness and accuracy of this material, neither the United States Government, the Nuclear Regulatory Commission, nor any of their employees makes any expressed or implied warranty or assumes liability for the accuracy or completeness of the material presented in this compilation

  4. Study of the main regulatory mechanisms to encourage renewable and alternative energy applied internationally and in Brazil; Estudo dos principais mecanismos regulatorios de incentivo as fontes renovaveis e alternativas de energia aplicados internacionalmente e no Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Juliana M.C.; Cavaliero, Carla Kazue Nakao [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Fac. de Engenharia Mecanica. Dept. de Energia], Emails: jumcm@fem.unicamp.br, cavaliero@fem.unicamp.br

    2009-07-01

    The investment in renewable and alternative energy sources has been stimulated by some countries in Europe and Americas through the introduction of encouragement regulatory mechanisms. This paper considers the most important international mechanisms such as Feed-in System, Tender System and Quota System with green certificates. In Brazil, there are three regulatory mechanisms in course: PROINFA, the 1. Tender of Renewable and 1. Tender Reserve. The carried out preliminary analysis made possible to classify PROINFA as a mechanism similar to Feed-in, while the auction of Renewable and Reserve are more like an auction system. This article points out the differences and similarities between the instruments and gives a preliminary analysis of their effectiveness, emphasizing national mechanisms, especially regarding the criteria for capacity increase and cost reduction of the technological bands, such as for biomass and small hydroelectric. (author)

  5. The core to regulatory reform

    International Nuclear Information System (INIS)

    Partridge, J.W. Jr.

    1993-01-01

    Federal Energy Regulatory Commission (FERC) Orders 436, 500, and 636, the Clean Air Act Amendments of 1990, Public Utility Holding Company Act reform, and the 1992 Energy Policy Act all can have significant effects on an LDC's operations. Such changes in an LDC's environments must be balanced by changes within the utility, its marketplace, and its state regulatory environment. The question is where to start. For Columbia Gas Distribution Cos., based in Columbus, OH, the new operating foundation begins with each employee. Internal strength is critical in designing initiatives that meet the needs of the marketplace and are well-received by regulators. Employees must understand not only the regulatory environment in which the LDC operates, but also how their work contributes to a positive regulatory relationship. To achieve this, Columbia initiated the COntinuing Regulatory Education program, or CORE, in 1991. CORE is a regulatory-focused, information-initiative program coordinated by Columbia's Regulatory Policy, Planning, and Government Affairs Department. The CORE programs can take many forms, such as emerging issue discussions, dialogues with regulators and key parties, updates on regulatory fillings, regulatory policy meetings, and formal training classes. The speakers and discussion facilitators can range from human resource department trainers to senior officers, from regulatory department staff members to external experts, or from state commissioners to executives from other LDCs. The goals of CORE initiatives are to: Support a professional level of regulatory expertise through employee participation in well-developed regulatory programs presented by credible experts. Encourage a constructive state regulatory environment founded on communication and cooperation. CORE achieves these goals via five program levels: introductory basics, advanced learning, professional expertise, crossfunctional dialogues, and external idea exchanges

  6. Variation in adverse drug reactions listed in product information for antidepressants and anticonvulsants, between the USA and Europe: a comparison review of paired regulatory documents.

    Science.gov (United States)

    Cornelius, Victoria R; Liu, Kun; Peacock, Janet; Sauzet, Odile

    2016-03-20

    To compare consistency of adverse drug reaction (ADR) data in publicly available product information documents for brand drugs, between the USA and Europe. To assess the usefulness of information for prescribers and patients. A comparison review of product information documents for antidepressants and anticonvulsants concurrently marketed by the same pharmaceutical company in the USA and Europe. For each drug, data were extracted from the US Product Inserts and the European Summary of Product Characteristics documents between 09/2013 and 01/2015. Individuals contributing ADR information to product information documents. All ADRs reported in product information sections 5 and 6 (USA), and 4·4 and 4·8 (Europe). Twelve brand drugs--24 paired documents--were included. On average, there were 77 more ADRs reported in the USA compared with in the European product information document, with a median number of 201 ADRs (range: 65-425) and 114 (range: 56-265), respectively. More product information documents in the USA reported information on the source of evidence (10 vs 5) and risk (9 vs 5) for greater than 80% of ADRs included in the document. There was negligible information included regarding duration, severity, reversibility or recurrence of ADRs. On average, only 29% of ADR terms were reported in both paired documents. Product information documents contained a large number of ADRs, but lacked contextual data and information important to patients and prescribers, such as duration, severity and reversibility. The ADR profile was found to be inconsistently reported between the USA and Europe, for the same drug. Identifying, selecting, summarising and presenting multidimensional harm data should be underpinned by practical evidence-based guidelines. In order for prescribers to provide considered risk-benefit advice across competing drug therapies to patients, they need access to comprehensible and reliable ADR information. Published by the BMJ Publishing Group Limited

  7. International

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    This rubric reports on 10 short notes about international economical facts about nuclear power: Electricite de France (EdF) and its assistance and management contracts with Eastern Europe countries (Poland, Hungary, Bulgaria); Transnuclear Inc. company (a 100% Cogema daughter company) acquired the US Vectra Technologies company; the construction of the Khumo nuclear power plant in Northern Korea plays in favour of the reconciliation between Northern and Southern Korea; the delivery of two VVER 1000 Russian reactors to China; the enforcement of the cooperation agreement between Euratom and Argentina; Japan requested for the financing of a Russian fast breeder reactor; Russia has planned to sell a floating barge-type nuclear power plant to Indonesia; the control of the Swedish reactor vessels of Sydkraft AB company committed to Tractebel (Belgium); the renewal of the nuclear cooperation agreement between Swiss and USA; the call for bids from the Turkish TEAS electric power company for the building of the Akkuyu nuclear power plant answered by three candidates: Atomic Energy of Canada Limited (AECL), Westinghouse (US) and the French-German NPI company. (J.S.)

  8. Characterization of endocrine events during the periestrous period in sheep after estrous synchronization with controlled internal drug release (CIDR) device.

    Science.gov (United States)

    Van Cleeff, J; Karsch, F J; Padmanabhan, V

    1998-01-01

    The Controlled Internal Drug Releasing (CIDR) device is an intravaginal pessary containing progesterone (P4) designed for synchronizing estrus in ruminants. To date, there has been little information available on the timing, duration, and quality of the follicular phase after CIDR removal and how those characteristics compare with natural periovulatory endocrine events. The present communication relates the results of methods we used to characterize the endocrine events that followed CIDR synchronization. Breeding-season ewes were given an injection (10 mg) of Lutalyse (PGF2 alpha), and then studied during three consecutive estrous cycles, beginning in the luteal phase after the estrus induced by PGF2 alpha. Cycle 1 estrus was synchronized with 1 CIDR (Type G) inserted for 8 d beginning 10 d after PGF2 alpha. Cycles 2 and 3 were synchronized with two CIDRs for 8 d beginning 10 d after previous CIDR removal. Cycle 1 estrous behavior and serum gonadotropins showed a follicular phase (the interval from CIDR withdrawal to gonadotropin surge [surge] peak) of 38.2 +/- 1.5 hr. Two CIDRs lengthened the interval to 46.2 +/- 1.5 hr (P synchronization concentrated surges within a 24-hr period in 92% of the ewes in Cycles 1 and 2. Cycles 3 ewes were euthanized at estimated luteal, early follicular, late follicular, LH surge, and secondary FSH rise timepoints. Endocrine data and ovaries showed that 88% of the ewes synchronized with two CIDRs were in the predicted stage of the estrous cycle. These data demonstrate that the CIDR device applied during the luteal phase effectively synchronizes estrus and results in a CIDR removal-to-surge interval of similar length to a natural follicular phase.

  9. Controlled breeding and reproductive management in water buffaloes (Bubalus bubalis) using Eazi Breed controlled internal drug release.

    Science.gov (United States)

    Hiremath, Shivayogi; Ramesha, Kerekoppa P

    2015-06-04

    Buffalo reproduction is considerably affected by late maturity, poor oestrus symptoms and long postpartum periods. This study was undertaken to evaluate the efficiency of Eazi Breed controlled internal drug release (CIDR), an intravaginal progesterone-releasing device, in relation to oestrus and fertility. Five hundred true anoestrus buffalo cows, in the age group 4-6 years in 10 villages of Dharwad district in Karnataka state in India, were randomly selected and treated with CIDR for 9 days. Two mL of Cidirol (1 mg oestradiol benzoate) was administered intramuscularly to all animals on day 10. Forty-two buffaloes (8.4%) that failed to show oestrus signs (1.6%) or showed weak signs of oestrus (6.8%) after the first treatment were treated again 72 h after the Cidriol injection with a new device, and inseminated after the expression of oestrus. After the second treatment all the animals showed oestrus signs. The percentage of buffaloes showing intense oestrus was 67.40%, intermediate oestrus was shown by 25.80%, whilst 6.80% buffaloes showed weak oestrus even after the second treatment. The buffaloes showing oestrus signs were inseminated twice with an interval of 12 h, starting 12 h after the start of the oestrus signs. In 86 buffaloes showing prolonged oestrus signs a third insemination was done. The conception rates were 85.16%, 60.47% and 44.11% respectively in buffaloes showing intense, intermediate and weak oestrus. Transrectal palpation of the genital tract was performed 45-60 days post-insemination to diagnose pregnancy status, and in doubtful cases pregnancy was reconfirmed at 90 days after insemination. Out of 500 buffaloes treated in this way 380 animals became pregnant and the pregnancy rate was 76%. This study revealed the usefulness of Eazi Breed CIDR along with Cidirol treatment in buffaloes to improve their reproductive performance.

  10. Controlled breeding and reproductive management in water buffaloes (Bubalus bubalis using Eazi Breed controlled internal drug release

    Directory of Open Access Journals (Sweden)

    Shivayogi Hiremath

    2015-06-01

    Full Text Available Buffalo reproduction is considerably affected by late maturity, poor oestrus symptoms and long postpartum periods. This study was undertaken to evaluate the efficiency of Eazi Breed controlled internal drug release (CIDR, an intravaginal progesterone-releasing device, in relation to oestrus and fertility. Five hundred true anoestrus buffalo cows, in the age group 4–6 years in 10 villages of Dharwad district in Karnataka state in India, were randomly selected and treated with CIDR for 9 days. Two mL of Cidirol (1 mg oestradiol benzoate was administered intramuscularly to all animals on day 10. Forty-two buffaloes (8.4% that failed to show oestrus signs (1.6% or showed weak signs of oestrus (6.8% after the first treatment were treated again 72 h after the Cidriol injection with a new device, and inseminated after the expression of oestrus. After the second treatment all the animals showed oestrus signs. The percentage of buffaloes showing intense oestrus was 67.40%, intermediate oestrus was shown by 25.80%, whilst 6.80% buffaloes showed weak oestrus even after the second treatment. The buffaloes showing oestrus signs were inseminated twice with an interval of 12 h, starting 12 h after the start of the oestrus signs. In 86 buffaloes showing prolonged oestrus signs a third insemination was done. The conception rates were 85.16%, 60.47% and 44.11% respectively in buffaloes showing intense, intermediate and weak oestrus. Transrectal palpation of the genital tract was performed 45–60 days post-insemination to diagnose pregnancy status, and in doubtful cases pregnancy was reconfirmed at 90 days after insemination. Out of 500 buffaloes treated in this way 380 animals became pregnant and the pregnancy rate was 76%. This study revealed the usefulness of Eazi Breed CIDR along with Cidirol treatment in buffaloes to improve their reproductive performance.

  11. Nuclear regulatory decision making

    International Nuclear Information System (INIS)

    Wieland, Patricia; Almeida, Ivan Pedro Salati de

    2011-01-01

    The scientific considerations upon which the nuclear regulations are based provide objective criteria for decisions on nuclear safety matters. However, the decisions that a regulatory agency takes go far beyond granting or not an operating license based on assessment of compliance. It may involve decisions about hiring experts or research, appeals, responses to other government agencies, international agreements, etc.. In all cases, top management of the regulatory agency should hear and decide the best balance between the benefits of regulatory action and undue risks and other associated impacts that may arise, including issues of credibility and reputation. The establishment of a decision framework based on well established principles and criteria ensures performance stability and consistency, preventing individual subjectivity. This article analyzes the challenges to the decision-making by regulatory agencies to ensure coherence and consistency in decisions, even in situations where there is uncertainty, lack of reliable information and even divergence of opinions among experts. The article explores the basic elements for a framework for regulatory decision-making. (author)

  12. Communication Received from the Permanent Mission of Pakistan to the International Atomic Energy Agency Concerning the Promulgation of the Pakistan Nuclear Regulatory Authority Ordinance 2001

    International Nuclear Information System (INIS)

    2001-01-01

    The Director General has received a communication dated 30 January 2001 from the Permanent Mission of Pakistan forwarding a press release concerning the promulgation of the Pakistan Nuclear Regulatory Authority Ordinance 2001. As requested in that communication, the press release is attached hereto for the information of Member States

  13. Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects : Current knowledge assembled at an international workshop at BfR, Germany

    DEFF Research Database (Denmark)

    Peiser, M; Tralau, T; Heidler, J

    2012-01-01

    potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed....

  14. [Adaptations of psychotropic drugs in patients aged 75 years and older in a departement of geriatric internal medecine: report of 100 cases].

    Science.gov (United States)

    Couderc, Anne-Laure; Bailly-Agaledes, Cindy; Camalet, Joëlle; Capriz-Ribière, Françoise; Gary, André; Robert, Philippe; Brocker, Patrice; Guérin, Olivier

    2011-06-01

    The elderly often with multiple diseases are particularly at risk from adverse drug reactions. Nearly half of iatrogenic drug in the elderly are preventable. Some medications such as psychotropic drugs are particularly involved in iatrogenic accidents. We wanted to know if the tools of the comprehensive geriatric assessment or other factors could influence the changes of psychotropic drugs in a geriatric departement. Our prospective study of four months in 100 patients aged 75 years and older hospitalized in the Geriatric Internal Medecine Departement of University Hospital of Nice investigated what were the clinical or biological reasons and tools used during changes of psychotropic drugs. We compared these changes according to the comprehensive geriatric assessment tools and we analyzed the changes based on lists of potentially inappropriate medications by Laroche et al. and from the instrument STOPP/START. The Mini Mental State Examination (MMSE) was the tool that has most influenced the changes in psychotropic including a tendency to increase and the introduction of anxiolytics when MMSE < 20 (p = 0.007) while neuroleptics instead arrested and decreased (p = 0.012). The comprehensive geriatric assessment has its place in decision support during the potentially iatrogenic prescriptions of drugs such as psychotropic and new tools such as STOPP/START can also be a help to the prescriber informed.

  15. Regulatory challenges associated with conducting multicountry clinical trials in resource-limited settings.

    Science.gov (United States)

    Ndebele, Paul; Blanchard-Horan, Christina; Shahkolahi, Akbar; Sanne, Ian

    2014-01-01

    International public health and infectious diseases research has expanded to become a global enterprise transcending national and continental borders in organized networks addressing high-impact diseases. In conducting multicountry clinical trials, sponsors and investigators have to ensure that they meet regulatory requirements in all countries in which the clinical trials will be conducted. Some of these requirements include review and approval by national drug regulatory authorities and recognized research ethics committees. A limiting factor to the efficient conduct of multicountry clinical trials is the regulatory environment in each collaborating country, with significant differences determined by various factors including the laws and the procedures used in each country. The long regulatory processes in resource-limited countries may hinder the efficient implementation of multisite clinical trials, delaying research important to the health of populations in these countries and costing millions of dollars a year.

  16. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2014-01-01

    This section of the Bulletin presents a summary of the recent national legislative and regulatory activities sorted by country and topic: - Algeria: Nuclear security. - France: Radioactive waste management; Nuclear safety and radiological protection; General legislation; International co-operation. - Germany: International trade. - Indonesia: Nuclear security, General legislation. - Ireland: Nuclear safety and radiological protection; General legislation. - Lithuania: Nuclear security; Nuclear safety and radiological protection. - Slovak Republic: International co-operation; Liability and compensation; Environmental protection. - Switzerland: Radioactive waste management. - United Arab Emirates: Liability and compensation. - United States: Radioactive waste management; Licensing and regulatory infrastructure

  17. German Kava Ban Lifted by Court: The Alleged Hepatotoxicity of Kava (Piper methysticum) as a Case of Ill-Defined Herbal Drug Identity, Lacking Quality Control, and Misguided Regulatory Politics.

    Science.gov (United States)

    Kuchta, Kenny; Schmidt, Mathias; Nahrstedt, Adolf

    2015-12-01

    Kava, the rhizome and roots of Piper methysticum, are one of the most important social pillars of Melanesian societies. They have been used for more than 1000 years in social gatherings for the preparation of beverages with relaxing effects. During the colonial period, extract preparations found their way into Western medicinal systems, with experience especially concerning the treatment of situational anxiety dating back more than 100 years. It therefore came as a surprise when the safety of kava was suddenly questioned based on the observation of a series of case reports of liver toxicity in 1999 and 2000. These case reports ultimately led to a ban of kava products in Europe - a ban that has been contested because of the poor evidence of risks related to kava. Only recently, two German administrative courts decided that the decision of the regulatory authority to ban kava as a measure to ensure consumer safety was inappropriate and even associated with an increased risk due to the higher risk inherent to the therapeutic alternatives. This ruling can be considered as final for at least the German market, as no further appeal has been pursued by the regulatory authorities. However, in order to prevent further misunderstandings, especially in other markets, the current situation calls for a comprehensive presentation of the cardinal facts and misconceptions concerning kava and related drug quality issues. Georg Thieme Verlag KG Stuttgart · New York.

  18. Regulatory Oversight of Cell and Gene Therapy Products in Canada.

    Science.gov (United States)

    Ridgway, Anthony; Agbanyo, Francisca; Wang, Jian; Rosu-Myles, Michael

    2015-01-01

    Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTPs) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTPs, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonisation at an international level are essential for progress in the development and commercialisation of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking.

  19. Effect of drug law enforcement on drug market violence: a systematic review.

    Science.gov (United States)

    Werb, Dan; Rowell, Greg; Guyatt, Gordon; Kerr, Thomas; Montaner, Julio; Wood, Evan

    2011-03-01

    Violence is amongst the primary concerns of communities around the world and research has demonstrated links between violence and the illicit drug trade, particularly in urban settings. Given the growing emphasis on evidence-based policy-making, and the ongoing severe drug market violence in Mexico and other settings, we conducted a systematic review to examine the impacts of drug law enforcement on drug market violence. We conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Specifically, we undertook a search of English language electronic databases (Academic Search Complete, PubMed, PsycINFO, EMBASE, Web of Science, Sociological Abstracts, Social Service Abstracts, PAIS International and Lexis-Nexis), the Internet (Google, Google Scholar), and article reference lists, from database inception to January 24, 2011. Overall, 15 studies were identified that evaluated the impact of drug law enforcement on drug market violence, including 11 (73%) longitudinal analyses using linear regression, 2 (13%) mathematical drug market models, and 2 (13%) qualitative studies. Fourteen (93%) studies reported an adverse impact of drug law enforcement on levels of violence. Ten of the 11 (91%) studies employing longitudinal qualitative analyses found a significant association between drug law enforcement and drug market violence. Our findings suggest that increasing drug law enforcement is unlikely to reduce drug market violence. Instead, the existing evidence base suggests that gun violence and high homicide rates may be an inevitable consequence of drug prohibition and that disrupting drug markets can paradoxically increase violence. In this context, and since drug prohibition has not meaningfully reduced drug supply, alternative regulatory models will be required if drug supply and drug market violence are to be meaningfully reduced. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. 21 CFR 312.86 - Focused FDA regulatory research.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Focused FDA regulatory research. 312.86 Section 312.86 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency...

  1. QT interval correction for drug-induced changes in body temperature during integrated cardiovascular safety assessment in regulatory toxicology studies in dogs: A case study.

    Science.gov (United States)

    El Amrani, Abdel-Ilah; El Amrani-Callens, Francine; Loriot, Stéphane; Singh, Pramila; Forster, Roy

    2016-01-01

    Cardiovascular safety assessment requires accurate evaluation of QT interval, which depends on the length of the cardiac cycle and also on core body temperature (BT). Increases in QT interval duration have been shown to be associated with decreases in BT in dogs. An example of altered QT interval duration associated with changes in body temperature observed during a 4-week regulatory toxicology study in dogs is presented. Four groups of Beagle dogs received the vehicle or test item once on Day 1, followed by a 4-week observation period. Electrocardiogram (ECG) parameters were continuously recorded on Days 1 and 26 by jacketed external telemetry (JET). Core body temperature (BT) was measured with a conventional rectal thermometer at appropriate time-points during the Day 1 recording period. Decreased BT was observed approximately 2h after treatment on Day 1, along with increased QT interval duration corrected according to the Van de Water formula (QTcV), but the effect was no longer observed after correction for changes in BT [QTcVcT=QTcV-14(37.5-BT)] according to the Van der Linde formula. No significant changes in QTcV were reported at the end of the observation period, on Day 26. The present study demonstrates that core body (rectal) temperature can easily be monitored at appropriate time-points during JET recording in regulatory toxicology studies in dogs, in order to correct QT interval duration values for treatment-related changes in BT. The successful application of the Van der Linde formula to correct QTc prolongation for changes in BT was demonstrated. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  3. Data Management in a Regulatory Context

    Directory of Open Access Journals (Sweden)

    Niels Grønning

    2017-07-01

    Full Text Available With the implementation of Article 57(2 in 2012 the European Medicines Agency (EMA embarked on a digitalization journey that foreseeably would ensure greater product oversight and interoperability across the community. This initiative has subsequently led to additional focus from the agency with respect to the utilization and harmonization of data as part of the regulatory process. Driven by both internal and external factors, the EMA have through the European Union telematics strategy laid the foundation for the regulatory-driven services that may be expected from the community the coming years. Supported by standardization initiatives (e.g., ISO Identification of Medicinal Products, the EMA is gradually building an information management-driven approach to data utilization and exploitation within drug evaluation and approval. Primarily driven by the increasing demand for signal detection, the EMA is additionally hoping to leverage the establishment of defined information models and supporting controlled terms to safeguard future activities within the community. Collectively, the overall community may seek to gain from the overall digitalization roadmap proposed by the EMA and interesting opportunities may be sought as part of the transition. Already now pharmaceutical companies are gradually adapting to this new paradigm and actively seeking to explore how they may leverage the future EMA operating model to serve internal business requirements. If successful, the collective efforts from industry and regulators may lead to an unprecedented product oversight and offer regulators the opportunity to proactively drive corrective actions and, therefore, improve patient safety.

  4. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2016-01-01

    This section treats of the following National legislative and regulatory activities: 1 - France: General legislation, regulations and instruments; Nuclear trade (including non-proliferation); International co-operation; 2 - India: Licensing and regulatory infrastructure; Liability and compensation; 3 - Ireland: Nuclear safety and radiological protection (including nuclear emergency planning); Transport of radioactive material; Nuclear trade (including non-proliferation); 4 - Lithuania: Licensing and regulatory infrastructure; Nuclear safety and radiological protection (including nuclear emergency planning); Radioactive waste management; 5 - Luxembourg: Nuclear safety and radiological protection (including nuclear emergency planning); 6 - Slovak Republic: International co-operation; General legislation, regulations and instruments; 7 - Spain: Radioactive materials (including physical protection); Radioactive waste management; 8 - United States: Licensing and regulatory infrastructure

  5. Retail prices of essential drugs in Brazil: an international comparison Precios minoristas de medicamentos esenciales en Brasil: comparación internacional

    Directory of Open Access Journals (Sweden)

    Otávio de Tolêdo Nóbrega

    2007-08-01

    Full Text Available OBJECTIVES: Price is a key obstacle for consumer access to essential drugs, especially in developing countries. This study sought to compare the retail prices of essential drugs on the private market in Brazil with that of two international pricing standards. METHODS: The retail price of all drugs on Brazil's Essential Drugs List, July 2000 edition, were compared to the retail price of the same drugs on the Swedish market and on a referential bulk-price indicator from low-cost suppliers on the international market. Ratios of Brazil's prices to Sweden's prices and Brazil's prices to the international bulk mean price-per-unit for each drug were calculated. Using linear regression analysis, the ratios were also studied in relation to the number of manufacturers. RESULTS: For the 132 drugs that were listed on both Brazil's and Sweden's lists, unitary retail prices in Brazil were 1.9 times higher. Of the 94 drugs found on both Brazil's list and the international unit-price indicator, Brazil's national mean unit prices were 13.1 more expensive. No relationship was found between the number of manufacturers for each product and the ratios of prices. CONCLUSIONS: Average retail prices of essential drugs in Brazil are significantly higher than in Sweden. Furthermore, international bulk prices indicate that drugs are brought to market by Brazil's private pharmacies at prices that may be excessively high in relation to production costs, creating high profit margins. The expected price-lowering effects of competition were not identified.OBJETIVO: Los precios constituyen un obstáculo clave para el acceso del consumidor a los medicamentos esenciales, especialmente en los países en desarrollo. El objetivo de este estudio fue comparar los precios minoristas de los medicamentos esenciales en el mercado privado de Brasil con los de dos estándares internacionales de precios. MÉTHODS: Se compararon los precios minoristas de todos los medicamentos de la Lista de

  6. Patient Preferences in Regulatory Benefit-Risk Assessments: A US Perspective.

    Science.gov (United States)

    Johnson, F Reed; Zhou, Mo

    Demands for greater transparency in US regulatory assessments of benefits and risks, together with growing interest in engaging patients in Food and Drug Administration regulatory decision making, have resulted in several recent regulatory developments. Although Food and Drug Administration's Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiological Health (CDRH) have established patient-engagement initiatives, CDRH has proposed guidelines for considering quantitative data on patients' benefit-risk perspectives, while CDER has focused on a more qualitative approach. We summarize two significant studies that were developed in collaboration and consultation with CDER and CDRH. CDER encouraged a patient advocacy group to propose draft guidance on engaging patient and caregiver stakeholders in regulatory decision making for Duchenne muscular dystrophy. CDRH sponsored a discrete-choice experiment case study to quantify obese respondents' perspectives on "meaningful benefits." CDRH and CDER issued draft guidance in May and June 2015, respectively, on including patient-preference data in regulatory submissions. Both organizations face challenges. CDER is working on integrating qualitative data into existing evidence-based review processes and is exploring options for therapeutic areas not included on a priority list. CDRH has adopted an approach that requires patient-preference data to satisfy standards of valid scientific evidence. Although that strategy could facilitate integrating patient perspectives directly with clinical data on benefits and harms, generating such data requires building capacity. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  7. Nuclear regulatory developments in Canada

    International Nuclear Information System (INIS)

    Binder, M.

    2012-01-01

    This paper from CNSC discusses nuclear regulatory developments in Canada. It starts with the Fukushima accident and the effect on the nuclear sector. It summarises what CNSC has done, what it has learned and their plans going forward. It has made recommendations to IAEA for international enhancements to regulatory procedures. It outline the activities of Canada's nuclear power plants, Canada's uranium projects, deep geological repository and waste management as well as nuclear research in Canada.

  8. Regulatory facility guide for Ohio

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, S.S.; Bock, R.E.; Francis, M.W.; Gove, R.M.; Johnson, P.E.; Kovac, F.M.; Mynatt, J.O. [Oak Ridge National Lab., TN (United States); Rymer, A.C. [Transportation Consulting Services, Knoxville, TN (United States)

    1994-02-28

    The Regulatory Facility Guide (RFG) has been developed for the DOE and contractor facilities located in the state of Ohio. It provides detailed compilations of international, federal, and state transportation-related regulations applicable to shipments originating at destined to Ohio facilities. This RFG was developed as an additional resource tool for use both by traffic managers who must ensure that transportation operations are in full compliance with all applicable regulatory requirements and by oversight personnel who must verify compliance activities.

  9. Assessment of regulatory effectiveness. Peer discussions on regulatory practices

    International Nuclear Information System (INIS)

    1999-09-01

    This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

  10. SAFE USE OF DRUGS DURING PREGNANCY IN FOCUS OF INTERNATIONAL PRACTICE OF PHARMACOVIGILANCE SYSTEM AND TERATOLOGICAL INFORMATION SERVICE ORGANIZATION

    Directory of Open Access Journals (Sweden)

    K. A. Lutsevich

    2012-01-01

    Full Text Available The safe use of drugs during pregnancy is essential to optimize the health of both pregnant woman and her future child. At the same time obstetrician-gynecologists often face the lack of evidence-based information on the use of drugs and leave the issue to the woman herself — whether the treatment benefit to the mother outweighs risks to the unborn child — relying on the limited amount of scientific data. Preconception discussion of actual risks and safe treatment reduces patient fears and maximizes the emphasis on the therapy safety. At the same time, the lack of adequate information on safety for the majority of drugs used by pregnant women combined with the need to make appropriate treatment decisions and communicate drug risk information to a potentially vulnerable population is the most challenging and critical issue of pregnant women's health.

  11. Pediatric Melanoma and Drug Development

    Directory of Open Access Journals (Sweden)

    Klaus Rose

    2018-03-01

    Full Text Available Importance—Pediatric melanoma occurs, albeit rarely. Should patients be treated by today’s medical standards, or be subjected to medically unnecessary clinical studies? Observations—We identified international, industry-sponsored pediatric melanoma studies triggered by regulatory demands in www.clinicaltrials.gov and further pediatric melanoma studies demanded by European Union pediatric investigation plans. We retrieved related regulatory documents from the internet. We analyzed these studies for rationale and medical beneficence on the basis of physiology, pediatric clinical pharmacology and rationale. Regulatory authorities define children by chronological age, not physiologically. Newborns’ organs are immature but they develop and mature rapidly. Separate proof of efficacy in underage patients is justified formally/regulatorily but lacks medical sense. Children—especially post-puberty—and adults vis-a-vis medications are physiologically very similar. Two adolescent melanoma studies were terminated in 2016 because of waning recruitment, while five studies in pediatric melanoma and other solid tumors, triggered by European Union pediatric investigation plans, continue recruiting worldwide. Conclusions and Relevance—Regulatory-demanded pediatric melanoma studies are medically superfluous. Melanoma patients of all ages should be treated with effective combination treatment. Babies need special attention. Children need dose-finding and pharmacokinetic studies but adolescents metabolize and respond to drugs similarly to adults. Institutional Review Boards/ethics committees should suspend ongoing questionable pediatric melanoma studies and reject newly submitted questionable studies.

  12. Report on the International Workshop on Drug Prevention and Treatment in Rural Settings Organized by United Nation Office on Drugs and Crime (UNODC) and World Health Organization (WHO).

    Science.gov (United States)

    Milano, Giulia; Saenz, Elizabeth; Clark, Nicolas; Busse, Anja; Gale, John; Campello, Giovanna; Mattfeld, Elizabeth; Maalouf, Wadih; Heikkila, Hanna; Martelli, Antonietta; Morales, Brian; Gerra, Gilberto

    2017-11-10

    Very little evidence has been reported in literature regarding the misuse of substances in rural areas. Despite the common perception of rural communities as a protective and risk-mitigating environment, the scientific literature demonstrated the existence of many risk factors in rural communities. The Drug Prevention and Health Branch (DHB) of the United Nations Office on Drugs and Crime (UNODC), and the World Health Organization (WHO), in June 2016, organized a meeting of experts in treatment and prevention of SUDs in rural settings. The content presented during the meeting and the related discussion have provided materials for the preparation of an outline document, which is the basis to create a technical tool on SUDs prevention and treatment in rural settings. The UNODC framework for interventions in rural settings is a technical tool aimed to assist policy makers and managers at the national level. This paper is a report on UNODC/WHO efforts to improve the clinical conditions of people affected by SUDs and living in rural areas. The purpose of this article is to draw attention on a severe clinical and social problem in a reality forgotten by everyone.

  13. [Orphan drugs].

    Science.gov (United States)

    Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

    2013-01-01

    Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

  14. Existing nuclear power plants and new safety requirements - an international survey. A description of the legal situation and of the regulatory practice in eight countries and in Germany

    International Nuclear Information System (INIS)

    Raetzke, C.; Micklinghoff, M.

    2006-01-01

    In our days, the question of whether existing nuclear power plants can be expected to comply with new standards is relevant for many reasons. The idea of writing this report was sparked by the fact that the German Federal Ministry of the Environment is planning a thorough revision of the regulations concerning nuclear safety. Since in Germany, according to the latest amendment to the Nuclear Act, a licence for a new plant cannot be granted, this project inevitably raises the basic question of whether the existing plants can be forced to comply with new safety regulation, if necessary by performing substantial backfitting. Aim of the enquiry is to find out how the question outlined above - new requirements for existing nuclear power plants - is dealt with in nine countries, namely Germany, Switzerland, France, Sweden, Finland, the United Kingdom, the USA, Spain and Belgium. In order to give a legible and qualified account, the authors have also investigated and depicted the general legislative and regulatory framework for nuclear of each country. Therefore, the book can also be read as a general introduction into the legal system and regulatory practice of these countries. (orig.)

  15. Nanotechnology and Drug Delivery Part 2: Nanostructures for Drug ...

    African Journals Online (AJOL)

    Some challenges associated with the technology as it relates to drug effectiveness, toxicity, stability, pharmacokinetics and drug regulatory control are discussed in this review. Clearly, nanotechnology is a welcome development that is set to transform drug delivery and drug supply chain management, if optimally developed ...

  16. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2014-01-01

    This section treats of the following activities sorted by country: 1 - Belarus: International cooperation, Organisation and structure, Licensing and regulatory infrastructure, Nuclear safety and radiological protection; 2 - France: Nuclear safety and radiological protection, Radioactive waste management, Environmental protection, Liability and compensation, International co-operation; 3 - Hungary: General legislation, Radioactive waste management, Nuclear security; 4 - Ireland: Nuclear safety and radiological protection (including emergency planning); 5 - Lithuania: Licensing and regulatory infrastructure; 6 - Moldova: Nuclear safety and radiological protection; 7 - Portugal: Radioactive waste management, Nuclear safety and radiological protection; 8 - Slovak Republic: Radioactive waste management, Liability and compensation; 9 - Spain: Radioactive waste management; 10 - Ukraine: Radioactive waste management; 11 - United Kingdom: Organisation and structure

  17. Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

    Science.gov (United States)

    Swedberg, Michael D B

    2016-01-01

    Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit

  18. Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey.

    Science.gov (United States)

    Lawn, Will; Hallak, Jaime E; Crippa, Jose A; Dos Santos, Rafael; Porffy, Lilla; Barratt, Monica J; Ferris, Jason A; Winstock, Adam R; Morgan, Celia J A

    2017-11-09

    Ayahuasca is a natural psychedelic brew, which contains dimethyltryptamine (DMT). Its potential as a psychiatric medicine has recently been demonstrated and its non-medical use around the world appears to be growing. We aimed to investigate well-being and problematic alcohol use in ayahuasca users, and ayahuasca's subjective effects. An online, self-selecting, global survey examining patterns of drug use was conducted in 2015 and 2016 (n = 96,901). Questions were asked about: use of ayahuasca, lysergic acid diethylamide (LSD) and magic mushrooms; demographics, current well-being and past-year problematic alcohol use of past-year ayahuasca users and comparison drug users; and subjective effects of ayahuasca and comparison drugs. Ayahuasca users (n = 527) reported greater well-being than both classic psychedelic users (n = 18,138) and non-psychedelic drug-using respondents (n = 78,236). Ayahuasca users reported less problematic drinking than classic psychedelic users, although both groups reported greater problematic drinking than the other respondents. Ayahuasca's acute subjective effects usually lasted for six hours and were most strongly felt one hour after consumption. Within our online, self-selecting survey, ayahuasca users reported better well-being than comparison groups and less problematic drinking than classic psychedelic users. Future longitudinal studies of international samples and randomised controlled trials are needed to dissect the effects of ayahuasca on these outcomes.

  19. Cumulative exposure to phthalates from phthalate-containing drug products

    DEFF Research Database (Denmark)

    Ennis, Zandra Nymand; Broe, Anne; Pottegård, Anton

    2018-01-01

    European regulatory limit of exposure ranging between 380-1710 mg/year throughout the study period. Lithium-products constituted the majority of dibutyl phthalate exposure. Diethyl phthalate exposure, mainly caused by erythromycin, theophylline and diclofenac products, did not exceed the EMA regulatory...... to quantify annual cumulated phthalate exposure from drug products among users of phthalate-containing oral medications in Denmark throughout the period of 2004-2016. METHODS: We conducted a Danish nationwide cohort study using The Danish National Prescription Registry and an internal database held...

  20. Regulatory aspects of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Kristensen, K.

    1985-01-01

    Regulatory systems in the field of radiopharmaceuticals have two main purposes: efficacy and safety. Efficacy expresses the quality of the diagnostic and therapeutic process for the patient. Safety involves the patient, the staff, and the environment. The world situation regarding regulations for radiopharmaceuticals is reviewed on the basis of a survey in WHO Member States. The main content of such regulations is discussed. The special properties of radiopharmaceuticals compared with ordinary drugs may call for modified regulations. Several countries are preparing such regulations. Close co-operation and good understanding among scientists working in hospital research, industry and regulatory bodies will be of great importance for the fast and safe introduction of new radiopharmaceuticals for the benefit of the patient. Before introducing new legislation in this field, a radiopharmaceutical expert should analyse the situation in the country and the relationship to the existing regulations. It is expected that the most important factor in promoting the fast introduction of new, safe and effective radiopharmaceuticals will be the training of people working within the regulatory bodies. It is foreseen that the IAEA and WHO will have an important role to play by providing expert advice and training in this area. (author)

  1. 21 CFR 201.326 - Over-the-counter drug products containing internal analgesic/antipyretic active ingredients...

    Science.gov (United States)

    2010-04-01

    ... higher if you [bullet] are age 60 or older [bullet] have had stomach ulcers or bleeding problems [bullet... stomach ulcers or bleeding problems [bullet] takes a blood thinning (anticoagulant) or steroid drug... bleeding. The chance is higher if the user [bullet] has had stomach ulcers or bleeding problems [bullet...

  2. International drug price comparisons: quality assessment Comparación internacional de precios de medicamentos: evaluación de la calidad

    Directory of Open Access Journals (Sweden)

    Márcio Machado

    2011-01-01

    Full Text Available OBJECTIVE: To quantitatively summarize results (i.e., prices and affordability reported from international drug price comparison studies and assess their methodological quality. METHODS: A systematic search of the most relevant databases-Medline, Embase, International Pharmaceutical Abstracts (IPA, and Scopus, from their inception to May 2009-was conducted to identify original research comparing international drug prices. International drug price information was extracted and recorded from accepted papers. Affordability was reported as drug prices adjusted for income. Study quality was assessed using six criteria: use of similar countries, use of a representative sample of drugs, selection of specific types of prices, identification of drug packaging, different weights on price indices, and the type of currency conversion used. RESULTS: Of the 1 828 studies identified, 21 were included. Only one study adequately addressed all quality issues. A large variation in study quality was observed due to the many methods used to conduct the drug price comparisons, such as different indices, economic parameters, price types, basket of drugs, and more. Thus, the quality of published studies was considered poor. Results varied across studies, but generally, higher income countries had higher drug prices. However, after adjusting drug prices for affordability, higher income countries had more affordable prices than lower income countries. CONCLUSIONS: Differences between drug prices and affordability in different countries were found. Low income countries reported less affordability of drugs, leaving room for potential problems with drug access, and consequently, a negative impact on health. The quality of the literature on this topic needs improvement.OBJETIVO: Resumir cuantitativamente los resultados (p. ej., precios y asequibilidad presentados en estudios de comparación internacional de precios de medicamentos y evaluar su calidad metodológica. M

  3. What's the Regulatory Value of a Target Product Profile?

    Science.gov (United States)

    Breder, Christopher D; Du, Wenny; Tyndall, Adria

    2017-07-01

    Target product profiles (TPPs) are used as a regulatory tool for dialog on clinical development or manufacturing plans. Drugs and biologics approved by the FDA that mention TPPs are associated with more efficient regulatory review times, perhaps as a result of increased planning or because the TPP promotes well-organized regulatory dialog. Published by Elsevier Ltd.

  4. HER2 monoclonal antibodies that do not interfere with receptor heterodimerization-mediated signaling induce effective internalization and represent valuable components for rational antibody-drug conjugate design.

    Science.gov (United States)

    de Goeij, Bart E C G; Peipp, Matthias; de Haij, Simone; van den Brink, Edward N; Kellner, Christian; Riedl, Thilo; de Jong, Rob; Vink, Tom; Strumane, Kristin; Bleeker, Wim K; Parren, Paul W H I

    2014-01-01

    The human epidermal growth factor receptor (HER)2 provides an excellent target for selective delivery of cytotoxic drugs to tumor cells by antibody-drug conjugates (ADC) as has been clinically validated by ado-trastuzumab emtansine (Kadcyla(TM)). While selecting a suitable antibody for an ADC approach often takes specificity and efficient antibody-target complex internalization into account, the characteristics of the optimal antibody candidate remain poorly understood. We studied a large panel of human HER2 antibodies to identify the characteristics that make them most suitable for an ADC approach. As a model toxin, amenable to in vitro high-throughput screening, we employed Pseudomonas exotoxin A (ETA') fused to an anti-kappa light chain domain antibody. Cytotoxicity induced by HER2 antibodies, which were thus non-covalently linked to ETA', was assessed for high and low HER2 expressing tumor cell lines and correlated with internalization and downmodulation of HER2 antibody-target complexes. Our results demonstrate that HER2 antibodies that do not inhibit heterodimerization of HER2 with related ErbB receptors internalize more efficiently and show greater ETA'-mediated cytotoxicity than antibodies that do inhibit such heterodimerization. Moreover, stimulation with ErbB ligand significantly enhanced ADC-mediated tumor kill by antibodies that do not inhibit HER2 heterodimerization. This suggests that the formation of HER2/ErbB-heterodimers enhances ADC internalization and subsequent killing of tumor cells. Our study indicates that selecting HER2 ADCs that allow piggybacking of HER2 onto other ErbB receptors provides an attractive strategy for increasing ADC delivery and tumor cell killing capacity to both high and low HER2 expressing tumor cells.

  5. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  6. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of bench-marking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  7. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  8. The medical dictionary for regulatory activities (MedDRA).

    Science.gov (United States)

    Brown, E G; Wood, L; Wood, S

    1999-02-01

    The International Conference on Harmonisation has agreed upon the structure and content of the Medical Dictionary for Regulatory Activities (MedDRA) version 2.0 which should become available in the early part of 1999. This medical terminology is intended for use in the pre- and postmarketing phases of the medicines regulatory process, covering diagnoses, symptoms and signs, adverse drug reactions and therapeutic indications, the names and qualitative results of investigations, surgical and medical procedures, and medical/social history. It can be used for recording adverse events and medical history in clinical trials, in the analysis and tabulations of data from these trials and in the expedited submission of safety data to government regulatory authorities, as well as in constructing standard product information and documentation for applications for marketing authorisation. After licensing of a medicine, it may be used in pharmacovigilance and is expected to be the preferred terminology for international electronic regulatory communication. MedDRA is a hierarchical terminology with 5 levels and is multiaxial: terms may exist in more than 1 vertical axis, providing specificity of terms for data entry and flexibility in data retrieval. Terms in MedDRA were derived from several sources including the WHO's adverse reaction terminology (WHO-ART), Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART), International Classification of Diseases (ICD) 9 and ICD9-CM. It will be maintained, further developed and distributed by a Maintenance Support Services Organisation (MSSO). It is anticipated that using MedDRA will improve the quality of data captured on databases, support effective analysis by providing clinically relevant groupings of terms and facilitate electronic communication of data, although as a new tool, users will need to invest time in gaining expertise in its use.

  9. Strengthening Regulatory Competence in Pakistan

    International Nuclear Information System (INIS)

    Sadiq, M.

    2016-01-01

    Capacity building of Pakistan Nuclear Regulatory Authority is considered an essential element in pursuit of its vision to become a world class regulatory body. Since its inception in 2001, PNRA has continuously endeavoured to invest in its people, develop training infrastructure and impart sound knowledge and professional skills with the aim to improve its regulatory effectiveness. The use of nuclear and radioactive material in Pakistan has increased manifold in recent years, thus induction of more manpower was needed for regulatory oversight. PNRA adopted two pronged approach for meeting the manpower demand (a) employment of university graduates through fast track recruitment drive and (b) induction of graduates by offering fellowships for Master degree programs. Although, the newly employed staff was selected on the basis of their excellent academic qualifications in basic and applied sciences, but they required rigorous knowledge and skills in regulatory perspectives. In order to implement a structured training program, PNRA conducted Training Needs Assessment (TNA) and identified competency gaps of the regulatory staff in legal, technical, regulatory practice and behavioural domains. PNRA took several initiatives for capacity building which included establishment of a training centre for sustainability of trainings, initiation of a fellowship scheme for Master program, attachment of staff at local institutes for on-the-job training and placement at foreign regulatory bodies and organizations for technical development with the assistance of IAEA. The above strategies have been very beneficial in competence building of the PNRA staff to perform all regulatory activities indigenously for nuclear power plants, research reactors and radiation facilities. Provision of vibrant technical support to IAEA and Member States in various programs by PNRA is a landmark of these competence development efforts. This paper summarizes PNRA initiatives and the International Atomic

  10. The regulatory framework in the UK

    International Nuclear Information System (INIS)

    O'Sullivan, R.

    1984-01-01

    The subject is covered in sections, headed: basic regulatory requirements covering the transport of radioactive material in the UK; responsibility for safety (competent authority; provision of regulations; implementation of regulations (international and national); design of transport flask; safety case; testing; assessment; approval certificate; compliance assurance; administration); advice and information on the regulatory safety standards. (U.K.)

  11. The principle of prohibition and the closing of international law as a regulatory system; Hans Kelsen and the history of a boat

    Directory of Open Access Journals (Sweden)

    Natalia M. Luterstein

    2017-06-01

    Full Text Available This papers examines the impact of the dictum of the Permanent Court of International Justice in the “S.S. Lotus” case when it stated that “restrictions upon the independence of States cannot be presumed” and that “the rules of law binding upon States therefore emanate from their own free will as expressed in conventions or by usages generally accepted as expressing principles of law” on the interpretation and the functioning of the international legal order in light of the theory of Hans Kelsen and the critics advanced by Carlos Alchourrón and Eugenio Bulygin regarding the principle of prohibition and completeness of the normative legal systems.

  12. Direct association of thioredoxin-1 (TRX) with macrophage migration inhibitory factor (MIF): regulatory role of TRX on MIF internalization and signaling.

    Science.gov (United States)

    Son, Aoi; Kato, Noriko; Horibe, Tomohisa; Matsuo, Yoshiyuki; Mochizuki, Michika; Mitsui, Akira; Kawakami, Koji; Nakamura, Hajime; Yodoi, Junji

    2009-10-01

    Thioredoxin-1 (TRX) is a small (14 kDa) multifunctional protein with the redox-active site Cys-Gly-Pro-Cys. Macrophage migration inhibitory factor (MIF) is a 12 kDa cytokine belonging to the TRX family. Historically, when we purified TRX from the supernatant of ATL-2 cells, a 12 kDa protein was identified along with TRX, which was later proved to be MIF. Here, we show that TRX and MIF form a complex in the cell and the culture supernatant of ATL-2 cells. Using a BIAcore assay, we confirmed that TRX has a specific affinity with MIF. We also found that extracellular MIF was more effectively internalized into the ATL-2 cells expressing TRX on the cell surface, than the Jurkat T cells which do not express surface TRX. Moreover, anti-TRX antibody blocked the MIF internalization, suggesting that the cell surface TRX is involved in MIF internalization into the cells. Furthermore, anti-TRX antibody inhibited MIF-mediated enhancement of TNF-alpha production from macrophage RAW264.7 cells. These results suggest that the cell surface TRX serves as one of the MIF binding molecules or MIF receptor component and inhibits MIF-mediated inflammatory signals.

  13. Strategic information is everyone's business: perspectives from an international stakeholder meeting to enhance strategic information data along the HIV Cascade for people who inject drugs.

    Science.gov (United States)

    Pierce, Richard D; Hegle, Jennifer; Sabin, Keith; Agustian, Edo; Johnston, Lisa G; Mills, Stephen; Todd, Catherine S

    2015-10-16

    People who inject drugs (PWID) are at increased HIV transmission risk because of unsafe injecting practices and a host of other individual, network, and structural factors. Thus, PWID have a great need for services within the Cascade of HIV prevention, diagnosis, care, and treatment (HIV Cascade). Yet the systems that monitor their progress through the Cascade are often lacking. Subsequently, fewer reliable data are available to guide programs targeting this key population (KP). Programmatic data, which are helpful in tracking PWID through the Cascade, also are limited because not all countries have harm reduction programming from which to estimate Cascade indicators. Also, due to stigma and the illegal nature of drug use, PWID may not disclose their drug use behavior or HIV status when accessing services. Consequently, PWID appear to have low HIV testing rates and, for those living with HIV, lower access to health services and lower viral suppression rates than do other KP groups. This commentary, based on outcomes from an international stakeholder meeting, identifies data gaps and proposes solutions to strengthen strategic information (SI), the systematic collection, analysis, and dissemination of information, to optimize HIV prevention, care, and treatment programming for PWID.

  14. Regulatory mark; Marco regulatorio

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter is based on a work performed in distinct phases. The first phase consisted in of the analysis regulatory legislation existent in Brazil for the sugar-alcohol sector since the beginning of the X X century. This analysis allowed the identification of non existent points and legal devices related to the studied aspects, and that were considered as problematic for the sector expansion. In the second phase, related treaties and international agreements was studied and possible obstacles for the brazilian bio ethanol exportation for the international market. Initiatives were examined at European Union, United States of America, Caribbean and countries of the sub-Saharan Africa. In this phase, policies were identified related to the incentives and adoption of use of bio fuels added to the gasoline in countries or group of countries considered as key for the consolidation of bio ethanol as a world commodity.

  15. Regulatory pathways for vaccines for developing countries.

    Science.gov (United States)

    Milstien, Julie; Belgharbi, Lahouari

    2004-01-01

    Vaccines that are designed for use only in developing countries face regulatory hurdles that may restrict their use. There are two primary reasons for this: most regulatory authorities are set up to address regulation of products for use only within their jurisdictions and regulatory authorities in developing countries traditionally have been considered weak. Some options for regulatory pathways for such products have been identified: licensing in the country of manufacture, file review by the European Medicines Evaluation Agency on behalf of WHO, export to a country with a competent national regulatory authority (NRA) that could handle all regulatory functions for the developing country market, shared manufacturing and licensing in a developing country with competent manufacturing and regulatory capacity, and use of a contracted independent entity for global regulatory approval. These options have been evaluated on the basis of five criteria: assurance of all regulatory functions for the life of the product, appropriateness of epidemiological assessment, applicability to products no longer used in the domestic market of the manufacturing country, reduction of regulatory risk for the manufacturer, and existing rules and regulations for implementation. No one option satisfies all criteria. For all options, national infrastructures (including the underlying regulatory legislative framework, particularly to formulate and implement local evidence-based vaccine policy) must be developed. WHO has led work to develop this capacity with some success. The paper outlines additional areas of action required by the international community to assure development and use of vaccines needed for the developing world. PMID:15042235

  16. Advancing drug availability-experiences from Africa.

    Science.gov (United States)

    Powell, Richard A; Kaye, Richard Mugula; Ddungu, Henry; Mwangi-Powell, Faith

    2010-07-01

    International health and drug regulatory authorities acknowledge that analgesics (especially opioids) are insufficiently available for pain management in many countries. In Africa, reported morphine consumption is far below the global mean, with multiple factors hampering opioid supply. Since 2006, the African Palliative Care Association has hosted three regional drug availability workshops across the continent to address this issue. Using an interactive format, the workshops have identified country-specific barriers to opioid and other essential medication accessibility before supporting participants to develop action plans to address recognized impediments. Despite multiple challenges, a number of successes have arisen from the implementation of the plans. However, key issues remain, including the introduction of supportive policy environments, effective educational initiatives, and measures to address supply-chain obstacles impeding drug availability. Copyright 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  17. [Regulatory Program for Medical Devices in Cuba: experiences and current challenges].

    Science.gov (United States)

    Pereira, Dulce María Martínez; Rodríguez, Yadira Álvarez; Valdés, Yamila Cedeño; Ribas, Silvia Delgado

    2016-05-01

    Regulatory control of medical devices in Cuba is conducted through a system based on the Regulatory Program for Medical Devices as a way to ensure the safety, efficacy, and effectiveness of these technologies, which are in use by the National Health System. This program was launched in 1992, when the Regulations for State Evaluation and Registration of Medical Devices were approved. Its successive stages and the merging of regulatory activities for drugs and medical equipment have meant progress toward stronger, more transparent strategies and greater control of industry and the National Health System. Throughout its course the Cuban program has met with challenges and difficulties that it has addressed by drawing on its own experiences. During the new period, the greatest challenges revolve around ensuring that regulatory systems incorporate scientific evaluation, risk levels, maximum rigor through the use of technical standards, and the implementation of international recommendations, together with the application of the ISO 13485 certification scheme, enhanced market monitoring, and classification of medical devices in accordance with their relevance to the country's national health policies. From the regional standpoint, the greatest challenge lies in working toward regulatory convergence. The Collaborating Centre for the Regulation of Health Technologies will support the proposed regulatory strategy and established regional priorities, in particular in connection with the implementation of actions involving medical devices.

  18. Clinical evaluation of internal iliac artery anticancer drug infusion for the treatment of androgen-independent prostate cancer

    International Nuclear Information System (INIS)

    Cao Ye; Wang Jin; Nie Yong; Chen Hua; Huang Xinjie

    2008-01-01

    Objective: To evaluate the clinical efficacy of bilateral internal iliac artery chemotherapy infusion for the treatment of androgen-independent prostate cancer (ALPC). Methods: Thirty eight eases of confirmed AIPC were randomly divided into treatment group and control group. The patients in treatment group (23 cases) were treated with androgen deprivation therapy and regular internal iliac artery chemotherapy, while patients in control group (15 cases) were only received androgen deprivation therapy. The therapeutic efficacies of the two groups were compared and analyzed after completion of the treatment. Results: The clinical symptoms and maximum urine flow rates of' treatment group were improved rapidly 6 months later. After 2 years follow-up, the total efficacies of treatment group and control group were 65.2% and 26.7% respectively, showing a significant statistical difference (P<0.05). Conclusions: The treatment of AlPC with bilateral internal iliac artery chemotherapy is effective, providing melioration the quality of life and alleviation of the symptoms. (authors)

  19. The burgeoning recognition and accommodation of the social supply of drugs in international criminal justice systems: An eleven-nation comparative overview.

    Science.gov (United States)

    Coomber, Ross; Moyle, Leah; Belackova, Vendula; Decorte, Tom; Hakkarainen, Pekka; Hathaway, Andrew; Laidler, Karen Joe; Lenton, Simon; Murphy, Sheigla; Scott, John; Stefunkova, Michaela; van de Ven, Katinka; Vlaemynck, Marieke; Werse, Bernd

    2018-06-08

    It is now commonly accepted that there exists a form of drug supply, that involves the non-commercial supply of drugs to friends and acquaintances for little or no profit, which is qualitatively different from profit motivated 'drug dealing proper'. 'Social supply', as it has become known, has a strong conceptual footprint in the United Kingdom, shaped by empirical research, policy discussion and its accommodation in legal frameworks. Though scholarship has emerged in a number of contexts outside the UK, the extent to which social supply has developed as an internationally recognised concept in criminal justice contexts is still unclear. Drawing on an established international social supply research network across eleven nations, this paper provides the first assessment of social supply as an internationally relevant concept. Data derives from individual and team research stemming from Australia, Belgium, Canada, Czech Republic, Finland, Germany, Hong Kong, the Netherlands, England and Wales, and the United States, supported by expert reflection on research evidence and analysis of sentencing and media reporting in each context. In situ social supply experts addressed a common set of questions regarding the nature of social supply for their particular context including: an overview of social supply research activity, reflection on the extent that differentiation is accommodated in drug supply sentencing frameworks; evaluating the extent to which social supply is recognised in legal discourse and in sentencing practices and more broadly by e.g. criminal justice professionals in the public sphere. A thematic analysis of these scripts was undertaken and emergent themes were developed. Whilst having an absence of local research, New Zealand is also included in the analysis as there exists a genuine discursive presence of social supply in the drug control and sentencing policy contexts in that country. Findings suggest that while social supply has been found to exist as

  20. Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.

    Science.gov (United States)

    Church, Rachel J; Kullak-Ublick, Gerd A; Aubrecht, Jiri; Bonkovsky, Herbert L; Chalasani, Naga; Fontana, Robert J; Goepfert, Jens C; Hackman, Frances; King, Nicholas M P; Kirby, Simon; Kirby, Patrick; Marcinak, John; Ormarsdottir, Sif; Schomaker, Shelli J; Schuppe-Koistinen, Ina; Wolenski, Francis; Arber, Nadir; Merz, Michael; Sauer, John-Michael; Andrade, Raul J; van Bömmel, Florian; Poynard, Thierry; Watkins, Paul B

    2018-01-22

    Current blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of fourteen promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n=192 and =81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n=55 and =92) and DILI patients (n=98, =28, and =143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total keratin 18 (K18), caspase cleaved K18 (ccK18), glutathione S-transferase alpha (GSTα), alpha fetoprotein (AFP), arginase-1 (ARG1), osteopontin (OPN), sorbitol dehydrogenase (SDH), fatty acid binding protein (FABP1), cadherin-5 (CDH5), macrophage colony stimulating factor receptor (MCSFR), paraoxonase 1 (PON1, normalized to prothrombin protein), and leucocyte cell-derived chemotaxin-2 (LECT2). Most candidate biomarkers were significantly altered in DILI cases compared to healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase (ALT) than miR-122 and there was a surprisingly wide inter- and intra-individual variability of miR-122 levels among the healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver-related death or transplant within 6 months of DILI-onset. Prediction of prognosis among DILI patients using Model for End-stage Liver Disease (MELD) was improved by incorporation of K18 and MCSFR levels. GLDH appears to be more useful than miR-122 in identifying DILI patients. K18, OPN and MCSFR are promising candidates for prediction of prognosis during an acute DILI event. Serial assessment of these biomarkers in large prospective studies will help further delineate their role in DILI diagnosis and management. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  1. Annual Report 2010. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2010-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across six chapters and seven annexes the activities developed by the organism during 2010. The main topic are: institutional issues; regulatory guides and standards; argentinean nuclear regulatory system; quality assurance of the ARN; the institutional communications; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the safeguards and the physical protection; the environmental control; the institutional relations; the training and the public information. Also, this publication have annexes with the following content: the regulatory framework; regulatory documents; inspections to medical, industrial and training installations; measurement and evaluation of the drinking water of Ezeiza; international expert's report on the application of the international standards of radiological protection of the public in the zone of the Ezeiza Atomic Center; ethical code

  2. Annual Report 2011. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2011-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across six chapters and seven annexes the activities developed by the organism during 2011. The main topic are: institutional issues; regulatory guides and standards; argentinean nuclear regulatory system; quality assurance of the ARN; the institutional communications; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the safeguards and the physical protection; the environmental control; the institutional relations; the training and the public information. Also, this publication have annexes with the following content: the regulatory framework; regulatory documents; inspections to medical, industrial and training installations; measurement and evaluation of the drinking water of Ezeiza; international expert's report on the application of the international standards of radiological protection of the public in the zone of the Ezeiza Atomic Center; ethical code

  3. Safety culture as a matter of regulatory control and regulatory effectiveness

    International Nuclear Information System (INIS)

    Camargo, C.T.M.; Furieri, E.B.; Arrieta, L.A.I.; Almeida, C.U.C.

    2002-01-01

    More than 15 years have passed since the term 'safety culture' was introduced by the International Nuclear Safety Advisory Group (INSAG), and although the concept now is widely accepted, practical applications and characteristics have been disseminated mainly for nuclear power plant operating organizations. There is still a lack of international guidance on the use of safety culture as a regulatory matter and on the application of the concept within regulatory organizations. This work explores the meaning of safety culture in two different fields: as an element of safety management systems it shall be a matter of regulatory control; as a complementary tool for quality management it should be used to enhance regulatory effectiveness. Brazilian recent experience on regulating nuclear power reactors provide some examples on how the concept of safety culture may influence regulatory strategies and regulatory management. (author)

  4. Reduced antituberculosis drug concentrations in HIV-infected patients who are men or have low weight: implications for international dosing guidelines.

    Science.gov (United States)

    McIlleron, Helen; Rustomjee, Roxana; Vahedi, Mahnaz; Mthiyane, Thuli; Denti, Paolo; Connolly, Catherine; Rida, Wasima; Pym, Alexander; Smith, Peter J; Onyebujoh, Philip C

    2012-06-01

    Reduced antituberculosis drug concentrations may contribute to unfavorable treatment outcomes among HIV-infected patients with more advanced immune suppression, and few studies have evaluated pharmacokinetics of the first-line antituberculosis drugs in such patients given fixed-dose combination tablets according to international guidelines using weight bands. In this study, pharmacokinetics were evaluated in 60 patients on 4 occasions during the first month of antituberculosis therapy. Multilevel linear mixed-effects regression analysis was used to examine the effects of age, sex, weight, drug dose/kilogram, CD4(+) lymphocyte count, treatment schedule (5 versus 7 days/week), and concurrent antiretrovirals (efavirenz plus lamivudine plus zidovudine) on the area under the concentration-time curve from 0 to 12 h (AUC(0-12)) of the respective antituberculosis drugs and to compare AUC(0-12)s at day 8, day 15, and day 29 with the day 1 AUC(0-12). Median (range) age, weight, and CD4(+) lymphocyte count were 32 (18 to 47) years, 55.2 (34.4 to 98.7) kg, and 252 (12 to 500)/μl. For every 10-kg increase in body weight, the predicted day 29 AUC(0-12) increased by 14.1% (95% confidence interval [CI], 7.5, 20.8), 14.1% (95% CI, -0.7, 31.1), 6.1% (95% CI, 2.7, 9.6) and 6.0% (95% CI, 0.8, 11.3) for rifampin, isoniazid, pyrazinamide, and ethambutol, respectively. Males had day 29 AUC(0-12)s 19.3% (95% CI, 3.6, 35.1) and 14.0% (95% CI, 5.6, 22.4) lower than females for rifampin and pyrazinamide, respectively. Level of immune suppression and concomitant antiretrovirals had little effect on the concentrations of the antituberculosis agents. As they had reduced drug concentrations, it is important to review treatment responses in patients in the lower weight bands and males to inform future treatment guidelines, and revision of doses in these patients should be considered.

  5. Regulatory framework for the management of radioactive wastes in Argentina

    International Nuclear Information System (INIS)

    D'Amato, E.; Siraky, G.; Petraitis, E.; Novo, R.

    2000-01-01

    The legal and regulatory framework within which the radioactive waste management is carried out in Argentina are exposed. The activities of the Nuclear Regulatory Authority (ARN) in relation to facility inspections, safety assessments and collaboration with international agencies in the matter are also presented. Further, the regulatory criteria applied to waste management are reported. (author)

  6. Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric acute lymphocytic leukemia (ALL): review from an international consensus conference.

    Science.gov (United States)

    Horton, Terzah M; Sposto, Richard; Brown, Patrick; Reynolds, C Patrick; Hunger, Stephen P; Winick, Naomi J; Raetz, Elizabeth A; Carroll, William L; Arceci, Robert J; Borowitz, Michael J; Gaynon, Paul S; Gore, Lia; Jeha, Sima; Maurer, Barry J; Siegel, Stuart E; Biondi, Andrea; Kearns, Pamela R; Narendran, Aru; Silverman, Lewis B; Smith, Malcolm A; Zwaan, C Michel; Whitlock, James A

    2010-07-01

    One of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute lymphocytic leukemia (ALL) experts addressed this issue (www.ALLNA.org). Two major questions surrounding DLT assessment were explored: (1) how toxicities can be best defined, assessed, and attributed; and (2) how effective dosing of new agents incorporated into multi-agent ALL clinical trials can be safely established in the face of disease- and therapy-related systemic toxicities. The consensus DLT definition incorporates tolerance of resolving Grade 3 and some resolving Grade 4 toxicities with stringent safety monitoring. This functional DLT definition is being tested in two Children's Oncology Group (COG) ALL clinical trials. Copyright 2010 Wiley-Liss, Inc.

  7. Discussion on building safety culture inside a nuclear safety regulatory body

    International Nuclear Information System (INIS)

    Fan Yumao

    2013-01-01

    A strong internal safety culture plays a key role in improving the performance of a nuclear regulatory body. This paper discusses the definition of internal safety culture of nuclear regulatory bodies, and explains the functions that the safety culture to facilitate the nuclear safety regulation and finally puts forward some thoughts about building internal safety culture inside regulatory bodies. (author)

  8. Application of Resource Portfolio Concept in Nuclear Regulatory Infrastructure Support

    International Nuclear Information System (INIS)

    Lee, Y. E.; Ha, J. T.; Chang, H. S.; Kam, S. C.; Ryu, Y. H.

    2010-01-01

    As the new entrants in the global nuclear construction market are increasing and the establishment of an effective and sustainable regulatory infrastructure becomes more important, they have requested international assistance from the international nuclear communities with mature nuclear regulatory programmes. It needs to optimize the use of limited resources from regulatory organization providing support to regulatory infrastructure of new comers. This paper suggests the resource portfolio concept like a GE/Mckinsey Matrix used in business management and tries to apply it to the current needs considered in the regulatory support program in Korea as the case study

  9. Illegal "no prescription" internet access to narrow therapeutic index drugs.

    Science.gov (United States)

    Liang, Bryan A; Mackey, Tim K; Lovett, Kimberly M

    2013-05-01

    Narrow therapeutic index (NTI) drugs, because of proximity of therapeutic amounts to toxic amounts, require close professional oversight, particularly when switching formulations. However, safe use may be compromised by unsupervised switching through access to online "no prescription" Web sites. We assessed no prescription online availability of NTI drugs, using an academically published list (core NTI drugs). Using the Google search term "buy DRUG no prescription," we reviewed the first 5 search result pages for marketing of no prescription NTI drugs. We further assessed if National Association of Boards of Pharmacy (NABP) Not Recommended vendors were marketing NTI drugs. Searches were conducted from November 3, 2012 to January 3, 2013. For core NTI drugs, we found 13 of 14 NTI drugs (92%) marketed as available without prescription, all from NABP Not Recommended vendors. On the basis of these initial findings, we expanded our core list to 12 additional NTI drugs; 11 of 12 of these drugs (92%) were available from no prescription Web sites. Overall, 24 of 26 NTI drugs (92%) were illegally marketed as available online without the need for a prescription. Suspect online NTI drug access from no prescription vendors represents a significant patient safety risk because of potential patient drug switching and risk of counterfeit versions. Further, state health care exchanges with coverage limitations may drive patients to seek formulations online. Food and Drug Administration harmonization with tighter international NTI drug standards should be considered, and aggressive action against suspect online marketers should be a regulatory and public health priority. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

  10. Radioactive waste below regulatory concern

    International Nuclear Information System (INIS)

    Neuder, S.M.

    1987-01-01

    The U.S. Nuclear Regulatory Commission (NRC) published two notices in the Federal Register concerning radioactive waste below regulatory concern. The first, a Commission Policy Statement and Implementation Plan published August 29, 1986, concerns petition to exempt specific radioactive waste streams from the regulations. The second, an Advanced Notice of Proposed Rulemaking published Decemger 2, 1986, addresses the concept of generic rulemaking by the NRC on radioactive wastes that are below regulatory concern. Radioactive waste determined to be below regulatory concern would not be subject to regulatory control and would not need to go to a licensed low-level radioactive waste disposal site. The Policy Statement and Implementation Plan describe (1) the information a petitioner should file in support of a petition to exempt a specific waste stream, (2) the decision criteria the Commission intends to use for judging the petition, and (3) the internal administrative procedures to use be followed in order to permit the Commission to act upon the petition in an expedited manner

  11. The Regulatory Independence of FANR

    International Nuclear Information System (INIS)

    ALNuaimi, Fatema; Choi, Kwang Shik

    2012-01-01

    Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

  12. The Regulatory Independence of FANR

    Energy Technology Data Exchange (ETDEWEB)

    ALNuaimi, Fatema; Choi, Kwang Shik [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2012-05-15

    Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

  13. Nuclear Regulatory Commission Issuances

    International Nuclear Information System (INIS)

    1992-01-01

    This is the thirty-sixth volume of issuances (1-396) of the Nuclear Regulatory Commission and its Atomic Safety and Licensing Boards, Administrative Law Judges, and Office Directors. It covers the period from July 1, 1992-December 31, 1992. Atomic Safety and Licensing Boards are authorized by Section 191 of the Atomic Energy Act of 1954. These Boards, comprised of three members conduct adjudicatory hearings on applications to construct and operate nuclear power plants and related facilities and issue initial decisions which, subject to internal review and appellate procedures, become the final Commission action with respect to those applications. Boards are drawn from the Atomic Safety and Licensing Board Panel, comprised of lawyers, nuclear physicists and engineers, environmentalists, chemists, and economists. The Atomic Energy Commission first established Licensing Boards in 1962 and the Panel in 1967

  14. As to achieve regulatory action, regulatory approaches

    International Nuclear Information System (INIS)

    Cid, R.; Encinas, D.

    2014-01-01

    The achievement of the effectiveness in the performance of a nuclear regulatory body has been a permanent challenge in the recent history of nuclear regulation. In the post-Fukushima era this challenge is even more important. This article addresses the subject from two complementary points of view: the characteristics of an effective regulatory body and the regulatory approaches. This work is based on the most recent studies carried out by the Committee on Nuclear Regulatory Activities, CNRA (OECD/NEA), as well as on the experience of the Consejo de Seguridad Nuclear, CSN, the Spanish regulatory body. Rafael Cid is the representative of CSN in these project: Diego Encinas has participated in the study on regulatory approaches. (Author)

  15. Regulatory inspection of nuclear facilities and enforcement by the regulatory body. Safety guide

    International Nuclear Information System (INIS)

    2002-01-01

    The purpose of this Safety Guide is to provide recommendations for regulatory bodies on the inspection of nuclear facilities, regulatory enforcement and related matters. The objective is to provide the regulatory body with a high level of confidence that operators have the processes in place to ensure compliance and that they do comply with legal requirements, including meeting the safety objectives and requirements of the regulatory body. However, in the event of non-compliance, the regulatory body should take appropriate enforcement action. This Safety Guide covers regulatory inspection and enforcement in relation to nuclear facilities such as: enrichment and fuel manufacturing plants; nuclear power plants; other reactors such as research reactors and critical assemblies; spent fuel reprocessing plants; and facilities for radioactive waste management, such as treatment, storage and disposal facilities. This Safety Guide also covers issues relating to the decommissioning of nuclear facilities, the closure of waste disposal facilities and site rehabilitation. Section 2 sets out the objectives of regulatory inspection and enforcement. Section 3 covers the management of regulatory inspections. Section 4 covers the performance of regulatory inspections, including internal guidance, planning and preparation, methods of inspection and reports of inspections. Section 5 deals with regulatory enforcement actions. Section 6 covers the assessment of regulatory inspections and enforcement activities. The Appendix provides further details on inspection areas for nuclear facilities

  16. Impact assessment of the European Clinical Trials Directive: a longitudinal, prospective, observational study analyzing patterns and trends in clinical drug trial applications submitted since 2001 to regulatory agencies in six EU countries

    Directory of Open Access Journals (Sweden)

    Hartmann Markus

    2012-04-01

    Full Text Available Abstract Background Shifts in clinical trial application rates over time indicate if the attractiveness of a country or region for the conduct of clinical trials is growing or decreasing. The purpose of this observational study was to track changes in drug trial application patterns across several EU countries in order to analyze the medium-term impact of the EU Clinical Trials Directive 2001/20/EC on the conduct of drug trials. Methods Rates of Clinical Trial Applications (CTA for studies with medicinal products in those six countries in the EU, which authorize on average more than 500 trials per year, were analyzed. Publicly available figures on the number of annually submitted CTA, the distribution of trials per phase and the type of sponsorship were tracked; missing data were provided by national drug agencies. Results Since 2001, the number of CTA in Italy and Spain increased significantly (5.0 and 2.5% average annual growth. For Italy, the gain was driven by a strong increase of applications from academic trial sponsors; Spain's growth was due to a rise in trials run by commercial sponsors. The Netherlands, Germany, France and the UK saw a decline (1.9, 2.3, 3.0 and 5.3% average annual diminution; significant (P Conclusions The EU Clinical Trials Directive 2001/20/EC did not achieve the harmonization of clinical trial requirements across Europe. Rather, it resulted in the leveling of clinical trial activities caused by a continuing decrease in CTA rates in the Netherlands, Germany, France and the UK. Southern European countries, Italy and Spain, benefited to some extent from policy changes introduced by the Directive. In Italy's case, national funding measures helped to considerably promote the conduct of non-commercial trials. On the other hand, the EU Directive-driven transition from liberal policy environments, based on non-explicit trial approval through notifications, towards red-taped processes of trial authorization, contributed to

  17. Regulatory aspects of NPP safety

    International Nuclear Information System (INIS)

    Kastchiev, G.

    1999-01-01

    Extensive review of the NPP Safety is presented including tasks of Ministry of Health, Ministry of Internal Affairs, Ministry of Environment and Waters, Ministry of Defense in the field of national system for monitoring the nuclear power. In the frame of national nuclear safety legislation Bulgaria is in the process of approximation of the national legislation to that of EC. Detailed analysis of the status of regulatory body, its functions, organisation structure, responsibilities and future tasks is included. Basis for establishing the system of regulatory inspections and safety enforcement as well as intensification of inspections is described. Assessment of safety modifications is concerned with complex program for reconstruction of Units 1-4 of Kozloduy NPP, as well as for modernisation of Units 5 and 6. Qualification and licensing of the NPP personnel, Year 2000 problem, priorities and the need of international assistance are mentioned

  18. Pharma Opportunities and Risks Multiply as Regulatory Reform Remakes APAC: Expanded Accelerated Pathways Challenge Developer Value Story, Evidence Collection, and Market Access Strategies.

    Science.gov (United States)

    Grignolo, Alberto; Mingping, Zhang

    2018-01-01

    Sweeping reforms in the largest markets of the Asia-Pacific region are transforming the regulatory and commercial landscape for foreign pharmaceutical companies. Japan, South Korea, and China are leading the charge, establishing mechanisms and infrastructure that both reflect and help drive international regulatory convergence and accelerate delivery of needed, innovative products to patients. In this rapidly evolving regulatory and commercial environment, drug developers can benefit from reforms and proliferating accelerated pathway (AP) frameworks, but only with regulatory and evidence-generation strategies tailored to the region. Otherwise, they will confront significant pricing and reimbursement headwinds. Although APAC economies are at different stages of development, they share a common imperative: to balance pharmaceutical innovation with affordability. Despite the complexity of meeting these sometimes conflicting demands, companies that focus on demonstrating and delivering value for money, and that price new treatments reasonably and sustainably, can succeed both for their shareholders and the region's patient population.

  19. Correlation between Drug Market Withdrawals and Socioeconomic, Health, and Welfare Indicators Worldwide.

    Science.gov (United States)

    Lee, Kye Hwa; Kim, Grace Juyun; Kim, Ju Han

    2015-11-01

    The relationship between the number of withdrawn/restricted drugs and socioeconomic, health, and welfare indicators were investigated in a comprehensive review of drug regulation information in the United Nations (UN) countries. A total of of 362 drugs were withdrawn and 248 were restricted during 1950-2010, corresponding to rates of 12.02 ± 13.07 and 5.77 ± 8.69 (mean ± SD), respectively, among 94 UN countries. A socioeconomic, health, and welfare analysis was performed for 33 OECD countries for which data were available regarding withdrawn/restricted drugs. The gross domestic product (GDP) per capita, GDP per hour worked, health expenditure per GDP, and elderly population rate were positively correlated with the numbers of withdrawn and restricted drugs (P < 0.05), while the out-of-pocket health expenditure payment rate was negatively correlated. The number of restricted drugs was also correlated with the rate of drug-related deaths (P < 0.05). The World Bank data cross-validated the findings of 33 OECD countries. The lists of withdrawn/restricted drugs showed markedly poor international agreement between them (Fleiss's kappa = -0.114). Twenty-seven drugs that had been withdrawn internationally by manufacturers are still available in some countries. The wide variation in the numbers of drug withdrawals and restrictions among countries indicates the need to improve drug surveillance systems and regulatory communication networks.

  20. Regulatory and technical reports (abstract index journal)

    International Nuclear Information System (INIS)

    1994-03-01

    This compilation consists of bibliographic data and abstracts for the formal regulatory and technical reports issued by the US Nuclear Regulatory Commission staff and its contractors. There are four types of reports included: staff reports, conference reports, contractor reports, and international agreement reports. In addition to the main citations with abstracts, the following are also included: Secondary report number index; Personal author index; Subject index; NRC originating organization indices for staff reports and international agreement reports; NRC contract sponsor index; Contractor index; International organization index; and Licensed facility index

  1. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2015-01-01

    This section treats of the following National legislative and regulatory activities: 1 - Canada: Liability and compensation; 2 - France: Liability and compensation; Nuclear safety and radiological protection; 3 - Greece: Organisation and structure; 4 - Hungary: General legislation; 5 - India: Liability and compensation; 6 - Japan: Liability and compensation; 7 - Korea: Liability and compensation; 8 - Lithuania: General legislation; Transport of radioactive material; 9 - Slovak Republic: International co-operation; Liability and compensation; 10 - Slovenia: General legislation; 11 - Switzerland: Liability and compensation; 12 - United States: Radioactive waste management

  2. Energy drink use frequency among an international sample of people who use drugs: Associations with other substance use and well-being

    OpenAIRE

    Peacock, Amy; Bruno, Raimondo; Ferris, Jason; Winstock, Adam

    2017-01-01

    Objective The study aims were to identify: i.) energy drink (ED), caffeine tablet, and caffeine intranasal spray use amongst a sample who report drug use, and ii.) the association between ED use frequency and demographic profile, drug use, hazardous drinking, and wellbeing. Method Participants (n = 74,864) who reported drug use completed the online 2014 Global Drug Survey. They provided data on demographics, ED use, and alcohol and drug use, completed the Alcohol Use Disorders Identification ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  4. Annual Report 2013. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2010-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across seven parts and eight annexes the activities developed by the organism during 2013. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the environmental monitoring; the occupational surveillance; the training and the public information; improved organizational and budgetary developments. Also, this publication has annexes with the following content: regulatory documents; inspections to medical; presentations of publications from ARN staff; measurement and evaluation of the drinking water of Ezeiza; international expert report on the implementation of international standards on radiation protection in the Ezeiza Atomic Center; Code of Ethics of the Nuclear Regulatory Authority.

  5. Regulatory authority infrastructure for Namibia

    International Nuclear Information System (INIS)

    Shangula, K.

    2001-01-01

    The Republic of Namibia is participating in the International Atomic Energy Agency's Model Project for the Improvement of National Regulatory Authority Infrastructures in Member States. The paper illustrates our experience in solving problems and difficulties confronted in establishing an effective regulatory authority operating within the existing national infrastructure that should be supported by the Government. An effective regulatory authority is seen as part of the wider administrative scope of our Government through ministerial mandates given by the State from time to time, guaranteeing its independence when implementing legal provisions under statutes. Sections of the report illustrate our experience in the following areas: 1. National radiation protection policy 2. Structure of our national regulatory authority 3. Laws and regulations 4. Provisions for notification, authorization and registration 5. In-depth security measures for radiation sources and radioactive material 6. Systems for the inspection of radiation sources, radioactive materials, enforcement of legal provisions 7. Extent of the applications of radiation sources and radioactive materials in the country. The paper provides information regarding existing Government policy on radiation protection; structure and legal aspects of the national regulatory, including statutes and regulations; the extent of application and uses of radiation sources and security of radioactive materials; human resources: strengths and constraints; management practices and financing of regulatory authority; and plans for emergency recovery of orphan sources. National plans for management of disused sources, recovery of orphan sources, abnormal emergencies, communication of information to affected persons on exposure effects, and the safety training of persons using these applications are discussed. the paper provides a summary and some suggestions of the way forward for Namibia. (author)

  6. Professional and Regulatory Search

    Science.gov (United States)

    Professional and Regulatory search are designed for people who use EPA web resources to do their job. You will be searching collections where information that is not relevant to Environmental and Regulatory professionals.

  7. ENSI’s regulatory framework strategy

    International Nuclear Information System (INIS)

    2015-03-01

    This short brochure issued by the Swiss Federal Nuclear Safety Inspectorate ENSI defines the organisation’s regulatory framework strategy. Six guiding principles are declared and discussed: Comprehensive harmonisation with relevant international requirements, basing the regulatory framework on existing, tried-and-tested regulations, issuing of its own guidelines only when it is necessary to do so, guidelines to be drawn up transparently and with the involvement of all stakeholders and basing the level of detail of its regulatory framework on hazard potential and risk

  8. Effectiveness of controlled internal drug release device treatment to alleviate reproductive seasonality in anestrus lactating or dry Barki and Rahmani ewes during non-breeding season.

    Science.gov (United States)

    El-Mokadem, M Y; Nour El-Din, Anm; Ramadan, T A; Rashad, A M; Taha, T A; Samak, M A; Salem, M H

    2018-04-01

    This study aimed to evaluate the effectiveness of hormonal treatments on ovarian activity and reproductive performance in Barki and Rahmani ewes during non-breeding season. Forty-eight multiparous ewes, 24 Barki and 24 Rahmani ewes were divided into two groups, 12 lactating and 12 dry ewes for each breed. Controlled internal drug release (CIDR) device was inserted in all ewes for 14 days in conjunction with intramuscular 500 IU equine chronic gonadotrophin (eCG) at day of CIDR removal. Data were analysed using PROC MIXED of SAS for repeated measures. Breed, physiological status and days were used as fixed effects and individual ewes as random effects. Barki ewes recorded higher (p ewes. Lactating ewes recorded higher (p ewes. Number and diameter of large follicles recorded the highest (p ewes recorded longer (p ewes. In conclusion, CIDR-eCG protocol was more potent in improving ovarian activity in Barki compared to Rahmani ewes, but this protocol seems to induce hormonal imbalance in Barki ewes that resulted in increasing conception failure compared to Rahmani ewes. © 2017 Blackwell Verlag GmbH.

  9. Effectiveness of melatonin and controlled internal drug release device treatment on reproductive performance of buffalo heifers during out-of-breeding season under tropical conditions.

    Science.gov (United States)

    Ramadan, T A; Sharma, R K; Phulia, S K; Balhara, A K; Ghuman, S S; Singh, I

    2014-12-01

    Sixteen Murrah buffalo heifers, divided into control and treatment groups of eight animals each, were used to study the effect of melatonin and controlled internal drug release (CIDR) device treatment on the resumption of ovarian activity during out-of-breeding season (summer solstice). Treated group was implanted with melatonin (18 mg of melatonin per 50 kg of body weight) for 45 days and then heifers of both groups received CIDR for 9 days. All heifers received intramuscular 500 IU eCG on the day before CIDR removal and 10 μg GnRH on the day after CIDR withdrawal. All animals were subjected to estrus detection daily. Blood sampling in conjunction with transrectal ultrasonography were performed twice weekly to determine serum concentrations of melatonin, progesterone, LH, and antioxidant enzyme activities, as well as to monitor the ovarian follicular activity. Melatonin treatment resulted in an increase (P Days 0 and 35 of melatonin treatment. However, melatonin exhibited superior ability to maintain CL at 21 days after artificial insemenation (AI) and increased the percentage of conception to threefold higher than control. In conclusion, melatonin implantation successfully improved the diameter of largest follicles and the ability to maintain CL at 21 days after AI in buffalo heifers during out-of-breeding season under tropical conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Manipulation of reproductive performance of lactating buffaloes using melatonin and controlled internal drug release device treatment during out-of-breeding season under tropical conditions.

    Science.gov (United States)

    Ramadan, T A; Sharma, R K; Phulia, S K; Balhara, A K; Ghuman, S S; Singh, I

    2016-09-01

    Twelve lactating Murrah buffalo, divided into control and treatment group of six animals each, were used to study the effect of melatonin and controlled internal drug release (CIDR) device treatment on the resumption of ovarian activity during out-of-breeding season (summer solstice). Treated group implanted with melatonin (18-mg melatonin/50-kg body weight) for 45 days and then animals of both groups received CIDR for 9 days. All animals received intramuscular 500 IU eCG, at day before CIDR removal, and 10-μg GnRH at day after CIDR withdrawal. All animals were subjected to estrus detection daily. Blood samples in conjunction with transrectal ultrasonography were performed once a week to determine serum concentrations of melatonin, progesterone, and antioxidant enzyme activities, as well as to monitor the ovarian activity. Melatonin treatment resulted in an increase (P Day 21 and Day 30 after artificial insemination and achieved higher percentage of conception rate than control. In conclusion, the CIDR treatment preceded by melatonin improved the reproductive performance in lactating buffaloes during out-of-breeding season under tropical conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. 21 CFR 14.160 - Establishment of standing technical advisory committees for human prescription drugs.

    Science.gov (United States)

    2010-04-01

    ... and advertising, and regulatory control of the human prescription drugs falling within the... continued approval for marketing; or (3) A particular drug is properly classified as a new drug, an old drug...

  12. Which Form of Medical Training is the Best in Improving Interns' knowledge Related to Advanced Cardiac Life Support Drugs Pharmacology? An Educational Analytical Intervention Study Between Electronic Learning and Lecture-Based Education.

    Science.gov (United States)

    Khoshbaten, Manouchehr; Soleimanpour, Hassan; Ala, Alireza; Shams Vahdati, Samad; Ebrahimian, Kimia; Safari, Saeid; Golzari, Samad Ej; Salek Ranjbarzadeh, Fariba; Mehdizadeh Esfanjani, Robab

    2014-02-01

    Conventional educational systems seem to be improper throughout the cardiopulmonary resuscitation (CPR) teaching process. The most common causes of failed resuscitation are unfamiliarity with cardiopulmonary resuscitation algorithms, poor performance of leader of the CPR team and lack of skilled personnel, coordination among members during resuscitation, and responsibility of staff. Electronic learning, as a new educational method is controversial issue in medical education for improving physicians' practical knowledge and it is inevitable that further research on its effectiveness should be done. The present study is a prospective, pre- and post-educational, cross-sectional research, in which 84 interns were randomly divided into two groups. pre- and post- educational interventions that took place in the Department of Emergency Medicine, interns were evaluated by 21 multiple choice questions related to American Heart Association guidelineson cardiopulmonary resuscitation drugs. Questions were assessed in terms of routes for CPR drugs administration, CPR drug dosage forms, clinical judgment and appropriate CPR drug administration, and the alternative drugs in emergency situations. Data were analyzed by generalized estimating equations regression models and P methods revealed that the mean answering score for 21 questions before education was 7.5 ± 2.6 and no significant difference was observed in groups (P = 0.55). However, after education, the average scores significantly increased to 11.0 ± 3.9 (P method was not associated with considerable increase in the knowledge of interns in this group compared with the lecture-based group (P = 0.49). No significant differences were observed between electronic learning and lecture-based education in improving interns' knowledge of CPR drugs.

  13. Accelerating drug development for neuroblastoma - New Drug Development Strategy: an Innovative Therapies for Children with Cancer, European Network for Cancer Research in Children and Adolescents and International Society of Paediatric Oncology Europe Neuroblastoma project.

    Science.gov (United States)

    Moreno, Lucas; Caron, Hubert; Geoerger, Birgit; Eggert, Angelika; Schleiermacher, Gudrun; Brock, Penelope; Valteau-Couanet, Dominique; Chesler, Louis; Schulte, Johannes H; De Preter, Katleen; Molenaar, Jan; Schramm, Alexander; Eilers, Martin; Van Maerken, Tom; Johnsen, John Inge; Garrett, Michelle; George, Sally L; Tweddle, Deborah A; Kogner, Per; Berthold, Frank; Koster, Jan; Barone, Giuseppe; Tucker, Elizabeth R; Marshall, Lynley; Herold, Ralf; Sterba, Jaroslav; Norga, Koen; Vassal, Gilles; Pearson, Andrew Dj

    2017-08-01

    Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term toxicity and to incorporate molecularly targeted therapies into treatment. Many potential drugs are becoming available, but have to be prioritised for clinical trials due to the relatively small numbers of patients. Areas covered: The current drug development model has been slow, associated with significant attrition, and few new drugs have been developed for neuroblastoma. The Neuroblastoma New Drug Development Strategy (NDDS) has: 1) established a group with expertise in drug development; 2) prioritised targets and drugs according to tumour biology (target expression, dependency, pre-clinical data; potential combinations; biomarkers), identifying as priority targets ALK, MEK, CDK4/6, MDM2, MYCN (druggable by BET bromodomain, aurora kinase, mTORC1/2) BIRC5 and checkpoint kinase 1; 3) promoted clinical trials with target-prioritised drugs. Drugs showing activity can be rapidly transitioned via parallel randomised trials into front-line studies. Expert opinion: The Neuroblastoma NDDS is based on the premise that optimal drug development is reliant on knowledge of tumour biology and prioritisation. This approach will accelerate neuroblastoma drug development and other poor prognosis childhood malignancies.

  14. A drug's life: the pathway to drug approval.

    Science.gov (United States)

    Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

    2013-10-01

    In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

  15. Drug mules” as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Patricia M., E-mail: patricia.flach@irm.uzh.ch [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Department of Neuroradiology, Inselspital Bern, University of Bern, 3010 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Department of Radiology, University Hospital USZ, University of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Ross, Steffen G. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Ampanozi, Garyfalia; Ebert, Lars [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Germerott, Tanja; Hatch, Gary M. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Thali, Michael J. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Patak, Michael A. [Department of Radiology, Inselspital Bern, University of Bern, 3010 Bern (Switzerland); Department of Radiology, University Hospital USZ, University of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland)

    2012-10-15

    Purpose: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox{sup ®}) in the detection of internal cocaine containers. Methods: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16–45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT = 35, nDR = 70, nLSDR = 30. An overall calculation of all “drug mules” and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. Results: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. Conclusions: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage.

  16. Drug mules” as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

    International Nuclear Information System (INIS)

    Flach, Patricia M.; Ross, Steffen G.; Ampanozi, Garyfalia; Ebert, Lars; Germerott, Tanja; Hatch, Gary M.; Thali, Michael J.; Patak, Michael A.

    2012-01-01

    Purpose: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox ® ) in the detection of internal cocaine containers. Methods: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16–45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT = 35, nDR = 70, nLSDR = 30. An overall calculation of all “drug mules” and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. Results: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. Conclusions: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage

  17. Future nuclear regulatory challenges

    International Nuclear Information System (INIS)

    Royen, J.

    1998-01-01

    In December 1996, the NEA Committee on Nuclear Regulatory Activities concluded that changes resulting from economic deregulation and other recent developments affecting nuclear power programmes have consequences both for licensees and regulatory authorities. A number of potential problems and issues which will present a challenge to nuclear regulatory bodies over the next ten years have been identified in a report just released. (author)

  18. 78 FR 38053 - Regulatory Systems Strengthening

    Science.gov (United States)

    2013-06-25

    ... current state of medical product regulation globally, including challenges, risks, and emerging trends... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0010... product regulation; generation and analysis of evidence of regulatory systems performance; and provision...

  19. Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.

    Science.gov (United States)

    Chen, Mei-Ling; Shah, Vinod P; Ganes, Derek; Midha, Kamal K; Caro, James; Nambiar, Prabu; Rocci, Mario L; Thombre, Avinash G; Abrahamsson, Bertil; Conner, Dale; Davit, Barbara; Fackler, Paul; Farrell, Colm; Gupta, Suneel; Katz, Russell; Mehta, Mehul; Preskorn, Sheldon H; Sanderink, Gerard; Stavchansky, Salomon; Temple, Robert; Wang, Yaning; Winkle, Helen; Yu, Lawrence

    2010-09-01

    Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland. The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products. In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and inter-changeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/ response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product. The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and

  20. Development of a rational scale to assess the harm of drugs of potential misuse.

    Science.gov (United States)

    Nutt, David; King, Leslie A; Saulsbury, William; Blakemore, Colin

    2007-03-24

    Drug misuse and abuse are major health problems. Harmful drugs are regulated according to classification systems that purport to relate to the harms and risks of each drug. However, the methodology and processes underlying classification systems are generally neither specified nor transparent, which reduces confidence in their accuracy and undermines health education messages. We developed and explored the feasibility of the use of a nine-category matrix of harm, with an expert delphic procedure, to assess the harms of a range of illicit drugs in an evidence-based fashion. We also included five legal drugs of misuse (alcohol, khat, solvents, alkyl nitrites, and tobacco) and one that has since been classified (ketamine) for reference. The process proved practicable, and yielded roughly similar scores and rankings of drug harm when used by two separate groups of experts. The ranking of drugs produced by our assessment of harm differed from those used by current regulatory systems. Our methodology offers a systematic framework and process that could be used by national and international regulatory bodies to assess the harm of current and future drugs of abuse.

  1. Communication Regulatory Science: Mapping a New Field.

    Science.gov (United States)

    Noar, Seth M; Cappella, Joseph N; Price, Simani

    2017-12-13

    Communication regulatory science is an emerging field that uses validated techniques, tools, and models to inform regulatory actions that promote optimal communication outcomes and benefit the public. In the opening article to this special issue on communication and tobacco regulatory science, we 1) describe Food and Drug Administration (FDA) regulation of tobacco products in the US; 2) introduce communication regulatory science and provide examples in the tobacco regulatory science realm; and 3) describe the special issue process and final set of articles. Communication research on tobacco regulatory science is a burgeoning area of inquiry, and this work advances communication science, informs and potentially guides the FDA, and may help to withstand legal challenges brought by the tobacco industry. This research has the potential to have a major impact on the tobacco epidemic and population health by helping implement the most effective communications to prevent tobacco initiation and increase cessation. This special issue provides an example of 10 studies that exemplify tobacco regulatory science and demonstrate how the health communication field can affect regulation and benefit public health.

  2. Drug Facts

    Medline Plus

    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  5. FDA's requirements for radiation dosimetry of radiopharmaceutical drug products

    International Nuclear Information System (INIS)

    Abel, N.M.

    1986-01-01

    The primary concern of the Office of Drug Research and Review of the Food and Drug Administration in the field of radiation dosimetry is to ensure that radiopharmaceutical drug products are safe when used as investigational drugs (INDs) and are both safe and effective when a new drug application (NDA) is approved. In order to accomplish this, the sponsor of either an IND or applicant in the case of NDA must provide information that clearly describes the radiation dose that a patient will receive from the administration of the drug. The submitted numerical estimates of the radiation dose should be based on an absorbed fraction method of radiation dose calculation, such as the system set forth by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine or the system set forth by the International Commission on Radiological Protection (ICRP). This presentation will describe in detail the data that a sponsor of an IND needs to submit to satisfy the regulatory requirements. Examples will be given of common mistakes and omissions by sponsors in their presentation of data

  6. Regulatory control of nuclear power plants

    International Nuclear Information System (INIS)

    2002-01-01

    The purpose of this book is to support IAEA training courses and workshops in the field of regulatory control of nuclear power plants as well as to support the regulatory bodies of Member States in their own training activities. The target group is the professional staff members of nuclear safety regulatory bodies supervising nuclear power plants and having duties and responsibilities in the following regulatory fields: regulatory framework; regulatory organization; regulatory guidance; licensing and licensing documents; assessment of safety; and regulatory inspection and enforcement. Important topics such as regulatory competence and quality of regulatory work as well as emergency preparedness and public communication are also covered. The book also presents the key issues of nuclear safety such as 'defence-in-depth' and safety culture and explains how these should be taken into account in regulatory work, e.g. during safety assessment and regulatory inspection. The book also reflects how nuclear safety has been developed during the years on the basis of operating experience feedback and results of safety research by giving topical examples. The examples cover development of operating procedures and accident management to cope with complicated incidents and severe accidents to stress the importance of regulatory role in nuclear safety research. The main target group is new staff members of regulatory bodies, but the book also offers good examples for more experienced inspectors to be used as comparison and discussion basis in internal workshops organized by the regulatory bodies for refreshing and continuing training. The book was originally compiled on the basis of presentations provided during the two regulatory control training courses in 1997 and 1998. The textbook was reviewed at the beginning of the years 2000 and 2002 by IAEA staff members and consistency with the latest revisions of safety standards have been ensured. The textbook was completed in the

  7. Future nuclear regulatory challenges. A report by the NEA Committee on Nuclear Regulatory Activities

    International Nuclear Information System (INIS)

    1998-01-01

    Future challenges are considered that may arise from technical, socio-economic and political issues; organizational, management and human aspects; and international issues. The perceived challenges have been grouped into four categories, each covered by a chapter. Technical issues are addressed that many present regulatory challenges in the future: ageing nuclear power plants. External changes to industry are considered next that have an effect on regulators, privatization, cost reduction consequences, commercialization etc. It is followed by the impacts of internal changes: organizational, managerial, human-resources, licensing, staff training etc. Finally, international issues are discussed with potential regulatory impact. (R.P.)

  8. The NBOMe hallucinogenic drug series: Patterns of use, characteristics of users and self-reported effects in a large international sample.

    Science.gov (United States)

    Lawn, Will; Barratt, Monica; Williams, Martin; Horne, Abi; Winstock, Adam

    2014-08-01

    The NBOMe compounds are a novel series of hallucinogenic drugs that are potent agonists of the 5-HT2A receptor, have a short history of human consumption and are available to buy online, in most countries. In this study, we sought to investigate the patterns of use, characteristics of users and self-reported effects. A cross-sectional anonymous online survey exploring the patterns of drug use was conducted in 2012 (n = 22,289), including questions about the use of 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe and comparison drugs. We found that 2.6% of respondents (n = 582) reported having ever tried one of the three NBOMe drugs and that at 2.0%, 25I-NBOMe was the most popular (n = 442). Almost all (93.5%) respondents whose last new drug tried was a NBOMe drug, tried it in 2012, and 81.2% of this group administered the drug orally or sublingually/buccally. Subjective effects were similar to comparison serotonergic hallucinogens, though higher 'negative effects while high' and greater 'value for money' were reported. The most common (41.7%) drug source was via a website. The NBOMe drugs have emerged recently, are frequently bought using the internet and have similar effects to other hallucinogenic drugs; however, they may pose larger risks, due to the limited knowledge about them, their relatively low price and availability via the internet. © The Author(s) 2014.

  9. Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014).

    Science.gov (United States)

    Oelke, Matthias; Becher, Klaus; Castro-Diaz, David; Chartier-Kastler, Emmanuel; Kirby, Mike; Wagg, Adrian; Wehling, Martin

    2015-09-01

    we aimed to systematically review drugs to treat lower urinary tract symptoms (LUTS) regularly used in older persons to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability by using the Fit fOR The Aged (FORTA) classification. to evaluate the efficacy, safety and tolerability of drugs used for treatment of LUTS in older persons, a systematic review was performed. Papers on clinical trials and summaries of individual product characteristics were analysed regarding efficacy and safety in older persons (≥65 years). The most frequently used drugs were selected based on current prescription data. An interdisciplinary international expert panel assessed the drugs in a Delphi process. for the 16 drugs included here, a total of 896 citations were identified; of those, only 25 reported clinical trials with explicit data on, or solely performed in older people, underlining the lack of evidence in older people for drug treatment of LUTS. No drug was rated at the FORTA-A-level (indispensable). Only three were assigned to FORTA B (beneficial): dutasteride, fesoterodine and finasteride. The majority was rated FORTA C (questionable): darifenacin, mirabegron, extended release oxybutynin, silodosin, solifenacin, tadalafil, tamsulosin, tolterodine and trospium. FORTA D (avoid) was assigned to alfuzosin, doxazosin, immediate release oxybutynin, propiverine and terazosin. dutasteride, fesoterodine and finasteride were classified as beneficial in older persons or frail elderly people (FORTA B). For most drugs, in particular those from the group of α-blockers and antimuscarinics, use in this group seems questionable (FORTA C) or should be avoided (FORTA D). © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. 78 FR 49530 - Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics; Public Workshop

    Science.gov (United States)

    2013-08-14

    ...] Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics; Public Workshop AGENCY: Food and Drug... for Drug Evaluation and Research, in cosponsorship with the American College of Gastroenterology, the... American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, and the Pediatric IBD...

  11. 76 FR 18165 - Request for Public Comments Concerning Regulatory Cooperation Activities That Would Help...

    Science.gov (United States)

    2011-04-01

    ... DEPARTMENT OF COMMERCE International Trade Administration Request for Public Comments Concerning Regulatory Cooperation Activities That Would Help Eliminate or Reduce Unnecessary Regulatory Divergences in... ``Help'' tab.) All comments and recommendations submitted in response to this notice will be made...

  12. Risk undermined in the bilateral pharmaceutical regulatory system in Taiwan.

    Science.gov (United States)

    Wang, Hui-Po; Wang, Chun-Li

    2018-04-01

    The concept of Pharmacovigilance Planning and Risk Minimization Planning (PVP/RMP), initiated by the International Conference on Harmonization (ICH), addressed an important conceptual change from monitoring the safety of individual medicine to proactively conducting risk prevention for the minimization of medication error. However, the implementation of PVP/RMP is a challenge in societies like Taiwan where irrational medication and co-medication is prevalent. It is even more difficult in Taiwan where two regulatory bodies are governing pharmaceutical affairs, namely Taiwan Food and Drug Administration (TFDA) in charge of Western Medicine (WM) and the Department of Chinese Medicine and Pharmacy (DCMP) in charge of Traditional Chinese Medicine (TCM). There are thus dual-tract drug approval panels, two GMP controls and two independent adverse drug event reporting systems. This rendered irrational co-medication of WM and TCM undetectable and the standard tools for monitoring pharmacovigilance inapplicable. The bilateral regulatory system is conceptually unscientific in accordance with PVP/RMP and unethical from humanity point of view. The first part of this review delivers (1) social aspects of polypharmacy in Taiwan; (2) regulatory aspects of pharmaceutical administration; (3) risks undermined in the bilateral regulatory system and (4) pharmacoepidemiology in relation to the risk of polypharmacy. As evidence-based medicine (EBM) forms the fundamental risk-benefit assessment on medication, the second part of this review delivers (1) the scientific aspects of the beauty and the odds of biological system that governs host-xenobiotics interaction; (2) conceptual evolution from product management (pharmacovigilance) to risk management (PVP/RMP); (3) non-biased due process is essential for risk-benefit assessment on medicinal products and (4) the opinion of the authors on system building for safe medication. Copyright © 2018. Published by Elsevier B.V.

  13. Quantitative decisions in drug development

    CERN Document Server

    Chuang-Stein, Christy

    2017-01-01

    This book offers a high-level treatise of evidence-based decisions in drug development. Because of the inseparable relationship between designs and decisions, a good portion of this book is devoted to the design of clinical trials. The book begins with an overview of product development and regulatory approval pathways. It then discusses how to incorporate prior knowledge into study design and decision making at different stages of drug development. The latter include selecting appropriate metrics to formulate decisions criteria, determining go/no-go decisions for progressing a drug candidate to the next stage and predicting the effectiveness of a product. Lastly, it points out common mistakes made by drug developers under the current drug-development paradigm. The book offers useful insights to statisticians, clinicians, regulatory affairs managers and decision-makers in the pharmaceutical industry who have a basic understanding of the drug-development process and the clinical trials conducted to support dru...

  14. 78 FR 14306 - International Cooperation on Harmonisation of Technical Requirements for Registration of...

    Science.gov (United States)

    2013-03-05

    ...]; (Formerly Docket No. 00D-1631)] International Cooperation on Harmonisation of Technical Requirements for... for veterinary use by the International Cooperation on Harmonisation of Technical Requirements for... regulatory authorities and industry associations to promote the international harmonization of regulatory...

  15. 76 FR 57060 - International Cooperation on Harmonisation of Technical Requirements for Registration of...

    Science.gov (United States)

    2011-09-15

    ...] International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal... veterinary use by the International Cooperation on Harmonisation of Technical Requirements for Registration... regulatory authorities and industry associations to promote the international harmonization of regulatory...

  16. 78 FR 14308 - International Cooperation on Harmonisation of Technical Requirements for Registration of...

    Science.gov (United States)

    2013-03-05

    ...] International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal... been developed for veterinary use by the International Cooperation on Harmonisation of Technical... regulatory authorities and industry associations to promote the international harmonization of regulatory...

  17. Switzerland; Financial Sector Assessment Program: Factual Update: Insurance Sector Market and Regulatory Developments

    OpenAIRE

    International Monetary Fund

    2007-01-01

    This paper presents a factual update of the Insurance Core Principles including insurance sector market and regulatory developments for Switzerland. Regulatory reforms since 2003 have updated Switzerland’s regulatory and supervisory regime for the insurance industry to bring it in line with international best practices. The Insurance Supervision Law (ISL) has reoriented the regulatory focus and expanded the regulatory scope to include group/conglomerate supervision, corporate governance, risk...

  18. Regulatory risk coherence

    International Nuclear Information System (INIS)

    Remick, F.J.

    1992-01-01

    As one of the most progressive users of risk assessment in decision making, the US Nuclear Regulatory Commission (NRC) is in a position to play an important role in influencing the development of standard government wide policies for the application of risk assessment in decision making. The NRC, with the support of the nuclear industry, should use the opportunity provided by its experience with risk assessment to actively encourage the adoption of standard national and international health-based safety goals and at the same time accelerate its own efforts to implement the safety goals it has already developed for itself. There are signs of increased recognition of the need for consistency and coherence in the application of risk assessment in government decision making. The NRC and the nuclear industry have recently taken a great step toward establishing a consistant and coherent risk assessment-based culture in the US nuclear industry. As a result of Generic Letter 88-20, which asks each commercial nuclear power plant licensee to perform an individual plant examination by September 1992, for the first time a risk assessment characterizing initiating events in each plant will exist

  19. Regulatory control of radiation sources in Slovakia

    International Nuclear Information System (INIS)

    Auxtova, L.

    2001-01-01

    In Slovakia, there are two regulatory authorities. Regulatory control of the utilization of nuclear energy, based on the Slovak National Council's law No. 130/1998 on the peaceful uses of nuclear energy, is exercised by the Nuclear Regulatory Authority of the Slovak Republic. The second regulatory authority - the Ministry of Health - is empowered by law No. 72/1994 on the protection of human health to license radiation sources and is responsible for radiation protection supervision (there are nearly 3000 establishments with sealed sources, radiation generators and unsealed sources in Slovakia). Pursuant to a new radiation protection regulation based on international standards, radiation sources are to be categorized in six classes according to the associated exposure and contamination hazards. A national strategy for improving the safety of radiation sources over their life-cycle and for the management of disused and orphan sources is being prepared for governmental approval. (author)

  20. Regulatory Hybridization in the Transnational Sphere

    DEFF Research Database (Denmark)

    Kjær, Poul Fritz; Jurcys, Paulius; Yrakami, Ren

    Hybridization has become a defining feature of regulatory frameworks. The combined forces of globalization and privatization together with increased reliance on self-regulation have resulted in the emergence of a multitude of regulatory arrangements which combine elements from several legal orders....... This book offers a conceptual framework as well as numerous empirical explorations capable of increasing our understanding of regulatory hybridization. A number of central dichotomies are deconstructed: national vs. transnational law; international vs. transnational law; convergence vs. divergence; … read...... moresoft law vs. hard law; territorial vs. non-territorial, ‘top-down’ vs. ‘bottom-up’ globalization and national vs. global just as the implications of regulatory hybridization for the question of choice of court and conflict of laws are analyzed....

  1. Research and regulatory review

    International Nuclear Information System (INIS)

    Macleod, J.S.; Fryer, D.R.H.

    1979-01-01

    To enable the regulatory review to be effectively undertaken by the regulatory body, there is a need for it to have ready access to information generated by research activities. Certain advantages have been seen to be gained by the regulatory body itself directly allocating and controlling some portion of these activities. The princial reasons for reaching this conclusion are summarised and a brief description of the Inspectorates directly sponsored programme outlined. (author)

  2. Activities relating to PSA in the regulatory process

    International Nuclear Information System (INIS)

    Campbell, J.F.; Grint, G.C.

    1994-01-01

    In addition to the IAEA activities concerning the use of PSA in the regulatory process there are two other international initiatives in this area by the European Commission and the OECD's Committee for Nuclear Regulatory Authorities (CRNA). The paper gives a brief outline of these activities as well as introducing an update on the regulatory use of PSA in the UK. 3 refs, 3 tabs

  3. Nuclear Regulatory Authority of the Slovak Republic. Annual Report 2016

    International Nuclear Information System (INIS)

    2017-01-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2016 is presented. These activities are reported under the headings: Foreword by the Chairperson; (1) Legislative activities; (2) Regulatory Activities; (3) Nuclear safety of nuclear installations; (4) Nuclear Materials; (5) Competence of the building authority; (6) Emergency planning and preparedness; (7) International activities; (8) Public relations; (9) Nuclear Regulatory Authority of the Slovak Republic; (10) Annexes; (11) Abbreviations.

  4. The role of effective communications in Nuclear Regulatory Commission licensing

    International Nuclear Information System (INIS)

    Counsil, W.G.

    1991-01-01

    Communications are essential to the licensing and general regulatory program of the Nuclear Regulatory Commission. This paper attempts to identify and address certain aspects of, and approaches to, maintaining effective and efficient communications. It considers, from the perspective of the high-level radioactive waste repository program, both internal communication within the DOE itself and external communication with the Nuclear Regulatory Commission and interested parties. Many of the points presented are based on lessons learned from electric utility experience with nuclear plants

  5. Nuclear Regulatory Authority of the Slovak Republic. Annual Report 2013

    International Nuclear Information System (INIS)

    2014-04-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2013 is presented. These activities are reported under the headings: Foreword by the Chairperson; (1) Legislative activities; (2) Regulatory Activities; (3) Nuclear safety of nuclear power plants; (4) Nuclear Materials in SR; (5) Building Authority; (6) Emergency planning and preparedness; (7) International activities; (8) Public communication; (9) Nuclear Regulatory Authority of the Slovak Republic; (10) Annexes; (11) (12) Abbreviations.

  6. Nuclear Regulatory Authority of the Slovak Republic. Annual Report 2015

    International Nuclear Information System (INIS)

    2016-01-01

    A brief account of activities carried out by the Nuclear Regulatory Authority of the Slovak Republic (UJD SR) in 2015 is presented. These activities are reported under the headings: Foreword by the Chairperson; (1) Legislative activities; (2) Regulatory Activities; (3) Safety of nuclear installations; (4) Nuclear Materials; (5) Competence of the building authority; (6) Emergency planning and preparedness; (7) International activities; (8) Public relations; (9) Nuclear Regulatory Authority of the Slovak Republic; (10) Annexes; (11) Abbreviations.

  7. Regulatory Commission of Alaska

    Science.gov (United States)

    Map Help Regulatory Commission of Alaska Login Forgot Password Arrow Image Forgot password? View Cart login Procedures for Requesting Login For Consumers General Information Telephone Electric Natural Gas

  8. Mission Risk Reduction Regulatory Change Management

    Science.gov (United States)

    Scroggins, Sharon

    2007-01-01

    NASA Headquarters Environmental Management Division supports NASA's mission to pioneer the future in space exploration, scientific discovery, and aeronautics research by integrating environmental considerations into programs and projects early-on, thereby proactively reducing NASA's exposure to institutional, programmatic and operational risk. As part of this effort, NASA established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) as a resource for detecting, analyzing, and communicating environmental regulatory risks to the NASA stakeholder community. The RRAC PC focuses on detecting emerging environmental regulations and other operational change drivers that may pose risks to NASA programs and facilities, and effectively communicating the potential risks. For example, regulatory change may restrict how and where certain activities or operations may be conducted. Regulatory change can also directly affect the ability to use certain materials by mandating a production phase-out or restricting usage applications of certain materials. Regulatory change can result in significant adverse impacts to NASA programs and facilities due to NASA's stringent performance requirements for materials and components related to human-rated space vehicles. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented a system for proactively managing regulatory change to minimize potential adverse impacts to NASA programs and facilities. This presentation highlights the process utilized by the RRACPC to communicate regulatory change and the associated

  9. Drug Facts

    Medline Plus

    Full Text Available ... Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Videos Information About Drugs Alcohol ...

  10. Drug Allergy

    Science.gov (United States)

    ... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...

  11. Pilot study of essential drug quality in two major cities in India.

    Directory of Open Access Journals (Sweden)

    Roger Bate

    Full Text Available BACKGROUND: India is an increasingly influential player in the global pharmaceutical market. Key parts of the drug regulatory system are controlled by the states, each of which applies its own standards for enforcement, not always consistent with others. A pilot study was conducted in two major cities in India, Delhi and Chennai, to explore the question/hypothesis/extent of substandard and counterfeit drugs available in the market and to discuss how the Indian state and federal governments could improve drug regulation and more importantly regulatory enforcement to combat these drugs. METHODOLOGY/PRINCIPAL FINDINGS: Random samples of antimalarial, antibiotic, and antimycobacterial drugs were collected from pharmacies in urban and peri-urban areas of Delhi and Chennai, India. Semi-quantitative thin-layer chromatography and disintegration testing were used to measure the concentration of active ingredients against internationally acceptable standards. 12% of all samples tested from Delhi failed either one or both tests, and were substandard. 5% of all samples tested from Chennai failed either one or both tests, and were substandard. Spatial heterogeneity between pharmacies was observed, with some having more or less substandard drugs (30% and 0% respectively, as was product heterogeneity, with some drugs being more or less frequently substandard (12% and 7% respectively. CONCLUSIONS/SIGNIFICANCE: In a study using basic field-deployable techniques of lesser sensitivity rather than the most advanced laboratory-based techniques, the prevalence of substandard drugs in Delhi and Chennai is confirmed to be roughly in accordance with the Indian government's current estimates. However, important spatial and product heterogeneity exists, which suggests that India's substandard drug problem is not ubiquitous, but driven by a subset of manufacturers and pharmacies which thrive in an inadequately regulated environment. It is likely that the drug regulatory

  12. Pilot Study of Essential Drug Quality in Two Major Cities in India

    Science.gov (United States)

    Bate, Roger; Tren, Richard; Mooney, Lorraine; Hess, Kimberly; Mitra, Barun; Debroy, Bibek; Attaran, Amir

    2009-01-01

    Background India is an increasingly influential player in the global pharmaceutical market. Key parts of the drug regulatory system are controlled by the states, each of which applies its own standards for enforcement, not always consistent with others. A pilot study was conducted in two major cities in India, Delhi and Chennai, to explore the question/hypothesis/extent of substandard and counterfeit drugs available in the market and to discuss how the Indian state and federal governments could improve drug regulation and more importantly regulatory enforcement to combat these drugs. Methodology/Principal Findings Random samples of antimalarial, antibiotic, and antimycobacterial drugs were collected from pharmacies in urban and peri-urban areas of Delhi and Chennai, India. Semi-quantitative thin-layer chromatography and disintegration testing were used to measure the concentration of active ingredients against internationally acceptable standards. 12% of all samples tested from Delhi failed either one or both tests, and were substandard. 5% of all samples tested from Chennai failed either one or both tests, and were substandard. Spatial heterogeneity between pharmacies was observed, with some having more or less substandard drugs (30% and 0% respectively), as was product heterogeneity, with some drugs being more or less frequently substandard (12% and 7% respectively). Conclusions/Significance In a study using basic field-deployable techniques of lesser sensitivity rather than the most advanced laboratory-based techniques, the prevalence of substandard drugs in Delhi and Chennai is confirmed to be roughly in accordance with the Indian government's current estimates. However, important spatial and product heterogeneity exists, which suggests that India's substandard drug problem is not ubiquitous, but driven by a subset of manufacturers and pharmacies which thrive in an inadequately regulated environment. It is likely that the drug regulatory system in India needs

  13. Structural characterization of product ions by electrospray ionization and quadrupole time-of-flight mass spectrometry to support regulatory analysis of veterinary drug residues in foods Part 2: Benzimidazoles nitromidaz.....

    Science.gov (United States)

    RATIONALE: Analysis for identification and quantification of regulated veterinary drug residues in foods are usually achieved by liquid chromatography coupled to tandem mass spectrometry. The instrument method requires the selection of characteristic ions, but structure elucidation is seldom perform...

  14. International cooperation

    International Nuclear Information System (INIS)

    1996-01-01

    In 1995, Nuclear Regulatory Authority of the Slovak Republic (NRA SR) ensured foreign cooperation particularly in the frame of the Slovak Republic is membership in the IAEA, as well as cooperation with the Nuclear Energy Agency of the Organization for Economic Cooperation and Development (OECD NEA), cooperation with European Union in the frame of PHARE programmes, and intergovernmental cooperation and cooperation among nuclear regulatory authorities. With respect to an international importance, prestige and a wide-scope possibilities of a technical assistance , either a direct one (expert assessments, technology supplies, work placement, scientific trips, training courses) or indirect one (participation at various conferences, seminars, technical committees, etc), the most important cooperation with the IAEA in Vienna. In 1994, the Slovak Republic, was elected to the Board Governors, the represent the group of Eastern European countries. The Slovak Government entrusted the NRA SR's Chairman with representing the Slovak Republic in the Board of Governors. Owing to a good name of Slovakia was elected to the one of two Vice-Chairmen of the Board of Governors at the 882-nd session on the Board. IAEA approved and developed 8 national projects for Slovakia in 1995. Generally, IAEA is contracting scientific contracts with research institutes, nuclear power plants and other organizations. Slovak organizations used these contracts as complementary funding of their tasks. In 1995, there were 12 scientific contracts in progress, or approved respectively. Other international activities of the NRA SR, international co-operations as well as foreign affairs are reported

  15. Availability of and access to orphan drugs: an international comparison of pharmaceutical treatments for pulmonary arterial hypertension, Fabry disease, hereditary angioedema and chronic myeloid leukaemia.

    Science.gov (United States)

    Blankart, Carl Rudolf; Stargardt, Tom; Schreyögg, Jonas

    2011-01-01

    Market authorization does not guarantee patient access to any given drug. This is particularly true for costly orphan drugs because access depends primarily on co-payments, reimbursement policies and prices. The objective of this article is to identify differences in the availability of orphan drugs and in patient access to them in 11 pharmaceutical markets: Australia, Canada, England, France, Germany, Hungary, the Netherlands, Poland, Slovakia, Switzerland and the US. Four rare diseases were selected for analysis: pulmonary arterial hypertension (PAH), Fabry disease (FD), hereditary angioedema (HAE) and chronic myeloid leukaemia (CML). Indicators for availability were defined as (i) the indications for which orphan drugs had been authorized in the treatment of these diseases; (ii) the application date; and (iii) the date upon which these drugs received market authorization in each country. Indicators of patient access were defined as (i) the outcomes of technology appraisals; (ii) the extent of coverage provided by healthcare payers; and (iii) the price of the drugs in each country. For PAH we analysed bosentan, iloprost, sildenafil, treprostinil (intravenous and inhaled) as well as sitaxentan and ambrisentan; for FD we analysed agalsidase alfa and agalsidase beta; for HAE we analysed icatibant, ecallantide and two complement C1s inhibitors; for CML we analysed imatinib, dasatinib and nilotinib. Most drugs included in this study had received market authorization in all countries, but the range of indications for which they had been authorized differed by country. The broadest range of indications was found in Australia, and the largest variations in indications were found for PAH drugs. Authorization process speed (the time between application and market authorization) was fastest in the US, with an average of 362 days, followed by the EU (394 days). The highest prices for the included drugs were found in Germany and the US, and the lowest in Canada, Australia and

  16. Use of fluorogestone acetate sponges or controlled internal drug release for estrus synchronization in ewes: Effects of hormonal profiles and reproductive performance.

    Science.gov (United States)

    Swelum, Ayman Abdel-Aziz; Alowaimer, Abdullah Nasser; Abouheif, Mohamed Ahmed

    2015-09-01

    This study was carried out using 300 multiparous Najdi ewes during breeding season to compare the effects of fluorogestone acetate (FGA) sponges and controlled internal drug release (CIDR) dispensers to synchronize estrus on reproductive performance and hormonal profiles. Ewes were equally and randomly allotted into group A (FGA) and group B (CIDR); intravaginal progestagen was administered for 14-day period with intramuscular administration of 600-IU eCG at withdrawal time. Estrus was detected using a vasectomized ram starting 12 hours after progestagen withdrawal and repeated every 12 hours up to 84 hours. Blood samples were collected at the time of progestagen withdrawal (0 hour), 24 hours, and 48 hours. Follicle-stimulating hormone, LH, estradiol, and progesterone serum concentrations were measured using commercial ELISA kits and microtitrimetric plates. Timed laparoscopic insemination was performed 48 hours after progestagen withdrawal. Pregnancy and the number of fetuses were diagnosed by ultrasonography on Day 23 after insemination and confirmed on Days 35 and 60. The results revealed that the retention, vaginal discharge, and drawstring breakage rates after progestagen removal were significantly (P ≤ 0.05) higher in the FGA group (94.00, 98.58, and 9.22, respectively) than those in the CIDR group. On the other hand, pregnancy, fertility, twinning rates, and fecundity were significantly (P ≤ 0.05) higher in the CIDR group (77.86, 75.57, 34.34, and 1.02, respectively) than in the FGA group. Estrus responses in FGA and CIDR groups increased gradually to attain their significantly (P ≤ 0.05) higher percentages after 48 hours of progestagen withdrawal (91.49 and 92.37, respectively); thereafter, they decreased. The overall estrus responses and prolificacy did not differ between the FGA and CIDR groups. Follicle-stimulating hormone was significantly higher in the FGA group at 24 and 48 hours after progestagen withdrawal, whereas LH was significantly higher

  17. Manipulation of reproductive seasonality using melatonin implantation in Anglo-Nubian does treated with controlled internal drug release and equine chorionic gonadotropin during the nonbreeding season.

    Science.gov (United States)

    El-Mokadem, M Y; El-Din, A N M Nour; Ramadan, T A; Rashad, A M A; Taha, T A; Samak, M A

    2017-06-01

    The objective of this study was to compare the efficiency of hormonal treatments on ovarian activity and reproductive performance in anestrous Anglo-Nubian does during the nonbreeding season (February to May). A total of 48 multiparous does were divided into 2 groups (24 lactating does and 24 dry does). In each group, animals were allocated randomly into 2 equal subgroups (12 does each). In the first subgroup, does received a single 18-mg melatonin implant for 42 d followed by a controlled internal drug release (CIDR) device for 19 d in conjunction with 500 IU of equine chorionic gonadotropin (eCG) i.m. on the day of CIDR device removal. The second subgroup received CIDR combined with eCG in parallel with the first subgroup. Melatonin implantation induced a luteotrophic effect, expressed as an increasing number of corpora lutea, increased serum progesterone concentration, and reduced estradiol concentration. Regardless of treatment, dry does showed greater value of progesterone concentration. With the advancement of day of treatment, number of total follicles, small follicles, and medium follicles tended to increase to the greatest values at the day of CIDR device insertion. Furthermore, at day of mating, the numbers of large follicles reached the greatest value, which was associated with the lowest value of the number of corpora lutea. At day of mating, serum progesterone concentration achieved the lowest value, which increased until d 56 of pregnancy. The estradiol:progesterone ratio showed the opposite trend. The detrimental effect of reproductive seasonality, expressed as cessation of estrus behavior and fertile mating during the nonbreeding season, was successfully alleviated by the CIDR-eCG protocol. Furthermore, melatonin implantation in conjunction with the CIDR-eCG protocol enhanced conception rate and fecundity at d 28 of pregnancy and prolificacy at d 56 of pregnancy compared with does that were not implanted. Interestingly, does that failed to conceive

  18. US Nuclear Regulatory Commission 1983 annual report

    International Nuclear Information System (INIS)

    1984-01-01

    The thirteen chapters of this annual report are titled: 1983 highlights/1984 planning; reactor regulation; cleanup at TMI-2; operational experience; nuclear materials; safeguards; waste management; inspection, enforcement and emergency preparedness; cooperation with the states; international programs; nuclear regulatory research; proceedings and litigation; and management and communication

  19. Developing legal regulatory frameworks for modern biotechnology ...

    African Journals Online (AJOL)

    This paper looks at attempts that have been made to develop legal regulatory frameworks for modern biotechnology. The discussion is limited to the regulation of Genetically Modified Organisms (GMO) technology by the two leading producers and exporters of GMOs in Africa: South Africa and Kenya. The international and ...

  20. US Nuclear Regulatory Commission annual report, 1985. Volume 2

    International Nuclear Information System (INIS)

    1986-01-01

    The decisions and actions of the Nuclear Regulatory Commission (NRC) during fiscal year 1985 are reported. Areas covered include reactor regulation, cleanup at Three Mile Island, analysis and evaluation of operational experience, nuclear materials, waste management, safeguards, inspection, enforcement, quality assurance, emergency preparedness, and nuclear regulatory research. Also, cooperation with the states, international programs, proceedings and litigation, and management are discussed

  1. Multi-regional clinical trials and global drug development

    Directory of Open Access Journals (Sweden)

    Premnath Shenoy

    2016-01-01

    Full Text Available Drug development has been globalized, and multi-regional clinical trial (MRCT for regulatory submission has widely been conducted by many discovery based global pharmaceutical companies with the objective of reducing the time lag of launch in key markets and improve patient access to new and innovative treatments. Sponsors are facing several challenges while conducting multiregional clinical trials. Challenges under the heads statistics, clinical, regulatory operational, and ethics have been discussed. Regulators in different countries such as USA, EU-Japan, and China have issued guidance documents in respect of MRCT's. Lack of harmonization in the design and planning of MRCT is perceived to create a difficult situation to sponsors adversely affecting progressing MRCT in more and more discoveries. International conference on hormonisation (ICH has initiated the process for having a harmonized guidance document on MRCT. This document is likely to be issued in early 2017.

  2. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-10-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  3. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  4. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-01-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  5. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1991-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  6. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-08-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  7. Trust in regulatory regimes

    NARCIS (Netherlands)

    Six, Frédérique; Verhoest, Koen

    2017-01-01

    Within political and administrative sciences generally, trust as a concept is contested, especially in the field of regulatory governance. This groundbreaking book is the first to systematically explore the role and dynamics of trust within regulatory regimes. Conceptualizing, mapping and analyzing

  8. 76 FR 9028 - Training Program for Regulatory Project Managers; Information Available to Industry

    Science.gov (United States)

    2011-02-16

    ...] Training Program for Regulatory Project Managers; Information Available to Industry AGENCY: Food and Drug... Duvall-Miller, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire... to provide the following: (1) Firsthand exposure to industry's drug development processes and (2) a...

  9. 75 FR 10806 - Training Program for Regulatory Project Managers; Information Available to Industry

    Science.gov (United States)

    2010-03-09

    ...] Training Program for Regulatory Project Managers; Information Available to Industry AGENCY: Food and Drug... INFORMATION CONTACT: Beth Duvall-Miller, Center for Drug Evaluation and Research, Food and Drug Administration... to provide the following: (1) First hand exposure to industry's drug development processes and (2) a...

  10. 77 FR 10538 - Training Program for Regulatory Project Managers; Information Available to Industry

    Science.gov (United States)

    2012-02-22

    ...] Training Program for Regulatory Project Managers; Information Available to Industry AGENCY: Food and Drug... Brum, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave...) Firsthand exposure to industry's drug development processes and (2) a venue for sharing information about...

  11. 78 FR 8544 - Training Program for Regulatory Project Managers; Information Available to Industry

    Science.gov (United States)

    2013-02-06

    ...] Training Program for Regulatory Project Managers; Information Available to Industry AGENCY: Food and Drug... Brum, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave... to industry's drug development processes and (2) a venue for sharing information about project...

  12. Improving nuclear regulatory effectiveness

    International Nuclear Information System (INIS)

    2001-01-01

    Ensuring that nuclear installations are operated and maintained in such a way that their impact on public health and safety is as low as reasonably practicable has been and will continue to be the cornerstone of nuclear regulation. In the past, nuclear incidents provided the main impetus for regulatory change. Today, economic factors, deregulation, technological advancements, government oversight and the general requirements for openness and accountability are leading regulatory bodies to review their effectiveness. In addition, seeking to enhance the present level of nuclear safety by continuously improving the effectiveness of regulatory bodies is seen as one of the ways to strengthen public confidence in the regulatory systems. This report covers the basic concepts underlying nuclear regulatory effectiveness, advances being made and future requirements. The intended audience is primarily nuclear safety regulators, but government authorities, nuclear power plant operators and the general public may also be interested. (author)

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... WMATA) Dallas Area Rapid Transit (DART) NY Metropolitan Transportation Authority (MTA) Titan Worldwide Hestia International Panasonic Times ... Education Projects National Drug & Alcohol Facts Week NIDA ...

  14. Comparisons of Food and Drug Administration and European Medicines Agency risk management implementation for recent pharmaceutical approvals: report of the International Society for Pharmacoeconomics and outcomes research risk benefit management working group.

    Science.gov (United States)

    Lis, Yvonne; Roberts, Melissa H; Kamble, Shital; J Guo, Jeff; Raisch, Dennis W

    2012-12-01

    1) To compare the Food and Drug Administration's (FDA's) Risk Evaluation and Mitigation Strategies (REMS) and European Medicines Agency's (EMA's) Risk Management Plan (RMP) guidances and 2) to compare REMS and RMPs for specific chemical entities and biological products. FDA, EMA, and pharmaceutical company Web sites were consulted for details pertaining to REMS and RMPs. REMS requirements include medication guides, communication plans, elements to ensure safe use, implementation systems, and specified assessment intervals. RMP requirements are increased pharmacovigilance and risk minimization activities. We compared these requirements for drugs requiring both REMS and RMPs. We identified 95 drugs on FDA's REMS list as of March 2010. Of these, there were 29 drugs (11 biologics and 18 new chemical entities) with EMA RMPs. REMS and RMPs are similar in objectives, with comparable toolkits. Both allow flexibility in product-specific actions, recognizing adverse effects of potential concern. Of the 29 drugs reviewed, REMS requirements not included in RMPs were patient medication guides (100% of the drugs), provider communication plans (38%), and routine monitoring of REMS (66%). RMP requirements not included in REMS were specific adverse event reporting (45% of the drugs), prospective registry studies (34%), prospective epidemiology studies (24%), additional trial data (28%), and Summary of Product Characteristics contraindications (76%). Both REMS and RMPs provide positive guidance for identification, monitoring, and minimization of risk to patient safety. Currently, neither agency provides specific guidance on how risk should be related to benefit either qualitatively or quantitatively. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  15. Regulatory framework and safety requirements for new (gen III) reactors

    International Nuclear Information System (INIS)

    Mourlon, Sophie

    2014-01-01

    Sophie Mourlon, ASN Deputy General Director, described the international process to enhance safety between local safety authorities through organizations such as WENRA. Then she explained to the participants the regulatory issues for the next generation of NPPs

  16. Comparison of Fiscal and Regulatory Policies to Prevent Non ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    India is facing a rising burden of cardiovascular disease and obesity-related diabetes ... As a result, fiscal and regulatory strategies such as food taxes have been ... International Water Resources Association, in close collaboration with IDRC, ...

  17. Even Giants Need A Club: Domestic Institutions, Market Size, And Regulatory Influence

    OpenAIRE

    DAVID BACH

    2005-01-01

    This paper show that work on international market regulation has paid insufficient attention to the critical role played by domestic political and regulatory institutions. Existing literature emphasizes the role of market power, determined by market size, in analyzing international regulatory influence. While we do not contest the importance of market power, we introduce the notion of domestic regulatory capacity to capture the domestic institutional side of international market regulation th...

  18. Do the recommended standards for in vitro biopharmaceutic classification of drug permeability meet the "passive transport" criterion for biowaivers?

    Science.gov (United States)

    Žakelj, Simon; Berginc, Katja; Roškar, Robert; Kraljič, Bor; Kristl, Albin

    2013-01-01

    BCS based biowaivers are recognized by major regulatory agencies. An application for a biowaiver can be supported by or even based on "in vitro" measurements of drug permeability. However, guidelines limit the application of biowaivers to drug substances that are transported only by passive mechanisms. Regarding published permeability data as well as measurements obtained in our institution, one can rarely observe drug substances that conform to this very strict criterion. Therefore, we measured the apparent permeability coefficients of 13 drugs recommended by FDA's Guidance to be used as standards for "in vitro" permeability classification. The asymmetry of permeability data determined for both directions (mucosal-to-serosal and serosalto- mucosal) through the rat small intestine revealed significant active transport for four out of the nine high-permeability standards and for all four low-permeability standard drugs. As could be expected, this asymmetry was abolished at 4°C on rat intestine. The permeability of all nine high-permeability, but none of the low permeability standards, was also much lower when measured with intestinal tissue, Caco-2 cell monolayers or artificial membranes at 4°C compared to standard conditions (37°C). Additionally, concurrent testing of several standard drugs revealed that membrane transport can be affected by the use of internal permeability standards. The implications of the results are discussed regarding the regulatory aspects of biopharmaceutical classification, good practice in drug permeability evaluation and regarding the general relevance of transport proteins with broad specificity in drug absorption.

  19. The management of cytotoxic drug wastes in Shiraz, Iran: an overview of all government and private chemotherapy settings, and comparison with national and international guidelines.

    Science.gov (United States)

    Askarian, Mehrdad; Momeni, Mohsen; Danaei, Mina

    2013-06-01

    Excessive use of cytotoxic drugs owing to a dramatic increase in malignancy incidence leads to the production of high amounts of cytotoxic wastes. In Iran, management of hazardous wastes has been neglected in recent decades. The aim of this study was to determine the amount of intravenous cytotoxic drug wastes, their collection and disposal status in chemotherapy wards, and to compare the current status with standard guidelines in Shiraz, Iran. This cross-sectional study was performed using data collected during 2 consecutive months, from 22 June to 22 August 2011, in all 13 chemotherapy wards in Shiraz. The amount of prescribed drugs, drugs waste, collection and disposal status of cytotoxic drugs were recorded. We then compared the current status of waste collection and disposal in our samples with our national guideline. The prescription of cytotoxic drugs and the amount of total drugs waste reached approximately 6 and 0.2 kilograms respectively. Total vials volume was calculated to be approximately 1000 l in order to estimate the volume of containers required for the encapsulation method. The results demonstrated that the current status of cytotoxic waste collection and disposal is inappropriate, and none of the facilities under study followed our guidelines perfectly. The adherence to all recommendations and guidelines was poorer in private wards than in government-run ones. The management of cytotoxic wastes is inappropriate and our existing national guidelines are lacking. Suggestions for the best management of cytotoxic waste are revising the existing guidelines, allocating a sufficient budget, training healthcare workers, providing multiple administration options of cytotoxic drugs and accomplishing a surveillance system.

  20. Global Banking System Regulatory Environment

    Directory of Open Access Journals (Sweden)

    Oleh Mozhovyi

    2017-03-01

    Full Text Available The international and domestic experience shows that the main factors of financial destabilization during the financial crises are in the banking sector. The article reveals that the vulnerability of the financial system is connected with functions, deposit and credit transactions, risks distribution and ensuring liquidity; banks act as a major factor in stabilisation measures in the current context of globalization processes, since the economic stability of banking activities relates directly to all the entities and only stable banking system can withstand the crisis phenomena. Therefore, as a result of the analysis, it is proved that not only reduction of risks of banks is needed, but also introduction of the effective supervision system over implementation of the requirements and standards to prevent these risks. According to modern international approaches, banks use the so-called prudential supervision, which is based on the risk management assessment policy on the part of the Bank’s management, and regulatory bodies contribute to implementation of such policy. The authors have concluded that not only modern specificity of banks, but also the impact of supervision systems and regulation of modern trends in development of the banking should be analysed. Application of the general regulatory principles and banking risks methodology is required. The task of supervision is distribution of reliable risk management practices in the banking system, taking into account national peculiarities of development.