WorldWideScience

Sample records for products regulatory agency

  1. 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...

  2. Assistance to Oil and Gas State Agencies and Industry through Continuation of Environmental and Production Data Management and a Water Regulatory Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Grunewald, Ben; Arthur, Dan; Langhus, Bruce; Gillespie, Tom; Binder, Ben; Warner, Don; Roberts, Jim; Cox, D.O.

    2002-05-31

    This grant project was a major step toward completion of the Risk Based Data Management System (RBDMS) project. Additionally the project addresses the needs identified during the projects initial phases. By implementing this project, the following outcomes were sought: (1) State regulatory agencies implemented more formalized environmental risk management practices as they pertain to the production of oil and gas, and injection via Class II wells. (2) Enhancement of oil and gas production by implementing a management system supporting the saving of abandoned or idle wells located in areas with a relatively low environmental risk of endangering underground sources of drinking water (USDWs) in a particular state. (3) Verification that protection of USDWs is adequate and additional restrictions of requirements are not necessary in areas with a relatively low environmental risk. (4) Standardization of data and information maintained by state regulatory agencies and decrease the regulatory cost burden on producers operating in multiple states, and (5) Development of a system for electronic data transfer among operators and state regulatory agencies and reduction of overall operator reporting burdens.

  3. Regulatory Powers in Public Procurement Law of Peruvian Administrative Agencies

    Directory of Open Access Journals (Sweden)

    Juan Carlos Morón Urbina

    2017-12-01

    Full Text Available Peruvian law has explicitly recognized regulatory powers to administrative agencies, which allows them to have a preponderant role in the production of rules in public procurement. Although these delegations of legislative authority are positively defined, distortions in the system of legal sources arise when agencies exceed delegated powers or when measures issued by administrative entities are mistaken for regulations. This paper aims to identify regulatory powers of Peruvian administrative agencies, as well as the regulatory measures they issue, and their relation with other sources of law.

  4. Information resources in state regulatory agencies-a California perspective

    Energy Technology Data Exchange (ETDEWEB)

    DiZio, S.M. [California Environmental Protection Agency, Sacramento (United States)

    1990-12-31

    Various state regulatory agencies have expressed a need for networking with information gatherers/researchers to produce a concise compilation of primary information so that the basis for regulatory standards can be scientifically referenced. California has instituted several programs to retrieve primary information, generate primary information through research, and generate unique regulatory standards by integrating the primary literature and the products of research. This paper describes these programs.

  5. Environmental Protection Agency Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... of the economy, productivity, competition, jobs, the environment, public health or safety, or State... Steve Fruh, Environmental Protection Agency, Air and Radiation, 1200 Pennsylvania Ave, NW, Washington, DC 20460 Phone: 919 541-2837 Fax: 919 541-4991 Email: fruh.steve@epamail.epa.gov RIN: 2060-AP69...

  6. Politically Induced Regulatory Risk and Independent Regulatory Agencies

    OpenAIRE

    Strausz, Roland

    2015-01-01

    Uncertainty in election outcomes generates politically induced regulatory risk. Political parties' risk attitudes towards such risk depend on a fluctuation effect that hurts both parties and an output--expansion effect that benefits at least one party. Notwithstanding the parties' risk attitudes, political parties have incentives to negotiate away all regulatory risk by pre-electoral bargaining. Efficient pre-electoral bargaining outcomes fully eliminate politically induced regulatory risk. P...

  7. Strategy for communicating benefit-risk decisions: a comparison of regulatory agencies' publicly available documents.

    Science.gov (United States)

    Leong Wai Yeen, James; Salek, Sam; Walker, Stuart

    2014-01-01

    The assessment report formats of four major regulatory reference agencies, US Food and Drug Administration, European Medicines Agency, Health Canada, and Australia's Therapeutic Goods Administration were compared to a benefit-risk (BR) documentation template developed by the Centre for Innovation in Regulatory Science and a four-member Consortium on Benefit-Risk Assessment. A case study was also conducted using a US FDA Medical Review, the European Public Assessment Report and Australia's Public Assessment Report for the same product. Compared with the BR Template, existing regulatory report formats are inadequate regarding the listing of benefits and risks, the assigning of relative importance and values, visualization and the utilization of a detailed, systematic, standardized structure. The BR Template is based on the principles of BR assessment common to major regulatory agencies. Given that there are minimal differences among the existing regulatory report formats, it is timely to consider the feasibility of a universal template.

  8. Regulatory Science in Practice (Pharmaceuticals and Medical Devices Agency).

    Science.gov (United States)

    Hojo, Taisuke

    2017-01-01

    Review, safety, and relief services of the Pharmaceuticals and Medical Devices Agency are primarily focused on scientifically evaluating pharmaceuticals, medical devices, and cellular and tissue-based products referring to their quality, efficacy, and safety, which requires a variety of scientific knowledge and methods. Pharmaceutical regulation should be established based on the most advanced scientific expertise at all times. In order to evaluate products that use cutting-edge technology such as induced pluripotent stem cells and information and communication technology adequately, since fiscal year 2012 the Science Committee has been established as a platform to exchange opinions among members from top-ranking domestic and international academia and to enhance personnel exchanges through the Initiative to Facilitate Development of Innovative Drugs. In addition, the Regulatory Science Center will be established in 2018 to increase the integrity of our services for product reviews and safety measures. In particular, requiring electronic data submissions for clinical trial applications followed by an advanced approach to analysis should not only enhance the quality of reviews of individual products but should also support the development of pharmaceuticals and medical devices by providing pharmaceutical affairs consultations on research and development strategies with various guidelines based on new insights resulting from product-bridging data analysis. Moreover, a database including electronic health records with comprehensive medical information collected mainly from 10 cooperating medical institutions will be developed with the aim of developing safety measures in a more timely manner using methods of pharmacoepidemiological analysis.

  9. Knowledge Management Implementation In Indonesia Nuclear Energy Regulatory Agency (BAPETEN)

    International Nuclear Information System (INIS)

    Nurwidi Astuti, Y.H.

    2016-01-01

    Full text: Indonesian Nuclear Energy Regulatory Agency (BAPETEN) acquires the task and function to control the safety, security and safeguards in the field of nuclear energy through the development of legislation, licensing services, inspection and enforcement. Which is supported by review and assessment, emergency preparedness. Knowledge Management (KM) is importance for BAPETEN to achieve the Regulatory body effectiveness and product innovation. The Chairman of BAPETEN has set policies statement for KM implementation. To implement a knowledge management program, BAPETEN creates KM guidelines that includes blueprint and roadmap KM programme based on a KM readiness survey. The KM readiness survey involves 20% of staff who represent each unit and discussions with the senior manager of BAPETEN, and the result of readiness survey produce 13 KM BAPETEN initiatives strategic. After the initiative strategic has been obtained, BAPETEN creates the Roadmap of BAPETEN Knowledge Management for 2015–2019 programme for KM People with the activity sozialization of KM Guidebook, workshop SMART knowledge worker, nurture Community of practices (COP) and develop social network analysis (SNE). KM Process with activity focus group discussion, KM Readyness survey, KM Statement, KM Bapeten Guidebook, knowledge mapping, knowledge harvesting. KM Technology with activity develop knowledge system or portal, e-learning. (author

  10. Safety Culture Implementation in Indonesian Nuclear Energy Regulatory Agency (BAPETEN)

    International Nuclear Information System (INIS)

    Nurwidi Astuti, Y.H.; Dewanto, P.

    2016-01-01

    The Indonesia Nuclear Energy Act no. 10 of 1997 clearly stated that Nuclear Energy Regulatory Agency (BAPETEN) is the Nuclear Regulatory Body. This is the legal basis of BAPETEN to perform regulatory functions on the use of nuclear energy in Indonesia, including regulation, authorisation, inspection and enforcement. The Independent regulatory functions are stipulated in Article 4 and Article 14 of the Nuclear Energy Act no. 10 (1997) which require the government to establish regulatory body that is reporting directly to the president and has responsibility to control of the use of nuclear energy. BAPETEN has been start fully its functioning on January 4, 1999. In it roles as a regulatory body, the main aspect that continues and always to be developed is the safety culture. One of the objectives of regulatory functions is “to increase legal awareness of nuclear energy of the user to develop safety culture” (Article 15, point d), while in the elucidation of article 15 it is stipulated that “safety culture is that of characteristics and attitudes in organizations and individual that emphasise the importance of safety”.

  11. Survey of regulatory agency review of generating unit performance

    International Nuclear Information System (INIS)

    Roach, E.M. Jr.; Tarletz, D.B.

    1985-01-01

    Regulatory agencies across the country are being called upon increasingly to monitor the management of electric utilities. Such activity, which once was relatively rare, is now common. Most frequently this oversight centers around the operating performance of generating units, both nuclear and fossil. There are, perhaps, several reasons for this increased interest in the efficient operation of generating units: increased fuel costs and fuel cost differentials, increased lead times and costs for construction of new generating units, and increased dependence on existing units because of construction programs being revised to meet decreased load growth. The monitoring of generating units has taken the form of after the fact evaluation of performance on a case-by-case basis and the implementation of productivity incentive programs. Performance standards are used in these contexts both to measure the adequacy of unit performance and to implement incentives in the form of rewards or penalties. The standard used may be a subjective test of prudent performance or some numerical index of plant performance, e.g., equivalent availability, capacity factor or heat rate. Some of the activity by regulators is reviewed in applying subjective and numerical standards and the considerations involved in applying such standards are discussed

  12. Decisions by regulatory agencies: are they evidence-based?

    Directory of Open Access Journals (Sweden)

    Furberg Curt D

    2007-04-01

    Full Text Available Abstract Contradictory statements about the non-steroidal anti-inflammatory drugs from the European Medicines Agency and the United States Food and Drug Administration have raised questions about whether regulatory decisions are evidence-based. For the selective COX-2 inhibitors, there are clear contraindications and warnings in Europe, but only a vaguely worded Black Box warning in the United States. All the non-selective agents are given an almost "clean bill of health" in Europe, while all of them are judged to have a similar risk-benefit ratio as celecoxib in the United States. The regulatory agencies have failed to recognize the clinical trial evidence that the risk of cardiovascular events varies substantially among the non-selective agents, with diclofenac carrying the highest risk of harm.

  13. Bioremediation, regulatory agencies and public acceptance of this technology

    International Nuclear Information System (INIS)

    Westlake, D. W. S.

    1997-01-01

    The technology of bioremediation, i.e. the utilization of microorganisms to degrade environmental pollutants, the dangers and consequences inherent in the large-scale use of microbial organisms in such processes, and the role of regulatory agencies in the utilization and exploitation of bioremediation technologies, were discussed. Factors influencing public acceptance of bioremediation as a satisfactory tool for cleaning up the environment vis-a-vis other existing and potential rehabilitation techniques were also reviewed. The ambiguity of regulatory agencies in the matter of bioremediation was noted. For example, there are many regulatory hurdles relative to the testing, use and approval of transgenic microorganisms for use in bioremediation. On the other hand, the use and release of engineered plants is considered merely another form of hybrid and their endorsement is proceeding rapidly. With regard to public acceptance, the author considered bioremediation technology as too recent, with not enough successful applications to attract public attention. Although the evidence suggests that bioremediation is environmentally safe, the efficacy, reliability and predictability of the various technologies have yet to be demonstrated. 25 refs

  14. Modernizing the Regulatory System for Biotechnology Products

    Science.gov (United States)

    This Web page describes the continuing effort to modernize the federal regulatory system for biotechnology products as well as clarify various roles of EPA, FDA and USDA in evaluating new biotechnology products.

  15. 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.

  16. 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

  17. Culture, Product Advertising, and Advertising Agency Operations ...

    African Journals Online (AJOL)

    Culture, Product Advertising, and Advertising Agency Operations. ... As a means of telling the market about a new product, advertising persuades and reminds the audience of their continuous support of the ... AJOL African Journals Online.

  18. Isotope production technologies from a regulatory perspective

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, K. [Canadian Nuclear Safety Committee, Ottawa, Ontario (Canada)

    2012-07-01

    This paper discusses isotope production technologies from a regulatory perspective. The regulator is the CNSC which has the mandate to protect the health, safety and security of persons and the environment and to implement Canada's international commitments on the peaceful use of nuclear energy. Nuclear facilities regulated by CNSC include linear accelerator (medical), pool irradiator (industrial) and Pelletron (research) as well as cyclotrons.

  19. 75 FR 54917 - Criteria for Nominating Materials Licensees for the U.S. Nuclear Regulatory Commission's Agency...

    Science.gov (United States)

    2010-09-09

    ... NUCLEAR REGULATORY COMMISSION [NRC-2010-0294] Criteria for Nominating Materials Licensees for the U.S. Nuclear Regulatory Commission's Agency Action Review Meeting AGENCY: Nuclear Regulatory Commission. ACTION: Request for comment. SUMMARY: It is the policy of the U.S. Nuclear Regulatory Commission...

  20. National Strategy for Modernizing the Regulatory System for Biotechnology Products

    Science.gov (United States)

    This National Strategy for Modernizing the Regulatory System for Biotechnology Products sets forth a vision for ensuring that the federal regulatory system is prepared to efficiently assess the risks, if any, of the future products of biotechnology.

  1. Court-agency interaction in environmental policymaking: the cases of the Nuclear Regulatory Commission and the Environmental Protection Agency

    International Nuclear Information System (INIS)

    Thomas, L.W.

    1981-01-01

    This study examines the increasingly active participation of courts in the administrative process as well as agency responses to court-imposed policy shifts. More specifically, it is an investigation of the interaction between the federal courts, primarily the Supreme Court and the District of Columbia Court of Appeals, and two federal regulatory agencies, the Nuclar Regulatory Commission and the Environmental Protection Agency. There are five objectives to the study. The first is to examine the natura of court-agency interaction and to determine the extent to which patterns of judicial review of administrative actions can be discerned. The second is to examine the effect of court orders on agency programs and policies. The third is to assess the anticipatory dimension of court-agency relations. The fourth is to inquire into the recurring dimension of court-agency interaction and to determine its effect on subsequent court decisions. The last is to assess the institutional capacity of courts to deal with scientific and technological issues. This study indicates that judicial review has a substantial effect on the NRC's and the EPA's decision-making activities. Few, if any, recent major policy decisions of the two agencies have not been scrutinized closely by federal appellate courts. During the past decade, the courts have blocked policy initiative on numerous occasions and have been the primary source of change in others. In addition, the mere anticipation of judicial review was found to be a factor motivating the two agencies to make reasoned decisions

  2. 77 FR 12896 - Self-Regulatory Organizations; Midwest Clearing Corporation; Order Cancelling Clearing Agency...

    Science.gov (United States)

    2012-03-02

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66458; File No. 600-9] Self-Regulatory Organizations; Midwest Clearing Corporation; Order Cancelling Clearing Agency Registration February 24, 2012. I... Act provides that in the event any self- regulatory organization is no longer in existence or has...

  3. 77 FR 12898 - Self-Regulatory Organizations; Midwest Securities Trust Company; Order Cancelling Clearing Agency...

    Science.gov (United States)

    2012-03-02

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66461; File No. 600-7] Self-Regulatory Organizations; Midwest Securities Trust Company; Order Cancelling Clearing Agency Registration February 24, 2012... the event any self-regulatory organization is no longer in existence or has ceased to do business in...

  4. Formal independence of regulatory agencies and Varieties of Capitalism

    DEFF Research Database (Denmark)

    Guardiancich, Igor; Guidi, Mattia

    2016-01-01

    The Varieties of Capitalism literature posits that national economic institutions reflect the mode of coordination of a country’s market actors. Despite the importance of this claim and a rich literature on the emergence of regulatory capitalism, few studies test such prediction for Independent...

  5. 76 FR 41585 - Regulation and Independent Regulatory Agencies

    Science.gov (United States)

    2011-07-14

    ... permitted by law, such decisions should be made only after consideration of their costs and benefits (both... concerning public participation, integration and innovation, flexible approaches, and science. To the extent... public a plan, consistent with law and reflecting its resources and regulatory priorities and processes...

  6. 78 FR 66940 - Regulatory Requirements for Hearing Aid Devices and Personal Sound Amplification Products; Draft...

    Science.gov (United States)

    2013-11-07

    ... for such products. These inconsistent interpretations of the definitions may inadvertently result in... amplification products (PSAPs), as well as the regulatory controls that apply to each. This draft guidance is... of clarity regarding how the Agency defines a hearing aid versus a personal sound amplification...

  7. Independent regulatory agencies and rules harmonization for the electricity sector and renewables in the Mediterranean region

    International Nuclear Information System (INIS)

    Cambini, Carlo; Franzi, Donata

    2013-01-01

    The paper analyses the existing regulatory framework for the electricity and renewables sectors, and the role of regulatory agencies in Northern Africa and Middle East countries, under the promotion by the European Union. Using data collected through an original survey directed at regulators, ministry departments and energy companies of the southern Mediterranean, the study is aimed at assessing the extent of agencies' independence looking at three main dimensions of independence: regulatory instruments available to regulators and decision making autonomy; regulators' organizational autonomy; and regulators accountability. Results show that those countries having established an independent regulator have a more credible regulatory framework than those countries in which such a body does not exist. In particular, the analysis shows that Turkey, Croatia and Jordan have defined a regulatory framework that limits administrative expropriation and, consequently, creates an environment more suitable for attracting investments in the electricity and renewables sector. On the institutional ground, this is probably related with the harmonization of regulatory standards promoted by the European Union through the neighboring policy, for the Jordan case, and the membership perspective, in the Turkish and Croatian cases. - Highlights: • We analyze the existing regulatory framework in Northern Africa and Middle East countries. • We construct an original dataset through a survey directed to national regulators. • The extent of agencies' independence has been assessed in different dimensions. • These dimensions are decision making autonomy; organizational autonomy; and accountability. • Few countries have defined a regulatory framework limiting administrative expropriation

  8. Relationship between Saskatchewan government regulatory agencies and the oil and gas industry

    International Nuclear Information System (INIS)

    Lechner, L.J.; Mathieson, B.

    1998-01-01

    The roles and responsibilities of various government agencies as they interact with the oil and gas industry in Saskatchewan were described. The regulatory agencies featured in this paper were Saskatchewan Energy and Mines (SEM), Saskatchewan Environment and Resource Management (SERM), and Saskatchewan Agriculture and Food (SAF). The management of land sales, seismic activities, exploration and oil and gas production activities were reviewed. While each of the agencies has a different mandate, they have a common goal regarding petroleum resources, and that is to ensure that the oil and gas industry carries out its activities in a sustainable manner while protecting and conserving the environment. The mandate of SEM is to facilitate the discovery, development and use of Saskatchewan's energy and mineral resources. SERM's mandate is to manage, enhance and protect Saskatchewan's natural and environmental resources such as fish, wildlife, lands, forests, parks, air, water and soil, for conservation, recreation, social and economic purposes. The mandate of SAF is to manage crown land in the province and to control surface access to these lands

  9. Sustainability, natural and organic cosmetics: consumer, products, efficacy, toxicological and regulatory considerations

    Directory of Open Access Journals (Sweden)

    Bruno Fonseca-Santos

    2015-03-01

    Full Text Available The interest in sustainable products has increased along the years, since the choice of products, packaging and production processes have a great impact on the environment. These products are classified by regulatory agencies in different categories, aggregating advantages to the product and increasing the demand by consumers. However, there is no harmonization in guidelines of these certifying agencies and each cosmetic industry formulates their product and packaging in a more rational way, which causes less damage to the environment. Many cosmetic products have in their formulation natural products that perform a specific biological function, but these products should be evaluated on efficacy and toxicological aspects. The aim of this article is to approach sustainability, natural and organic cosmetics, considering the consumer and the efficacy, toxicological and regulatory aspects.

  10. A regulatory review for products containing glutathione

    Directory of Open Access Journals (Sweden)

    Nur Hidayah Abd Rahim

    2016-01-01

    Full Text Available Glutathione is a potent antioxidant as well as has important role for DNA synthesis and repair, protein synthesis, amino acid transport, and enzyme activation. Besides this, Glutathione products are now mainly selling as whitening agent which are mainly marketing through social media (Facebook and different websites. Information is not available whether glutathione product are following the regulatory guidelines of National Pharmaceutical Control Bureau of Malaysia (NPCB for selling, advertisement and promotion. This review was carried out by extracting information about glutathione from scientific database using PubMed, Cochrane Library and Embase. Analysis of the available information, case example of glutathione products showed that a brand of glutathione (Glutacaps HQ did not show the product's registration number from NPCB, and also did not show the name, address, contact number of the advertiser, and even not found the name of the manufacture. Without providing the above mentioned information, the product is selling and promoting through social media (fb which is not allowed by the NPCB guidelines part 4.14. So far, only two clinical trials were conducted on glutathione supplementation for 4 weeks duration. There was no serious or systematic adverse effects reported in clinical trials. As the two clinic trials resulted contradictory outcomes, further studies needed for conformation of the clinic benefits of glutathione. Otherwise, random use of glutathione may be risk for the health of the people. Besides, the marketer mainly promoting glutathione as the skin whitening beauty product instead of using as health supplement, it may cause additional and serious risk to the users as the manufacturer not providing sufficient information about the product, its registration number, manufacturing company, etc.

  11. Bureaucratic Minimal Squawk Behavior: Theory and Evidence from Regulatory Agencies

    OpenAIRE

    Clare Leaver

    2009-01-01

    This paper argues that bureaucrats are susceptible to `minimal squawk` behavior. I develop a simple model in which a desire to avoid criticism can prompt, otherwise public-spirited, bureaucrats to behave inefficiently. Decisions are taken to keep interest groups quiet and mistakes out of the public eye. The policy implications of this behavior are at odds with the received view that agencies should be structured to minimise the threat of `capture`. I test between theories of bureaucratic beha...

  12. 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.

  13. Survey of extreme load design regulatory agency licensing requirements for nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Stevenson, J D

    1976-04-01

    Since 1965, when extreme load requirements began to be considered explicitly in nuclear power plant design, there has been a gradual divergence in requirements imposed by national regulatory agencies. However, nuclear plant safety is an international problem because of the potential international effects of any postulated plant failure. For this reason this paper has been prepared in an attempt to highlight the differences in national criteria currently used in the extreme load design of nuclear plant facilities. No attempt has been made to evaluate the relative merit of the criteria established by the various national regulatory agencies. This paper presents the results of a recent survey made of national atomic energy regulatory agencies and major nuclear steam supply design agencies, which requested a summary of current licensing criteria associated with earthquake, extreme wind (tornado), flood, airplane crash and accident (pipe break) loads applicable within the various national jurisdictions. Also presented are a number of comparisons which are meant to illustrate the differences in national regulatory criteria.

  14. Survey of extreme load design regulatory agency licensing requirements for nuclear power plants

    International Nuclear Information System (INIS)

    Stevenson, J.D.

    1976-01-01

    Since 1965, when extreme load requirements began to be considered explicitly in nuclear power plant design, there has been a gradual divergence in requirements imposed by national regulatory agencies. However, nuclear plant safety is an international problem because of the potential international effects of any postulated plant failure. For this reason this paper has been prepared in an attempt to highlight the differences in national criteria currently used in the extreme load design of nuclear plant facilities. No attempt has been made to evaluate the relative merit of the criteria established by the various national regulatory agencies. This paper presents the results of a recent survey made of national atomic energy regulatory agencies and major nuclear steam supply design agencies, which requested a summary of current licensing criteria associated with earthquake, extreme wind (tornado), flood, airplane crash and accident (pipe break) loads applicable within the various national jurisdictions. Also presented are a number of comparisons which are meant to illustrate the differences in national regulatory criteria. (Auth.)

  15. Overview of the European Medicines Agency's Development of Product-Specific Bioequivalence Guidelines.

    Science.gov (United States)

    Sullivan, Jane O'; Blake, Kevin; Berntgen, Michael; Salmonson, Tomas; Welink, Jan

    2017-12-05

    The European Medicines Agency's (EMA) product-specific bioequivalence guidelines outline harmonized regulatory requirements for studies to demonstrate bioequivalence for products that may have particular needs due to their pharmacokinetics, in addition to those outlined in general guidance. As such they are potentially very useful to the pharmaceutical industry in the development of generic medicinal products and to regulatory authorities for harmonized decision-making. Since their introduction in 2013, EMA product-specific bioequivalence guidelines continue to increase in number, and as of June 2017, encompass a number of different pharmacotherapeutic groups and pharmaceutical forms. This article further elucidates the processes involved for stakeholders and reviews the Agency's experience with the development of these guidelines, including the scientific issues witnessed with their advancement. A comparison with the United States Food and Drug Administration approach to similar guidelines is also provided. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  16. A strategy for regulatory action when new adverse effects of a licensed product emerge.

    Science.gov (United States)

    Aronson, Jeffrey K; Price, Deirdre; Ferner, Robin E

    2009-01-01

    Regulatory agencies grant product licences (marketing authorizations) for medicinal products in the light of evidence that the balance between benefit and harm in the population is favourable. Here we consider a framework for allowing regulatory agencies to make rational decisions when reviewing product licences in the light of new information about harms that change that balance. The regulator can revoke the product licence, restrict the product's availability or change the 'label' in different ways. We examine the features of the adverse effect that may be relevant in making the decision: namely, individual differences in susceptibility; the possibility of monitoring; and the availability of protective strategies. The balance of benefit and harm, and the time-course and dose relation of the adverse effect play important roles in the decision-making process. We set out how these factors can help determine the logical response to new information on the balance between benefit and harm, and provide a series of relevant examples. We believe that when regulatory agencies have to decide how to amend the product licence of a drug when new serious adverse effects cause concern, they would find it useful to adopt a framework of this kind, using different strategies for different cases. Our proposed framework could also be useful in risk management planning during drug development.

  17. Guideline for regulatory agencies in evaluating contents of root cause analysis by operators

    International Nuclear Information System (INIS)

    Hata, Takaya; Makino, Maomi; Kosaka, Atsuhiko

    2008-01-01

    'Guideline for Regulatory Agencies in Evaluating Contents of Root cause Analysis by Operators' was enacted as the policy for new inspection system in Japan. The objective is to indicate the view point to verify the appropriateness of the corrective actions and preventive actions implemented by operators based on root cause analysis and its analysis results. This guideline is leading to take four points into special consideration for adequate application. They are encouragement of further activities of the operators, flexible interpretation of the intention, versatility of the analysis methods and concepts and consideration of no blame culture. Moreover, as view point for regulatory agencies, it indicates with special emphasis that neutrality of the analyzing party, objectivity of analysis result, and logicality of the analysis method are ensured. This guideline shall be continuously reviewed through integration of lessons learned from active use in future. (author)

  18. Driven by expertise and insulation?: the autonomy of European regulatory agencies

    OpenAIRE

    Ossege, Christoph

    2015-01-01

    Expertise and autonomy are cornerstones to the effective operation and legitimacy of European Regulatory Agencies (ERAs). Yet, we know little about ERAs' actual autonomy, nor about factors shaping it. This article studies ERAs' actual autonomy from public and private actors, emphasising two crucial explanatory factors: expertise and rulemaking competences. The lack of insights on expertise is particularly striking, as expertise -the "raison d'être" and main resource of expert bodies- provides...

  19. 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

  20. European regulatory tools for advanced therapy medicinal products.

    Science.gov (United States)

    Flory, Egbert; Reinhardt, Jens

    2013-12-01

    Increasing scientific knowledge and technical innovations in the areas of cell biology, biotechnology and medicine resulted in the development of promising therapeutic approaches for the prevention and treatment of human diseases. Advanced therapy medicinal products (ATMPs) reflect a complex and innovative class of biopharmaceuticals as these products are highly research-driven, characterised by innovative manufacturing processes and heterogeneous with regard to their origin, type and complexity. This class of ATMP integrates gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineering products and are often individualized and patient-specific products. Multiple challenges arise from the nature of ATMPs, which are often developed by micro, small and medium sized enterprises, university and academia, for whom regulatory experiences are limited and regulatory requirements are challenging. Regulatory guidance such as the reflection paper on classification of ATMPs and guidelines highlighting product-specific issues support academic research groups and pharmaceutical companies to foster the development of safe and effective ATMPs. This review provides an overview on the European regulatory aspects of ATMPs and highlights specific regulatory tools such as the ATMP classification procedure, a discussion on the hospital exemption for selected ATMPs as well as borderline issues towards transplants/transfusion products.

  1. Culture, Product Advertising, and Advertising Agency Operations

    African Journals Online (AJOL)

    gold

    2012-07-26

    Jul 26, 2012 ... market about a new product, advertising persuades and reminds the audience ... The relevance of this topic can also be shown by the true story of the Gerber ... product was the product; people thought they were being.

  2. The Environmental Protection Agency in the Early Trump Administration: Prelude to Regulatory Capture.

    Science.gov (United States)

    Dillon, Lindsey; Sellers, Christopher; Underhill, Vivian; Shapiro, Nicholas; Ohayon, Jennifer Liss; Sullivan, Marianne; Brown, Phil; Harrison, Jill; Wylie, Sara

    2018-04-01

    We explore and contextualize changes at the Environmental Protection Agency (EPA) over the first 6 months of the Trump administration, arguing that its pro-business direction is enabling a form of regulatory capture. We draw on news articles, public documents, and a rapid response, multisited interview study of current and retired EPA employees to (1) document changes associated with the new administration, (2) contextualize and compare the current pro-business makeover with previous ones, and (3) publicly convey findings in a timely manner. The lengthy, combined experience of interviewees with previous Republican and Democratic administrations made them valuable analysts for assessing recent shifts at the Scott Pruitt-led EPA and the extent to which these shifts steer the EPA away from its stated mission to "protect human and environmental health." Considering the extent of its pro-business leanings in the absence of mitigating power from the legislative branch, we conclude that its regulatory capture has become likely-more so than at similar moments in the agency's 47-year history. The public and environmental health consequences of regulatory capture of the EPA will probably be severe and far-reaching.

  3. Organizational behavior of regulatory agencies: a case study of the Bureau of Consumer Services in the Pennsylvania Public Utility Commission

    Energy Technology Data Exchange (ETDEWEB)

    Silver, J.H.

    1981-01-01

    Regulatory agencies operate in a complex field of organizations and interest groups. The variety of behaviors that occur in the regulatory field are not satisfactorily explained by current interpretative frameworks. Regulatory agencies are at once criticized and praised. They flourish as organizational entities, yet they exhibit behavior that is often inexplicable. Notions like clientele capture, the politics of regulation, exchange theory, and institutionalized organizations do not singly explain the vagaries of regulatory behavior. A merger of these viewpoints, however, provides a foundation for a comprehensive interpretative framework. A bureau of consumer services within a state public utility commission is viewed as an institutionalized organization. From this perspective, a variety of ritual behaviors, based upon symbolic and tangible interorganizational exchanges are observed and characterized. The outcome of these exchanges is the establishment of the Bureau of Consumer Services as a legitimate regulatory agent with significant impact upon the formulation of regulatory policy in the formal proceedings of the Pennsylvania Public Utility Commission.

  4. Driven by Expertise and Insulation? The Autonomy of European Regulatory Agencies

    Directory of Open Access Journals (Sweden)

    Christoph Ossege

    2015-03-01

    Full Text Available Expertise and autonomy are cornerstones to the effective operation and legitimacy of European Regulatory Agencies (ERAs. Yet, we know little about ERAs’ actual autonomy, nor about factors shaping it. This article studies ERAs’ actual autonomy from public and private actors, emphasising two crucial explanatory factors: expertise and rulemaking competences. The lack of insights on expertise is particularly striking, as expertise—the “raison d’être” and main resource of expert bodies—provides ERAs with a potentially powerful means to increase autonomy. Relying on a rational institutionalist framework within which ERAs enjoy substantive discretion to pursue their goals, the study empirically compares three powerful ERAs—the European Medicines Agency, the European Chemicals Agency, and the European Food Safety Authority. Based on the analysis of 39 semi-structured expert interviews, findings show that expertise is a crucial explanation for ERAs’ substantive autonomy from the Commission. Towards research intensive private stakeholders, the role of expertise becomes less pronounced. Instead, ERAs are more successful in protecting their autonomy by engaging in the risk-averse interpretation of the regulatory framework and by adapting rules over time to adapt their needs: they engage in “procedural insulation”. Political salience provides a scope condition for ERAs to use expert knowledge and rulemaking competences more strategically—potentially undermining scientific quality.

  5. Hazardous waste management system--Environmental Protection Agency. Notice of regulatory reform actions; request for comments.

    Science.gov (United States)

    1982-12-13

    In response to Executive Order 12291 and the President's Task Force on Regulatory Relief, the Environmental Protection Agency is reviewing and reassessing the hazardous waste regulations developed under the Resource Conservation and Recovery Act (RCRA). A variety of activities are underway that will simplify procedures and reduce paperwork, modify existing regulations to make them more workable and cost effective, and control new wastes and new processes. The purpose of this notice is to inform the public of these activities and invite comments on the general approaches being taken.

  6. Regulatory simplification of fission product chemistry

    International Nuclear Information System (INIS)

    Read, J.B.J.; Soffer, L.

    1986-01-01

    The requirements for design provisions intended to limit fission product escape during reactor accidents have been based since 1962 upon a small number of simply-stated assumptions. These assumptions permeate current reactor regulation, but are too simple to deal with the complex processes that can reasonably be expected to occur during real accidents. Potential chemical processes of fission products in severe accidents are compared with existing plant safety features designed to minimize off-site consequences, and the possibility of a new set of simply-stated assumptions to replace the 1982 set is discussed

  7. Defense Logistics Agency Product Quality Deficiency Program

    National Research Council Canada - National Science Library

    1998-01-01

    .... He was interested in improving the product quality deficiency report system, which is used by DoD Components to identify and purge nonconforming material from inventory and to provide information...

  8. Providing Value to New Health Technology: The Early Contribution of Entrepreneurs, Investors, and Regulatory Agencies

    Science.gov (United States)

    Lehoux, Pascale; Miller, Fiona A.; Daudelin, Geneviève; Denis, Jean-Louis

    2017-01-01

    Background: New technologies constitute an important cost-driver in healthcare, but the dynamics that lead to their emergence remains poorly understood from a health policy standpoint. The goal of this paper is to clarify how entrepreneurs, investors, and regulatory agencies influence the value of emerging health technologies. Methods: Our 5-year qualitative research program examined the processes through which new health technologies were envisioned, financed, developed and commercialized by entrepreneurial clinical teams operating in Quebec’s (Canada) publicly funded healthcare system. Results: Entrepreneurs have a direct influence over a new technology’s value proposition, but investors actively transform this value. Investors support a technology that can find a market, no matter its intrinsic value for clinical practice or healthcare systems. Regulatory agencies reinforce the "double" value of a new technology—as a health intervention and as an economic commodity—and provide economic worth to the venture that is bringing the technology to market. Conclusion: Policy-oriented initiatives such as early health technology assessment (HTA) and coverage with evidence may provide technology developers with useful input regarding the decisions they make at an early stage. But to foster technologies that bring more value to healthcare systems, policy-makers must actively support the consideration of health policy issues in innovation policy. PMID:28949463

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Cell therapy medicinal product regulatory framework in Europe and its application for MSC based therapy development

    Directory of Open Access Journals (Sweden)

    Janis eAncans

    2012-08-01

    Full Text Available Advanced therapy medicinal products (ATMPs, including cell therapy products, form a new class of medicines in the European Union. Since ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT has been established at European Medicines Agency (EMA for centralized classification, certification and evaluation procedures, and other ATMP related tasks. Guidance documents, initiatives and interaction platforms are available to make the new framework more accessible for small and medium-sized enterprises, academia, hospitals and foundations. Good understanding of centralised and national components of the regulatory system is required to plan product development. It is in the best interests of cell therapy developers to utilise provided resources starting with the preclinical stage. Whilst there have not been mesenchymal stem cell (MSC based medicine authorisations in the EU, three MSC products have received marketing approval in other regions since 2011. Information provided on regulatory requirements, procedures and initiatives is aimed to facilitate MSC based medicinal product development and authorisation in the EU.

  14. Production of GMP certified herbal products in Malaysian Nuclear Agency

    International Nuclear Information System (INIS)

    Daryl Jesus Arapoc; Bohari Yaacob; Zainah Adam

    2015-01-01

    This paper will discuss on up scaling production of herbal product. A pilot scale production plant were developed in Block 37 and equipped with automated and semi-automated production machines which have the capacity to produce 100 thousand pieces of tablet per hour. In order to ensure the quality of the products, raw material inspections, IPQC and FPQC will be done on each batch. Besides that, certification of GMP will be done concurrently. One of the products that will be launch soon is the Mas Cotek tablet. This product is the result of numerous years of researches that had been done in BTP. This includes formulation and production of the product itself. It is hope that more herbal products can be produce in near future. (author)

  15. Radioactivity in consumer products : radiation safety and regulatory appraisal

    International Nuclear Information System (INIS)

    Murthy, B.K.S.; Venkataraman, G.; Subrahmanym, P.

    1993-01-01

    Use of radioactive materials in consumer products is in vogue almost since the discovery of radioactivity. There has been a rapid growth in the use of radioactive material in various consumer products such as Ionization Chamber Smoke Detectors (ICSD), Static eliminators, etc. In addition, there are certain manufacturing processes wherein the Naturally Occurring Radioactive Material (NORM) get incorporated in the consumer products. Certain phosphatic fertilizers, titanium dioxide pigments, phospho gypsum plaster boards are some examples in this category. The manufacture and use of these products result in radiation dose to the public apart from radiation exposure to the personnel involved in the manufacturing process. Appropriate radiation control measures have to be taken in the design, manufacture and use of consumer products to ensure that the radiation doses to the public and the population at large do not exceed the relevant limits. While appropriate regulatory controls and surveillance are established for manufacture and use of certain products, these are still to be recognised and established in respect of certain other processes and products. The current status of radiation safety and regulatory control and the lack of these in respect of some products are discussed in this paper. (author). 5 refs

  16. Regulating Medicines in Croatia: Five-year Experience of Agency for Medicinal Products and Medical Devices

    Science.gov (United States)

    Tomić, Siniša; Filipović Sučić, Anita; Plazonić, Ana; Truban Žulj, Rajka; Macolić Šarinić, Viola; Čudina, Branka; Ilić Martinac, Adrijana

    2010-01-01

    Aim To present the activities of the Agency for Medicinal Products and Medical Devices in the first 5 years of its existence and to define its future challenges. Methods Main activities within the scope of the Agency as a regulatory authority were retrospectively analyzed for the period from 2004-2008. Data were collected from the Agency’s database and analyzed by descriptive statistics. Results The number of issued medicine authorizations rose from 240 in 2004 to 580 in 2008. The greatest number of new chemical and biological entities was approved in 2005. The greatest number of regular quality controls (n = 5833) and special quality controls was performed in 2008 (n = 589), while the greatest number of off-shelf quality controls (n = 132) was performed in 2007. The greatest number of medicine labeling irregularities was found in 2007 (n = 19) and of quality irregularities in 2004 (n = 9). The greatest number of adverse reactions was reported in 2008 (n = 1393). The number of registered medical devices rose from 213 in 2004 to 565 in 2008. Conclusion Over its 5 years of existence, the Agency has successfully coped with the constant increase in workload. In the future, as Croatia enters the European Union, the Agency will have to face the challenge of joining the integrated European regulatory framework. PMID:20401952

  17. Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective.

    Science.gov (United States)

    Salmikangas, Paula; Schuessler-Lenz, Martina; Ruiz, Sol; Celis, Patrick; Reischl, Ilona; Menezes-Ferreira, Margarida; Flory, Egbert; Renner, Matthias; Ferry, Nicolas

    2015-01-01

    With the release of Regulation 1394/2007, a new framework for gene and cell therapy medicinal products and tissue-engineered products was established in the European Union. For all three product classes, called advanced therapy medicinal products, a centralised marketing authorisation became mandatory. The European Medicines Agency (EMA) together with its Committee for Advanced Therapies, Committee for Human Medicinal Products and the network of national agencies is responsible for scientific evaluation of the marketing authorisation applications. For a new application, data and information relating to manufacturing processes and quality control of the active substance and the final product have to be submitted for evaluation together with data from non-clinical and clinical safety and efficacy studies. Technical requirements for ATMPs are defined in the legislation, and guidance for different products is available through several EMA/CAT guidelines. Due to the diversity of ATMPs, a tailored approach for regulating these products is considered necessary. Thus, a risk-based approach has been introduced for ATMPs allowing flexibility for the regulatory requirements. Since the regulatory framework for ATMPs was established, five products have been licenced in the European Union. However, the pipeline of new ATMPs is much bigger, as seen from the significant numbers of different products discussed by the CAT in scientific advice and classification procedures. In 2013, a public consultation on the ATMP Regulation was conducted by the European Commission, and the results were published in 2014. The report proposes several improvements for the current framework and established procedures for the regulation of ATMPs.

  18. Changing innovation into a registered product: From concept to regulatory approval.

    Science.gov (United States)

    Rhodes, Linda

    2018-05-01

    Innovation in animal health pharmaceuticals is important to address unmet and underserved medical needs, and often comes from products initially developed for human medicine. The purpose of the review is to help readers understand how breakthroughs from human biotechnology may be developed for use in veterinary medicine, while understanding the key drivers to success, the difficulties of regulatory approval, and the realistic risks and rewards of developing applications for animals. The types of human drugs which may be useful for veterinary applications are reviewed, including examples. The regulatory path is discussed, with a review of the various oversight agencies, and the categories of data required to be submitted, including safety, efficacy, manufacturing, environmental impact and human food safety. In conclusion, the cost, development time, and barriers to innovation in veterinary medical pharmaceuticals are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Toward a functional definition of a "rare disease" for regulatory authorities and funding agencies.

    Science.gov (United States)

    Clarke, Joe T R; Coyle, Doug; Evans, Gerald; Martin, Janet; Winquist, Eric

    2014-12-01

    The designation of a disease as "rare" is associated with some substantial benefits for companies involved in new drug development, including expedited review by regulatory authorities and relaxed criteria for reimbursement. How "rare disease" is defined therefore has major financial implications, both for pharmaceutical companies and for insurers or public drug reimbursement programs. All existing definitions are based, somewhat arbitrarily, on disease incidence or prevalence. What is proposed here is a functional definition of rare based on an assessment of the feasibility of measuring the efficacy of a new treatment in conventional randomized controlled trials, to inform regulatory authorities and funding agencies charged with assessing new therapies being considered for public funding. It involves a five-step process, involving significant negotiations between patient advocacy groups, pharmaceutical companies, physicians, and public drug reimbursement programs, designed to establish the feasibility of carrying out a randomized controlled trial with sufficient statistical power to show a clinically significant treatment effect. The steps are as follows: 1) identification of a specific disease, including appropriate genetic definition; 2) identification of clinically relevant outcomes to evaluate efficacy; 3) establishment of the inherent variability of measurements of clinically relevant outcomes; 4) calculation of the sample size required to assess the efficacy of a new treatment with acceptable statistical power; and 5) estimation of the difficulty of recruiting an adequate sample size given the estimated prevalence or incidence of the disorder in the population and the inclusion criteria to be used. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  20. Regulatory structures for gene therapy medicinal products in the European Union.

    Science.gov (United States)

    Klug, Bettina; Celis, Patrick; Carr, Melanie; Reinhardt, Jens

    2012-01-01

    Taking into account the complexity and technical specificity of advanced therapy medicinal products: (gene and cell therapy medicinal products and tissue engineered products), a dedicated European regulatory framework was needed. Regulation (EC) No. 1394/2007, the "ATMP Regulation" provides tailored regulatory principles for the evaluation and authorization of these innovative medicines. The majority of gene or cell therapy product development is carried out by academia, hospitals, and small- and medium-sized enterprises (SMEs). Thus, acknowledging the particular needs of these types of sponsors, the legislation also provides incentives for product development tailored to them. The European Medicines Agency (EMA) and, in particular, its Committee for Advanced Therapies (CAT) provide a variety of opportunities for early interaction with developers of ATMPs to enable them to have early regulatory and scientific input. An important tool to promote innovation and the development of new medicinal products by micro-, small-, and medium-sized enterprises is the EMA's SME initiative launched in December 2005 to offer financial and administrative assistance to smaller companies. The European legislation also foresees the involvement of stakeholders, such as patient organizations, in the development of new medicines. Considering that gene therapy medicinal products are developed in many cases for treatment of rare diseases often of monogenic origin, the involvement of patient organizations, which focus on rare diseases and genetic and congenital disorders, is fruitful. Two such organizations are represented in the CAT. Research networks play another important role in the development of gene therapy medicinal products. The European Commission is funding such networks through the EU Sixth Framework Program. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. The Independence of the Media and Its Regulatory Agencies: Shedding new light on formal and actual independence against the national context

    NARCIS (Netherlands)

    Schultz, W.; Valcke, P.; Irion, K.

    2014-01-01

    Media independence is vital for democracies, and so is the independence of the regulatory bodies governing it. The Independence of the Media and its Regulatory Agencies explores the complex relationship between media governance and independence of media regulatory authorities within Europe, which

  2. Regulatory and clinical aspects of psychotropic medicinal products bioequivalence.

    Science.gov (United States)

    Bałkowiec-Iskra, Ewa; Cessak, Grzegorz; Kuzawińska, Olga; Sejbuk-Rozbicka, Katarzyna; Rokita, Konrad; Mirowska-Guzel, Dagmara

    2015-07-01

    Introduction of generic medicinal products to the market has increased access to modern therapies but also enabled significant reduction in their cost, leading to containment of public expenditures on medicinal products reimbursement. The critical assessment of bioequivalence of any reference medicinal product and its counterpart is based on comparison of their rate and extent of absorption. It is assumed that two medicinal products are bioequivalent when their rate and extent of absorption do not show significant differences when administered at the same dose under similar experimental conditions. Bioequivalent medicinal products are declared to be also therapeutically equivalent and can be used interchangeably. However, despite regulatory declaration, switching from reference to generic drugs is often associated with concerns of healthcare providers about decreased treatment effectiveness or occurrence of adverse drug reactions. The aim of this article is to provide a description of rules that guide registration of generic medicinal products in the European Union and to analyze specific examples from the scientific literature concerning therapeutic equivalence of reference and generic antidepressant and antipsychotic medicinal products. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  3. Regulatory requirements for the use of consumer products containing radioactive substances

    International Nuclear Information System (INIS)

    Mason, G.C.; Paynter, R.A.; Schmitt-Hannig, A.; Sztanyik, L.B.

    1996-01-01

    In almost 100 years since the discovery of radioactivity, the properties of radioactive materials have been exploited in products such as clocks and watches incorporating luminous paint which are freely available to members of the public. Over time, regulatory authorities have felt it necessary to apply some degree of control to the supply and use of such products in order to protect public health. In many areas of radiation protection, national authorities take note of international recommendations when developing national standards, but the existing detailed guidance of the International Atomic Energy Agency (IAEA) for consumer products is incomplete and out of date. Recently, a thorough revision of the International Basic Safety Standards (BSS) has occurred, which has prompted a review and revision of the related guidance published by the IAEA. A draft Guide on Regulatory Requirements for the Use of Consumer Products Containing Radioactive Substances has now been completed and is currently under review within the IAEA's system for development of documents in its Safety Series of publications. (author)

  4. DEVELOPMENT OF TECHNOLOGY AND REGULATORY DOCUMENTATION ON PROCESSED BROCCOLI PRODUCT

    Directory of Open Access Journals (Sweden)

    T. I. Kryachko

    2017-01-01

    Full Text Available The aim of the present investigation was development of an efficient technology for obtaining powders from fresh broccoli; determination of the possibility of using domestic production of broccoli as an import-substituting product; development of regulatory documentation for broccoli powders for the food industry. The research was carried out jointly with the representatives of the Federal Scientific cen-ter of vegetable production on an experimental basis in 2016. The domestic Tonus variety of broccoli (Federal Scientific center of vegetable production and the Maraton F1 hybrid (France, differing in appearance, vegetative period, biochemical and physical characteristics were chosen. Technology of broccoli powder production from domestic and imported products was developed using two methods of drying convection and lyophilization. The gentle drying conditions of broccoli freeze drying compared to convective drying technology provided higher content of both vitamin C and polyphenols in the final powder. Comparative studies of organoleptic and physico-chemical properties of powders obtained from domestic and imported broccoli demonstrated close quality parameters, indicating the possibility of effective domestic broccoli utilization and import substitution. For the first time in the Russian Federation, the "Organization Standard" was developed for regulation of the quality parameters of broccoli powders intended for use in the food industry.

  5. 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.

  6. Complex Regulatory Networks Governing Production of the Glycopeptide A40926

    Directory of Open Access Journals (Sweden)

    Rosa Alduina

    2018-04-01

    Full Text Available Glycopeptides (GPAs are an important class of antibiotics, with vancomycin and teicoplanin being used in the last 40 years as drugs of last resort to treat infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. A few new GPAs have since reached the market. One of them is dalbavancin, a derivative of A40926 produced by the actinomycete Nonomuraea sp. ATCC 39727, recently classified as N. gerenzanensis. This review summarizes what we currently know on the multilevel regulatory processes governing production of the glycopeptide A40926 and the different approaches used to increase antibiotic yields. Some nutrients, e.g., valine, l-glutamine and maltodextrin, and some endogenous proteins, e.g., Dbv3, Dbv4 and RpoBR, have a positive role on A40926 biosynthesis, while other factors, e.g., phosphate, ammonium and Dbv23, have a negative effect. Overall, the results available so far point to a complex regulatory network controlling A40926 in the native producing strain.

  7. Complex Regulatory Networks Governing Production of the Glycopeptide A40926.

    Science.gov (United States)

    Alduina, Rosa; Sosio, Margherita; Donadio, Stefano

    2018-04-05

    Glycopeptides (GPAs) are an important class of antibiotics, with vancomycin and teicoplanin being used in the last 40 years as drugs of last resort to treat infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus . A few new GPAs have since reached the market. One of them is dalbavancin, a derivative of A40926 produced by the actinomycete Nonomuraea sp. ATCC 39727, recently classified as N. gerenzanensis . This review summarizes what we currently know on the multilevel regulatory processes governing production of the glycopeptide A40926 and the different approaches used to increase antibiotic yields. Some nutrients, e.g., valine, l-glutamine and maltodextrin, and some endogenous proteins, e.g., Dbv3, Dbv4 and RpoB R , have a positive role on A40926 biosynthesis, while other factors, e.g., phosphate, ammonium and Dbv23, have a negative effect. Overall, the results available so far point to a complex regulatory network controlling A40926 in the native producing strain.

  8. A critical assessment of regulatory triggers for products of biotechnology: Product vs. process

    Science.gov (United States)

    McHughen, Alan

    2016-01-01

    ABSTRACT Regulatory policies governing the safety of genetic engineering (rDNA) and the resulting products (GMOs) have been contentious and divisive, especially in agricultural applications of the technologies. These tensions led to vastly different approaches to safety regulation in different jurisdictions, even though the intent of regulations—to assure public and environmental safety—are common worldwide, and even though the international scientific communities agree on the basic principles of risk assessment and risk management. So great are the political divisions that jurisdictions cannot even agree on the appropriate triggers for regulatory capture, whether product or process. This paper reviews the historical policy and scientific implications of agricultural biotechnology regulatory approaches taken by the European Union, USA and Canada, using their respective statutes and regulations, and then critically assesses the scientific underpinnings of each. PMID:27813691

  9. NASA's Agency-Wide Strategy for Environmental Regulatory Risk Analysis and Communication

    Science.gov (United States)

    Scroggins, Sharon; Duda, Kristen

    2008-01-01

    This viewgraph presentation gives an overview of NASA's risk analysis communication programs associated with changing environmental policies. The topics include: 1) NASA Program Transition; 2) Principal Center for Regulatory Risk Analysis and Communication (RRAC PC); and 3) Regulatory Tracking and Communication Process.

  10. 77 FR 12896 - Self-Regulatory Organizations; Pacific Clearing Corporation; Order Cancelling Clearing Agency...

    Science.gov (United States)

    2012-03-02

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66459; File No. 600-11] Self-Regulatory..., 2006), 72 FR 814 (Jan. 8, 2007). Section 19(a)(3) of the Act \\14\\ provides that in the event any self-regulatory organization is no longer in existence or has ceased to do business in the capacity specified in...

  11. Consumer agency in cannabis supply - Exploring auto-regulatory documents of the cannabis social clubs in Spain.

    Science.gov (United States)

    Belackova, Vendula; Wilkins, Chris

    2018-04-01

    There is growing experience with the not-for-profit, consumer-driven cannabis social club (CSC) model that builds on self-supply, self-organization and harm-reduction; these are principles upon which people who use drugs (PWUD) have been engaging for decades. Recent legalization of cannabis in a number of jurisdictions and the related challenges in regulating production, sale, taxation and health-related matters have raised interest in non-commercial models of cannabis supply. The "codes of conduct" (CsoC) of CSC federations in Spain might reveal whether a consumer-based model could overcome these challenges. To examine the content of the CSC auto-regulatory documents, an online search using key terms to identify the CsoC was conducted. Six documents were found; analysis of the main thematic categories and overarching themes was conducted. It was discussed how these corresponded to the areas of cannabis policy regulation and what the main limitations of the CSC model were. The CsoC detailed the rules for CSC administration, not-for-profit aims, "invitation only" and other conditions of membership, collective cultivation and security as well as for operation of the consumption venue and health-related initiatives. The themes in the CsoC overlapped with cannabis regulatory areas as outlined internationally. Concern over cannabis prices and potency was missing in the CsoC. The potential strengths of the CSC model might include safe environment for peer-delivered harm reduction practice, preventing illicit transactions, quality control, shifting economic surplus to the consumers and increased consumer responsibility. The limitations of the CSC model include high threshold, disguised motives, tax revenue and the risk of both under- and over-regulation. CSCs represent an opportunity to enhance consumer agency and responsibility. The right "to be self-supplied" with psychoactive substances can be granted to consumer associations - but authorities need to provide a

  12. 78 FR 28244 - Agency Information Collection Activities; Proposed Collection; Comment Request

    Science.gov (United States)

    2013-05-14

    ... Licensing of Production and Utilization Facilities,'' specifies technical information and data to be... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2013-0085] Agency Information Collection Activities; Proposed Collection; Comment Request AGENCY: Nuclear Regulatory Commission. ACTION: Notice of pending NRC...

  13. 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

  14. Gasoline toxicology: overview of regulatory and product stewardship programs.

    Science.gov (United States)

    Swick, Derek; Jaques, Andrew; Walker, J C; Estreicher, Herb

    2014-11-01

    Significant efforts have been made to characterize the toxicological properties of gasoline. There have been both mandatory and voluntary toxicology testing programs to generate hazard characterization data for gasoline, the refinery process streams used to blend gasoline, and individual chemical constituents found in gasoline. The Clean Air Act (CAA) (Clean Air Act, 2012: § 7401, et seq.) is the primary tool for the U.S. Environmental Protection Agency (EPA) to regulate gasoline and this supplement presents the results of the Section 211(b) Alternative Tier 2 studies required for CAA Fuel and Fuel Additive registration. Gasoline blending streams have also been evaluated by EPA under the voluntary High Production Volume (HPV) Challenge Program through which the petroleum industry provide data on over 80 refinery streams used in gasoline. Product stewardship efforts by companies and associations such as the American Petroleum Institute (API), Conservation of Clean Air and Water Europe (CONCAWE), and the Petroleum Product Stewardship Council (PPSC) have contributed a significant amount of hazard characterization data on gasoline and related substances. The hazard of gasoline and anticipated exposure to gasoline vapor has been well characterized for risk assessment purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Enhancing Tissue Engineering and Regenerative Medicine Product Commercialization: The Role of Science in Regulatory Decision-Making for the TE/RM Product Development.

    Science.gov (United States)

    Bertram, Timothy A; Johnson, Peter C; Tawil, Bill J; Van Dyke, Mark; Hellman, Kiki B

    2015-10-01

    TERMIS-AM Industry Committee (TERMIS-AM/IC), in collaboration with the TERMIS-Europe (EU)/IC, conducted a symposium involving the European Medicines Agency and the U.S. Food and Drug Administration (FDA) toward building an understanding of the rational basis for regulatory decision-making and providing a framework for decisions made during the evaluation of safety and efficacy of TE/RM technologies. This symposium was held in August 2012 during the TERMIS-WC in Vienna, Austria. Emerging from this international initiative by the European Union and the United States, representatives from the respective agencies demonstrated that there are ongoing interagency efforts for developing common national practices toward harmonization of regulatory requirements for the TE/RM products. To extend a broad-based understanding of the role of science in regulatory decision-making, TERMIS-AM/IC, in cooperation with the FDA, organized a symposium at the 2014 TERMIS-AM Annual Meeting, which was held in Washington, DC. This event provided insights from leaders in the FDA and TERMIS on the current status of regulatory approaches for the approved TE/RM products, the use of science in making regulatory decisions, and TE/RM technologies that are in the development pipeline to address unmet medical needs. A far-ranging discussion with FDA representatives, industrialists, physicians, regenerative medicine biologists, and tissue engineers considered the gaps in today's scientific and regulatory understanding of TE/RM technologies. The identified gaps represent significant opportunities to advance TE/RM technologies toward commercialization.

  16. Cell therapy medicinal product regulatory framework in Europe and its application for MSC-based therapy development

    Science.gov (United States)

    Ancans, Janis

    2012-01-01

    Advanced therapy medicinal products (ATMPs), including cell therapy products, form a new class of medicines in the European Union. Since the ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT) has been established at the European Medicines Agency (EMA) for centralized classification, certification and evaluation procedures, and other ATMP-related tasks. Guidance documents, initiatives, and interaction platforms are available to make the new framework more accessible for small- and medium-sized enterprises, academia, hospitals, and foundations. Good understanding of the centralized and national components of the regulatory system is required to plan product development. It is in the best interests of the cell therapy developers to utilize the resources provided starting with the pre-clinical stage. Whilst there have been no mesenchymal stem cell (MSC)-based medicine authorizations in the EU, three MSC products have received marketing approval in other regions since 2011. The information provided on the regulatory requirements, procedures, and initiatives is aimed at facilitating MSC-based medicinal product development and authorization in the EU. PMID:22912639

  17. Recombinant biologic products versus nutraceuticals from plants - a regulatory choice?

    Science.gov (United States)

    Drake, Pascal M W; Szeto, Tim H; Paul, Mathew J; Teh, Audrey Y-H; Ma, Julian K-C

    2017-01-01

    Biotechnology has transformed the potential for plants to be a manufacturing source of pharmaceutical compounds. Now, with transgenic and transient expression techniques, virtually any biologic, including vaccines and therapeutics, could be manufactured in plants. However, uncertainty over the regulatory path for such new pharmaceuticals has been a deterrent. Consideration has been given to using alternative regulatory paths, including those for nutraceuticals or cosmetic agents. This review will consider these possibilities, and discuss the difficulties in establishing regulatory guidelines for new pharmaceutical manufacturing technologies. © 2016 The British Pharmacological Society.

  18. 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.

  19. As agências reguladoras e o modelo constitucional brasileiro / Regulatory Agencies and the Constitutional Brazilian System

    Directory of Open Access Journals (Sweden)

    Ana Carolina Borges de Oliveira

    2018-05-01

    Full Text Available Purpose – This article tackles the role of the regulatory agencies and, therefore, verifies the separation of powers model adopted by the Brazilian Constitution, focused on how the constitutional Brazilian system adopted the liberal principle of the separation of powers. Methodology/approach/design – This research analyzes Montesquieu’s theory of separation of powers and its influence on the constitutional Brazilian system. It studies the model proposed by Jürgen Habermas, who proposes a discursive theory of law. Finally, it examines the regulatory phenomenon in Brazil, as well as the structure and the roles played by regulatory agencies in acts. Findings – It is concluded that the role of regulatory agencies in the constitutional Brazilian system can be framed as the new actor in the policy formation process that culminates in decisions about laws and policies. Resumo Propósito – O presente estudo pretende investigar o papel normativo das agências reguladoras e, por conseguinte, verificar se o modelo de separação de poderes adotado pela atual Constituição Federal estaria superado, ou seja, busca-se analisar se há uma incompatibilidade entre o modelo constitucional brasileiro e a atividade normativa desenvolvida pelas agências reguladoras no Brasil. Metodologia/abordagem/design – A presente pesquisa terá como pressupostos teóricos a teoria da separação de poderes desenvolvida por Montesquieu e sua influência nas ordens política e jurídica brasileiras. Adotará, também, como base teórica, o modelo proposto por Jürgen Habermas. Por fim, analisará o fenômeno regulatório no Brasil, bem como a estrutura e os papéis desempenhados pelas agências reguladoras no atual sistema; a fim de verificar se é possível defender que a teoria da separação dos poderes proposta pela Constituição Federal de 1988 está superada Resultados – Conclui-se que o papel desempenhado pelas agências reguladoras no contexto jur

  20. The accountability of the brazilian regulatory agencies: the experience of the National Petroleum Agency; O controle externo das agencias reguladoras: o caso da Agencia Nacional do Petroleo

    Energy Technology Data Exchange (ETDEWEB)

    Pinto Junior, Helder Queiroz; Borges, Heloisa Lopes [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Economia. Grupo de Economia da Energia

    2004-07-01

    During the reform process for which passed the Brazilian Oil and Gas Industry, the academic debate was centered mostly in the sectorial restructuring process, in the contract designs and regulatory environment for the industries in change, particularly the desired attributes of its institutions. The debate tends, in the present, to converge towards the existence of different possible combinations between market structures and institutional structures (the regulators among them) that would lead to a desirable result. Thus, the various characteristics and configurations, originally appointed as necessary conditions for the success of any reform, are not dealt with such great deference anymore. The hypothesis that the existence of a independent regulator is a determinant choice for the success of structural and institutional reforms was relaxed as general rule, but there are still strong economic reasons to justify the option, adopted in Brazil. The creation of the Oil National Agency (ANP), the Brazilian regulator for the Oil and Gas Industry is a recent phenomenon. And few studies specifically approach the issue of its accountability, institutional role that in Brazil is delegated mostly, but not exclusively, to the National Court of Accounts (Tribunal de Contas da Uniao). Therefore, the objective of this work will be to discuss the different possibilities of accountability over the ANP, evaluating the paper and the functions of the TCU and the forms of external control on the Agency, pointing out the possibilities, the impediments and the challenges, as well as the economic consequences to the Natural Gas Industry of the current configuration. (author)

  1. Regulatory/Scientific Supports for Micro-, Small-, and Medium-Sized Enterprises (SMEs) With Medicinal Products Provided by the PMDA and EMA.

    Science.gov (United States)

    Kondo, Hideyuki; Shibatsuji, Masayoshi; Yasuda, Naoyuki

    2018-01-01

    Micro-, small-, and medium-sized enterprises (SMEs) have been considered as key players who can bring innovative medicinal products and/or technologies into the field. However, they may need much regulatory/scientific supports to provide their products, technologies, or services to the market in a timely way. Both the Pharmaceuticals and Medical Devices Agency (PMDA) and the European Medicines Agency (EMA), regulatory authorities for medicinal products in Japan and the EU, respectively, have prepared supportive measures for SMEs from the early phase of product/technology development to the postmarketing phase. With respect to supports for SMEs, both agencies have provided similar SME-specific supportive activities, including routine administrative assistance, consultations about product development strategy from an early phase, as well as specific regulatory/scientific issues and fee incentives. In addition, there is a system to register SME status in the EU, which can be a tool for regulators to know how much potential SME-driven activities have and with whom they should communicate to provide necessary supports. Furthermore, as new technologies and novel products from SMEs are not limited to the region where they are developed, close communication about these topics between the PMDA and the EMA will contribute to advancing patients' access to necessary medicinal products.

  2. Common market but divergent regulatory practices: exploring European regulation and the effect on regulatory uncertainty in the marketing authorization of medical products

    NARCIS (Netherlands)

    Chowdhury, Nupur

    2013-01-01

    The medical product sector is characterised by a regulatory patchwork of European and national laws and guidelines operating concurrently with each other. Each of these sectors are characterised by different levels of regulatory uncertainty that may undermine the effectiveness of the regulatory

  3. Agency rivalry in a shared regulatory space and its impact on social welfare

    DEFF Research Database (Denmark)

    Gedefaw Abate, Tenaw; Nielsen, Rasmus; Nielsen, Max

    2018-01-01

    for the best interest of the people, they can have their own rational agendas; such as career advancement, self-aggrandizement and loyalty for a particular political ideology. We show that when officials are non-benevolent and agencies have unequal relative decision-making power, it is likely that a more...

  4. Quality Issues Identified During the Evaluation of Biosimilars by the European Medicines Agency's Committee for Medicinal Products for Human Use.

    Science.gov (United States)

    Cilia, Mark; Ruiz, Sol; Richardson, Peter; Salmonson, Tomas; Serracino-Inglott, Anthony; Wirth, Francesca; Borg, John Joseph

    2018-02-01

    The aim of this study was to identify trends in deficiencies raised during the EU evaluation of the quality part of dossiers for marketing authorisation applications of biosimilar medicinal products. All adopted day 120 list of questions on the quality module of 22 marketing authorisation applications for biosimilars submitted to the European Medicines Agency and concluded by the end of October 2015 was analysed. Frequencies of common deficiencies identified were calculated and summarised descriptions included. Frequencies and trends on quality deficiencies were recorded and presented for 22 biosimilar applications. Thirty-two 'major objections' for 9 products were identified from 14 marketing authorisation applications with 15 raised for drug substance and 17 for drug product. In addition, 547 'other concerns' for drug substance and 495 for drug product were also adopted. The frequencies and trends of the identified deficiencies together with their impact were discussed from a regulatory perspective and how these impact key manufacturing processes and key materials used in the production of biosimilars. This study provides an insight to the regulatory challenges prospective companies need to consider when developing biosimilars; it also helps elucidate common pitfalls in the development and production of biosimilars and in the submission of dossiers for their marketing authorisations. The results are expected to be of interest to pharmaceutical companies but also to regulators to obtain consistent information on medicinal products based on transparent rules safeguarding the necessary pharmaceutical quality of medicinal products.

  5. Mapping knowledge investments in the aftermath of Hurricane Katrina: a new approach for assessing regulatory agency responses to environmental disaster

    International Nuclear Information System (INIS)

    Frickel, Scott; Campanella, Richard; Vincent, M. Bess

    2009-01-01

    In the aftermath of large-scale disasters, the public's dependency on federal and state agencies for information about public safety and environmental risk is acute. While formal rules and procedures are in place to guide policy decisions in environmental risk assessment of spatially concentrated hazards such as regulated waste sites or vacant city lots, standard procedures for risk assessment seem potentially less well-suited for urban-scale disaster zones where environmental hazards may be widely dispersed and widely varying. In this paper we offer a new approach for the social assessment of regulatory science in response to large-scale disaster, illustrating our methodology through a socio-spatial analysis of the U.S. Environmental Protection Agency's (EPA) hazard assessment in New Orleans, Louisiana, following Hurricane Katrina in 2005. We find that the agency's commitment of epistemic resources or 'knowledge investments' varied considerably across the flood-impacted portion of the city, concentrating in poorer and disproportionately African American neighborhoods previously known to be heavily contaminated. We address some of the study's social and policy implications, noting the multidimensionality and interactive nature of knowledge investments and the prospects for deepening and extending this approach through comparative research

  6. Regulatory reforms and productivity: An empirical analysis of the Japanese electricity industry

    International Nuclear Information System (INIS)

    Nakano, Makiko; Managi, Shunsuke

    2008-01-01

    The Japanese electricity industry has experienced regulatory reforms since the mid-1990s. This article measures productivity in Japan's steam power-generation sector and examines the effect of reforms on the productivity of this industry over the period 1978-2003. We estimate the Luenberger productivity indicator, which is a generalization of the commonly used Malmquist productivity index, using a data envelopment analysis approach. Factors associated with productivity change are investigated through dynamic generalized method of moments (GMM) estimation of panel data. Our empirical analysis shows that the regulatory reforms have contributed to productivity growth in the steam power-generation sector in Japan

  7. The Belgian regulatory framework for NORM industries : test-case of a phosphate production plant

    International Nuclear Information System (INIS)

    Pepin, Stephane; Dehandschutter, Boris; Poffijn, Andre; Michel Sonck

    2008-01-01

    According to the Belgian radiation protection regulatory framework, some categories of NORM industries must register to the competent Belgian radiation protection authority (FANC, Federal Agency for Nuclear Control). The facilities must provide a set of information which allows the authority to assess the radiological impact of the industrial activity on the workers, the population and the environment. If the dose exceeds or is likely to exceed 1 mSv/y, corrective measures have to be implemented. FANC has issued a methodology in order to define more precisely the data needed to evaluate the radiological impact. The methodology lists also the exposure pathways which have to be taken into account and the relevant parameters for the evaluation of the doses. The case of a phosphate production plant is discussed in more details: although the exposure of the workers in the production process as such is rather limited, the specific activity of some residues (calcium fluoride sludge) reaches around 10 kBq/kg of Ra-226. This sludge is disposed off in a specific landfill for which a program of radiological monitoring has been implemented. It includes periodic measurements of dose rate and radon concentration on the landfill. (author)

  8. The Regulatory Consumer: Prosumer-Driven Local Energy Production Initiatives

    NARCIS (Netherlands)

    Butenko, A.; Cseres, K.

    2015-01-01

    This paper analyzes the (pro)active role consumers could (and are encouraged by the respective policy to) assume in markets that emerged due to European market liberalization and technological changes. These changes expanded consumer markets and changed regulatory architectures accordingly.

  9. 41 CFR 101-26.602 - Fuels and packaged petroleum products obtained from or through the Defense Logistics Agency.

    Science.gov (United States)

    2010-07-01

    ... petroleum products obtained from or through the Defense Logistics Agency. 101-26.602 Section 101-26.602... Logistics Agency. (a) Agencies shall be governed by the provisions of this § 101-26.602 in satisfying... petroleum products from or through the Defense Logistics Agency. (b) The Defense Logistics Agency has been...

  10. [Neuronal and hormonal regulatory mechanisms of tears production and secretion].

    Science.gov (United States)

    Mrugacz, Małgorzata; Zywalewska, Nella; Bakunowicz-Lazarczyk, Alina

    2005-01-01

    The ocular surface, tear film, lacrimal glands act as a functional unit to preserve the quality of the refractive surface of the eye, and to resist injury and protect the eye against bodily and environmental conditions. Homeostasis of this functional unit involves neuronal and hormonal regulatory mechanisms. The eye appears to be a target organ for sex hormones particulary the androgen, as they modulate the immune system and trophic functions of the lacrimal and Meibomian glands.

  11. An abuse of risk assessment: how regulatory agencies improperly adopted LNT for cancer risk assessment.

    Science.gov (United States)

    Calabrese, Edward J

    2015-04-01

    The Genetics Panel of the National Academy of Sciences' Committee on Biological Effects of Atomic Radiation (BEAR) recommended the adoption of the linear dose-response model in 1956, abandoning the threshold dose-response for genetic risk assessments. This recommendation was quickly generalized to include somatic cells for cancer risk assessment and later was instrumental in the adoption of linearity for carcinogen risk assessment by the Environmental Protection Agency. The Genetics Panel failed to provide any scientific assessment to support this recommendation and refused to do so when later challenged by other leading scientists. Thus, the linearity model used in cancer risk assessment was based on ideology rather than science and originated with the recommendation of the NAS BEAR Committee Genetics Panel. Historical documentation in support of these conclusions is provided in the transcripts of the Panel meetings and in previously unexamined correspondence among Panel members.

  12. 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

  13. Health Physics Society Comments to U.S. Environmental Protection Agency Regulatory Reform Task Force.

    Science.gov (United States)

    Ring, Joseph; Tupin, Edward; Elder, Deirdre; Hiatt, Jerry; Sheetz, Michael; Kirner, Nancy; Little, Craig

    2018-05-01

    The Health Physics Society (HPS) provided comment to the U.S. Environmental Protection Agency (EPA) on options to consider when developing an action plan for President Trump's Executive Order to evaluate regulations for repeal, replacement, or modification. The HPS recommended that the EPA reconsider their adherence to the linear no-threshold (LNT) model for radiation risk calculations and improve several documents by better addressing uncertainties in low-dose, low dose-rate (LDDR) radiation exposure environments. The authors point out that use of the LNT model near background levels cannot provide reliable risk projections, use of the LNT model and collective-dose calculations in some EPA documents is inconsistent with the recommendations of international organizations, and some EPA documents have not been exposed to the public comment rule-making process. To assist in establishing a better scientific basis for the risks of low dose rate and low dose radiation exposure, the EPA should continue to support the "Million Worker Study," led by the National Council on Radiation Protection and Measurement.

  14. Regulatory Considerations for Gene Therapy Products in the US, EU, and Japan.

    Science.gov (United States)

    Halioua-Haubold, Celine-Lea; Peyer, James G; Smith, James A; Arshad, Zeeshaan; Scholz, Matthew; Brindley, David A; MacLaren, Robert E

    2017-12-01

    Developers of gene therapy products (GTPs) must adhere to additional regulation beyond that of traditional small-molecule therapeutics, due to the unique mechanism-of-action of GTPs and the subsequent novel risks arisen. We have provided herein a summary of the regulatory structure under which GTPs fall in the United States, the European Union, and Japan, and a comprehensive overview of the regulatory guidance applicable to the developer of GTP. Understanding the regulatory requirements for seeking GTP market approval in these major jurisdictions is crucial for an effective and expedient path to market. The novel challenges facing GTP developers is highlighted by a case study of alipogene tiparvovec (Glybera).

  15. Global regulatory framework for production and marketing of crops biofortified with vitamins and minerals.

    Science.gov (United States)

    Mejia, Luis A; Dary, Omar; Boukerdenna, Hala

    2017-02-01

    Biofortification of crops is being introduced in several countries as a strategy to reduce micronutrient deficiencies. Biofortified products, with increased contents of micronutrients, are currently produced by conventional plant breeding, genetic modification, or nutrient-enhanced fertilization. Corn, rice, wheat, beans, pearl millet, sweet potato, and cassava have been biofortified with increased contents of provitamin A carotenoids, iron, or zinc. However, regulatory considerations are rare or nonexistent. The objective of this paper is to review the regulatory framework for production and marketing of biofortified crops in countries that have adopted this strategy. The information was identified using Internet search engines and websites of health and nutrition organizations and nongovernmental organizations and by consulting scientists and government authorities. Thus far, biofortified products introduced in Latin America, Africa, and Asia have been produced only by conventional breeding. Cultivars using other techniques are still under testing. The production and marketing of these products have been conducted without regulatory framework and under limited government control or regulatory guidance. Nevertheless, some countries have integrated biofortified crops into their nutrition agendas. Although improvements by conventional breeding have not been subject to regulations, when biofortification becomes expanded by including other techniques, an appropriate regulatory framework will be necessary. © 2016 New York Academy of Sciences.

  16. Engineered Nanoscale Materials and Derivative Products: Regulatory Challenges

    National Research Council Canada - National Science Library

    Schierow, Linda-Jo

    2008-01-01

    .... government has invested billions of dollars to ensure that American industry remains a global leader in the field, because the products of nanotechnology are seen to have great economic potential...

  17. Options for electricity production, the actual opportunities and regulatory framework

    International Nuclear Information System (INIS)

    Raphals, P.

    2006-01-01

    Thermal power and nuclear power represent the traditional methods of generating electricity. This paper presented opportunities for alternative centralized power production methods that include wind energy, biomass and solar energy. It also discussed decentralized alternatives for power generation, such as geothermal energy and cogeneration, including microturbines. The primary focus was on aspects of competitive market design for residential and small commercial applications as well as commercial and industrial applications. Law 116 of Quebec's Energy Board was reviewed in terms of energy policy and utility regulation. In particular, the framework agreement between Hydro-Quebec Production (HQP) and Hydro-Quebec Distribution (HQD) was discussed with reference to balancing electricity produced from renewable energy sources and energy security. The presentation also addressed issues regarding the role of competition, regulation and environmental implications of electricity trade. refs., tabs., figs

  18. Raw materials in the manufacture of biotechnology products: regulatory considerations.

    Science.gov (United States)

    Cordoba-Rodriguez, Ruth

    2010-01-01

    The Food and Drug Administration's Pharmaceutical cGMPs for the 21st Century initiative emphasizes science and risk-based approaches in the manufacture of drugs. These approaches are reflected in the International Conference on Harmonization (ICH) guidances ICH Q8, Q9, and Q10 and encourage a comprehensive assessment of the manufacture of a biologic, including all aspects of manufacture that have the potential to affect the finished drug product. Appropriate assessment and management of raw materials are an important part of this initiative. Ideally, a raw materials program should strive to assess and minimize the risk to product quality. With this in mind, risk-assessment concepts and control strategies will be discussed and illustrated by examples, with an emphasis on the impact of raw materials on cell substrates. Finally, the life cycle of the raw material will be considered, including its potential to affect the drug product life cycle. In this framework, the supply chain and the vendor-manufacturer relationship will be explored as important parts of an adequate raw materials control strategy.

  19. Promotion and regional development. Implementation of regional productive development agencies. The case of Maule region, Chile

    Directory of Open Access Journals (Sweden)

    Enrique Yamil Alul González

    2010-12-01

    Full Text Available The Regional Productive Development Agencies implemented in Chile in 2006, were developed as a way to answer the longing desire to territorially decentralize, and that the own Regions be whom define their future. The Agencies have the responsibility to develop innovation and productive development Agendas in participative processes, which means with public, academic and private actors. Also, the Agencies have the mission to implement Competitive Improvement Plans-PMC (clusters in prioritized economic sectors by the own region. These PMC are leaded by private actors in each sector.

  20. Bringing a probiotic-containing functional food to the market: microbiological, product, regulatory and labeling issues.

    Science.gov (United States)

    Sanders, M E; Huis in't Veld, J

    1999-01-01

    Properly formulated probiotic-containing foods offer consumers a low risk, low cost dietary component that has the potential to promote health in a variety of ways. Several such products are available commercially, although markets in Japan and Europe are more developed than in the USA. Once healthful attributes of a probiotic product have been identified, there remain microbiological, product, regulatory and labeling issues to be addressed prior to marketing. Microbiological and product issues include safety, effective scale-up for manufacturing, definition of probiotic activity, probiotic stability in the product over the course of product manufacture, shelf-life and consumption, definition of effective dose and target population(s), and development of quality assurance approaches. Examples of probiotic-containing foods are given. Regulatory and labeling issues are complicated because they differ for each country, but are likewise critical because they provide the means for communication of the product benefits to the consumer. The regulatory climate worldwide appears to be one of caution about overstating the benefits of such products but at the same time not preventing corporate commitment to marketing.

  1. [Regulatory requirements regarding cell-based medicinal products for human and veterinary use - a comparison].

    Science.gov (United States)

    Kuhlmann-Gottke, Johanna; Duchow, Karin

    2015-11-01

    At present, there is no separate regulatory framework for cell-based medicinal products (CBMP) for veterinary use at the European or German level. Current European and national regulations exclusively apply to the corresponding medicinal products for human use. An increasing number of requests for the regulatory classification of CBMP for veterinary use, such as allogeneic stem cell preparations and dendritic cell-based autologous tumour vaccines, and a rise in scientific advice for companies developing these products, illustrate the need for adequate legislation. Currently, advice is given and decisions are made on a case-by-case basis regarding the regulatory classification and authorisation requirements.Since some of the CBMP - in particular in the area of stem-cell products - are developed in parallel for human and veterinary use, there is an urgent need to create specific legal definitions, regulations, and guidelines for these complex innovative products in the veterinary sector as well. Otherwise, there is a risk that that the current legal grey area regarding veterinary medicinal products will impede therapeutic innovations in the long run. A harmonised EU-wide approach is desirable. Currently the European legislation on veterinary medicinal products is under revision. In this context, veterinary therapeutics based on allogeneic cells and tissues will be defined and regulated. Certainly, the legal framework does not have to be as comprehensive as for human CBMP; a leaner solution is conceivable, similar to the special provisions for advanced-therapy medicinal products laid down in the German Medicines Act.

  2. Current products and future plan of regulatory research for risk-informed regulation in Korea

    International Nuclear Information System (INIS)

    Sung, Key Yong; Lee, Chang Ju; Kim, Woong Sik; Kim, Hho Jung

    2003-01-01

    The first phase of a regulatory research project for risk-informed regulation (RIR) and applications (RIA) was finished in March of 2002. Various results that could be useful for preparing Korean RIR system have been developed. One of the remarkable outputs is development of reactor safety goals and acceptance criteria for RIR and RIA in Korea. The Safety Goal has a 4-tier hierarchical structure and each tier has specified goals classified for their usage. Regulatory review guides for probabilistic safety assessment (PSA) including level-1, level-2 and low power and shutdown PSA have been updated by reflecting new information obtained from not only the overseas documents but also experience and insights from regulatory review in Korea. In addition, draft regulatory guides for risk-informed in-service inspection, in-service testing, importance ranking of motor-operated valves, and AOT/STI change of Technical Specifications have been developed for preparing ongoing and future licensing work. Risk-based inspection guides with inspection items selected from a viewpoint of risk importance have been suggested for Korean standard NPPs as well. In the second phase of a research project (April of 2002 to March of 2005), two regulatory research projects on RIR were initiated. One is a study on institutionalization of risk-informed and performance-based regulation. Main topics of this project are evaluation of benefit and characteristics of RIR, development of optimized Korean RIR model, impact analysis for the change of current regulation framework, and suggestion of RIR-related laws and rules. The other is focusing on the development in the areas of a regulatory audit PSA model and regulatory guides for risk monitoring, and application techniques of risk information to the significance determination of plant performance indicators and inspection findings. It is expected that a concrete scheme and detailed regulatory techniques for embodiment of RIR system in Korea will be

  3. Play, Create, Share? Console Gaming, Player Production and Agency

    Directory of Open Access Journals (Sweden)

    Olli Sotamaa

    2010-07-01

    Full Text Available Digital games have been frequently used to illustrate the new organisational frameworks that are based on persuading users to carry out tasks and assignments not traditionally associated with them. However coined, ‘user-innovation’ (von Hippel, 2005, ‘crowdsourcing’ (Howe, 2008 or ‘pro-am revolution’ (Leadbeater and Miller, 2004, contemporary examples of this phenomena always include digital games. A closer look at the recent open innovation manifestos reveals that the oft-cited examples come almost entirely from PC games while console games remain mostly non-existent in these texts. It is clear that PC and console games differ both in use and in the cultures they create (Taylor, 2007. Equally, the technological and economic backgrounds of the market sectors have their differences (Kerr, 2006.The concept of LittleBigPlanet, a console game inherently dependent on player production, challenges the neat binary of some much cited arguments about tethered appliances. The first set of research questions rises from this observation. What are the technical and economic constraints and affordances the console as a platform uses to position the productive activities of players? How do these differ from the forms of player production typical of PC gaming (see Sotamaa, 2007a; and Sotamaa, 2007b?

  4. Regulatory fit effects for injunctive versus descriptive social norms: Evidence from the promotion of sustainable products

    NARCIS (Netherlands)

    Melnyk, V.; Herpen, van E.; Fischer, A.R.H.; Trijp, van J.C.M.

    2013-01-01

    Consumers face marketing messages using social norms in many situations where different goals are dominant. This research examines moderating effects of regulatory focus for descriptive and injunctive norms in the promotion of sustainable products. More specifically, it shows that descriptive norms

  5. Organic Coasts? Regulatory Challenges of Certifying Integrated Shrimp-Mangrove Production Systems in Vietnam

    Science.gov (United States)

    Ha, Tran Thi Thu; Bush, Simon R.; Mol, Arthur P. J.; van Dijk, Han

    2012-01-01

    The Vietnamese government aims to expand the scale of Naturland certified organic production in integrated shrimp-mangrove farming systems across the coast of Ca Mau province by 2015. In doing so the division between public and private regulation has become blurred. We analyze the government's goal by examining the regulatory challenges of using…

  6. 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.

  7. 78 FR 35279 - Agency Information Collection Activities; Proposed Collection; Comment Request; Electronic Products

    Science.gov (United States)

    2013-06-12

    ... proposed extension of an existing collection of information, and to allow 60 days for public comment in...)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 60-day notice in... Products'' FDA Form 3646 ``Mercury Vapor Lamp Products Radiation Safety Report'' FDA Form 3647 ``Guide for...

  8. Interchangeability of biosimilar and biological reference product: updated regulatory positions and pre- and post-marketing evidence.

    Science.gov (United States)

    Trifirò, Gianluca; Marcianò, Ilaria; Ingrasciotta, Ylenia

    2018-03-01

    Since 2006, biosimilars have been available in several countries worldwide, thus allowing for potential savings in pharmaceutical expenditure. However, there have been numerous debates about the interchangeability of biosimilars and reference products based on concerns of immunogenicity by switching between biological products, which may cause lack of effect and toxicity. Areas covered: The authors provide the reader with an overview of the different positions of regulatory authorities on the interchangeability and automatic substitution of biosimilars and reference products. Presently, the FDA allows automatic substitution without prescriber intervention if the biosimilar is interchangeable with reference products, while the European Medicines Agency delegate to each single EU member state. Expert opinion: Different approaches in defining interchangeability and automatic substitution call for harmonization to increase confidence of healthcare professionals and patients about the clinical impact of switching. Networks of electronic healthcare records and administrative databases, potentially linkable to clinical charts and registries may rapidly assess frequency and benefit-risk profile of different switching patterns in routine care at different levels, thus integrating and strengthening pre-marketing evidence.

  9. 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.

  10. Health claims on food products in Southeast Asia: regulatory frameworks, barriers, and opportunities.

    Science.gov (United States)

    Tan, Karin Y M; van der Beek, Eline M; Chan, M Y; Zhao, Xuejun; Stevenson, Leo

    2015-09-01

    The Association of Southeast Asian Nations aims to act as a single market and allow free movement of goods, services, and manpower. The purpose of this article is to present an overview of the current regulatory framework for health claims in Southeast Asia and to highlight the current barriers and opportunities in the regulatory frameworks in the Association of Southeast Asian Nations. To date, 5 countries in Southeast Asia, i.e., Indonesia, Malaysia, the Philippines, Singapore, and Thailand, have regulations and guidelines to permit the use of health claims on food products. There are inconsistencies in the regulations and the types of evidence required for health claim applications in these countries. A clear understanding of the regulatory frameworks in these countries may help to increase trade in this fast-growing region and to provide direction for the food industry and the regulatory community to develop and market food products with better nutritional quality tailored to the needs of Southeast Asian consumers. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. The role of radiation regulatory agencies of the Republic of the Philippines in the education and training of workers occupationally exposed to radiation

    International Nuclear Information System (INIS)

    Perio Peralta, Agnette de

    2008-01-01

    In the Republic of the Philippines, there are two national radiation regulatory agencies. One is the Philippine Nuclear Research Institute (PNRI) which has the regulatory mandate over radioactive materials. The other one is the Bureau of Health Devices and Technology (BHDT) which has the regulatory mandate over radiation devices. Since a major requirement in regulating use of radiation sources is the appropriate qualification of the workers occupationally exposed to radiation, the paper discusses the strategies and activities of these two agencies to ensure that these workers have the necessary education and training to do their work properly. Some of these are the conduct of training courses in cooperation with the relevant professional societies, conduct of distance aided training in cooperation with the IAEA, initiation and active involvement in the establishment and continued existence of the masteral degree program in medical physics which was established with IAEA technical assistance, assistance to lawmakers in drafting pertinent legislation, and creation of joint technical working groups to ensure harmonization of standards and regulations, among others. The Philippines has adopted a national policy that users of radiation and radioactive materials have the primary responsibility for radiation safety. The PNRI and the BHDT have adopted strategies which have been very useful in the effective implementation of their regulations. (author)

  12. 2014 White Paper on recent issues in bioanalysis: a full immersion in bioanalysis (Part 2 - hybrid LBA/LCMS, ELN & regulatory agencies' input).

    Science.gov (United States)

    Dufield, Dawn; Neubert, Hendrik; Garofolo, Fabio; Kirkovsky, Leo; Stevenson, Lauren; Dumont, Isabelle; Kaur, Surinder; Xu, Keyang; Alley, Stephen C; Szapacs, Matthew; Arnold, Mark; Bansal, Surendra; Haidar, Sam; Welink, Jan; Le Blaye, Olivier; Wakelin-Smith, Jason; Whale, Emma; Ishii-Watabe, Akiko; Bustard, Mark; Katori, Noriko; Amaravadi, Lakshmi; Aubry, Anne-Françoise; Beaver, Chris; Bergeron, Annik; Cai, Xiao-Yan; Cojocaru, Laura; DeSilva, Binodh; Duggan, Jeff; Fluhler, Eric; Gorovits, Boris; Gupta, Swati; Hayes, Roger; Ho, Stacy; Ingelse, Benno; King, Lindsay; Lévesque, Ann; Lowes, Steve; Ma, Mark; Musuku, Adrien; Myler, Heather; Olah, Timothy; Patel, Shefali; Rose, Mark; Schultz, Gary; Smeraglia, John; Swanson, Steven; Torri, Albert; Vazvaei, Faye; Wilson, Amanda; Woolf, Eric; Xue, Li; Yang, Tong-Yuan

    2014-01-01

    The 2014 8th Workshop on Recent Issues in Bioanalysis (8th WRIB), a 5-day full immersion in the evolving field of bioanalysis, took place in Universal City, California, USA. Close to 500 professionals from pharmaceutical and biopharmaceutical companies, contract research organizations and regulatory agencies worldwide convened to share, review, discuss and agree on approaches to address current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches and immunogenicity. From the prolific discussions held during the workshop, specific recommendations are presented in this 2014 White Paper. As with the previous years' editions, this paper acts as a practical tool to help the bioanalytical community continue advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2014 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations for Hybrid LBA/LCMS, Electronic Laboratory Notebook and Regulatory Agencies' Input. Part 1 (Small molecules bioanalysis using LCMS) was published in the Bioanalysis issue 6(22) and Part 3 (Large molecules bioanalysis using LBA and Immunogenicity) will be published in the Bioanalysis issue 6(24).

  13. Manufacturing, regulatory and commercial challenges of biopharmaceuticals production: a Finnish perspective.

    Science.gov (United States)

    Närhi, Marko; Nordström, Katrina

    2005-04-01

    Biopharmaceuticals product development is a broad and multidisciplinary field. Science and technology are combined with new manufacturing, regulatory and commercial challenges. However, although there is ample literature on the molecular biology and biochemistry of products, the implementation of processes from test tube to commercial scale has not received similar attention. Consequently, the present study aims to highlight, from practical point of view, some of the key issues involved with manufacturing technologies of biopharmaceuticals at a commercial scale. Regulatory requirements and investments are also addressed based on the practical experiences of start-up and small companies. Finland is used as a case-example of such companies as this is a EU-member state with strong technological growth and rapidly increasing number of biotech companies.

  14. 78 FR 1624 - Fall 2012 Regulatory Agenda

    Science.gov (United States)

    2013-01-08

    ...), studies or analyses of the possible need for regulatory action, requests for public comment on the need... (NESHAP): Reinforced Plastic Composites Production To comment or learn more about these retrospective.... Agency Contact: Hans Scheifele, Environmental Protection Agency, Office of Chemical Safety and Pollution...

  15. Regulatory Control of Radiation Sources. Safety Guide

    International Nuclear Information System (INIS)

    2009-01-01

    This Safety Guide is intended to assist States in implementing the requirements established in Safety Standards Series No. GS-R-1, Legal and Governmental Infrastructure for Nuclear, Radiation, Radioactive Waste and Transport Safety, for a national regulatory infrastructure to regulate any practice involving radiation sources in medicine, industry, research, agriculture and education. The Safety Guide provides advice on the legislative basis for establishing regulatory bodies, including the effective independence of the regulatory body. It also provides guidance on implementing the functions and activities of regulatory bodies: the development of regulations and guides on radiation safety; implementation of a system for notification and authorization; carrying out regulatory inspections; taking necessary enforcement actions; and investigating accidents and circumstances potentially giving rise to accidents. The various aspects relating to the regulatory control of consumer products are explained, including justification, optimization of exposure, safety assessment and authorization. Guidance is also provided on the organization and staffing of regulatory bodies. Contents: 1. Introduction; 2. Legal framework for a regulatory infrastructure; 3. Principal functions and activities of the regulatory body; 4. Regulatory control of the supply of consumer products; 5. Functions of the regulatory body shared with other governmental agencies; 6. Organization and staffing of the regulatory body; 7. Documentation of the functions and activities of the regulatory body; 8. Support services; 9. Quality management for the regulatory system.

  16. An investment-production-regulatory model for firms in the offshore oil and gas industry

    International Nuclear Information System (INIS)

    Jin Di.

    1991-01-01

    This tripartite study examines the economic consequences of proposed environmental regulations on firms in the OCS oil and gas industry. The background part reviews the major issues associated with OCS oil and gas development and relevant environmental regulatory proposals. In the theoretical part, models are developed using optimal control theory and the theory of nonrenewable resources to analyze the impact of rising compliance cost on firm's behavior in terms of the investment and production rates over time. Finally, in the simulation part, an integrated investment-production-regulatory model is developed to simulate OCS development with and without the proposed environmental regulations. Effects of regulations are measured in terms of an increase in compliance costs and the associated reduction in net profits from oil and gas production. The theoretical results indicate that an increase in compliance costs will alter exploration, development and production rates. The total investments in exploration and development, and oil production will decrease as a result of rising compliance costs for exploration, development and production over the entire planning period

  17. Contaminated Non-Food Products. Regulatory Deficit Regarding Contaminated Non-Food Products

    International Nuclear Information System (INIS)

    2015-11-01

    An INES 7 event in Europe will generate tremendous amounts of class 7 goods. From roofing tile to motor cycle, everything becomes a surface contaminated object and therefore a dangerous good. Along with the classification as a dangerous good goes the classification as waste. Who would buy a commodity that cannot be shipped without special care? Thus, ADR/RID induce a de facto dose limit for commodities, whether intended or not. Within the present ADR/RID this regulatory checkmate can hardly be avoided. National exemptions are impossible and with a view to the European internal market even pointless. Here we present a harmonised description of this particular checkmate. We discuss two specific scenarios and the corresponding regulatory issues

  18. Regulatory requirements for clinical trial and marketing authorisation application for cell-based medicinal products.

    Science.gov (United States)

    Salmikangas, P; Flory, E; Reinhardt, J; Hinz, T; Maciulaitis, R

    2010-01-01

    The new era of regenerative medicine has led to rapid development of new innovative therapies especially for diseases and tissue/organ defects for which traditional therapies and medicinal products have not provided satisfactory outcome. Although the clinical use and developments of cell-based medicinal products (CBMPs) could be witnessed already for a decade, robust scientific and regulatory provisions for these products have only recently been enacted. The new Regulation for Advanced Therapies (EC) 1394/2007 together with the revised Annex I, Part IV of Directive 2001/83/EC provides the new legal framework for CBMPs. The wide variety of cell-based products and the foreseen limitations (small sample sizes, short shelf life) vs. particular risks (microbiological purity, variability, immunogenicity, tumourigenicity) associated with CBMPs have called for a flexible, case-by-case regulatory approach for these products. Consequently, a risk-based approach has been developed to allow definition of the amount of scientific data needed for a Marketing Authorisation Application (MAA) of each CBMP. The article provides further insight into the initial risk evaluation, as well as to the quality, non-clinical, and clinical requirements of CBMPs. Special somatic cell therapies designed for active immunotherapy are also addressed.

  19. The use and interpretation of in vitro data in regulatory toxicology: cosmetics, toiletries and household products.

    Science.gov (United States)

    Indans, Ian

    2002-02-28

    There is currently a drive to eliminate animal testing for cosmetics, toiletries and household products; indeed, the European Union Cosmetics Directive aims to prohibit the use of experimental animals for the testing of finished cosmetic products after 2002. At present, national prohibitions are in place in the UK, Germany, Austria and the Netherlands, for the testing of finished cosmetic products and cosmetic ingredients. In the USA animal testing for certain types of finished products is mandatory. Against this background, the currently available regulatory in vitro tests comprise methods for eye irritation, skin corrosivity, genotoxicity, dermal penetration and photoirritation. The draft updates to the Organisation for Economic Co-operation and Development guidelines for eye and skin irritation advocate the use of in vitro or ex vivo methods prior to the commencement of animal studies. At present, testing for these endpoints cannot be completed in vitro, but potentially corrosive substances and products can be classified without the need for animal studies. Regulatory genotoxicity testing can be completed using only in vitro methods, provided that a clear negative outcome is obtained for each test. Data from dermal penetration studies may be used to refine risk assessments. Current developments in areas such as skin sensitisation and skin irritation promise that in the reasonably near future such information may be generated without the use of animals.

  20. Cross-border temporary agency work : Social sustainability of a business model (too often) based on regulatory arbitrage

    NARCIS (Netherlands)

    Houwerzijl, Mijke; Rombouts, Bas

    Presentation held at the European Regional Congress of the International Society for Labour and Social Security Law (ISLSSL) on Temporary Agency Work in the context of cross-border movement & service provision within the EU.

  1. Ownership options, financing structures, and regulatory considerations affecting independent power production projects

    International Nuclear Information System (INIS)

    Knapp, G.M.

    1990-01-01

    In this paper is a framework for analysis of the legal, financing, and policy differences between independent power production projects (IPPs) and projects with qualifying facility status (QFs) under the Public Utility Regulatory Policies Act (PURPA). At a basic level, there is no fundamental difference in types of ownership and financing structures available to IPPs and QFS. The key consideration, though, is the regulatory and legal implications to project participants. Significant issues arise for equity participants, lenders, developers, and project operators that are considering IPP projects. Of course, many of these same issues apply to certain types of QF projects that are not fully exempt from the Public Utility Holding Company Act (PUHCA) and the Federal Power Act (FPA)

  2. A Study of Efficiency, Effectiveness and Productivity of Filipino Administrative Agencies

    Directory of Open Access Journals (Sweden)

    Santiago Simpas

    1980-01-01

    Full Text Available The public in general would have different ideas regarding "efficiency, effectiveness and productivity" because these concepts have apparently different meanings and purposes. Properly understood and utilized, however, these concepts can be useful tools for improving management in the public service.Employees, supervisors and administrators themselves would have different views of these concepts. Several variables affect the interrelationships between the three factors and it is quite difficult to tell whether or not an agency is really efficient, effective and productive.Intending to operationalize and provide measurements of these concepts in the Philippine setting, this study is a survey on efficiency, effectiveness and productivity of Philippine administrative agencies. Furthermore, insights into the relationships that exist among these three concepts have been obtained and the key variables affecting them identified.More specifically, this study is an examination of the effects of four structural variables – centralization, complexity, formalization and stratification – on efficiency, effectiveness and productivity.During the first phase of the research project, the research team examined organizational records as the basis for the preparation of schedules for study. Pre-tests were done during the first six months of research. Immediately after the formulation of the initial questionnaire, the development of the final questionnaire started. The first set was administered to supervisory personnel of selected units of the four agencies under study - the Department of Health (DOH, the Department of Local Government and Community Development (DLGCD, the Development Bank of the Philippines (DBP and the Government Service Insurance System (GSIS. These agencies were selected on the basis of the primary function of financing and service. The original plan was to have at least six representative agencies of the government for the survey, but due

  3. RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed within a productive fermentation

    Science.gov (United States)

    2013-01-01

    Background The production of enzymes by an industrial strain requires a complex adaption of the bacterial metabolism to the conditions within the fermenter. Regulatory events within the process result in a dynamic change of the transcriptional activity of the genome. This complex network of genes is orchestrated by proteins as well as regulatory RNA elements. Here we present an RNA-Seq based study considering selected phases of an industry-oriented fermentation of Bacillus licheniformis. Results A detailed analysis of 20 strand-specific RNA-Seq datasets revealed a multitude of transcriptionally active genomic regions. 3314 RNA features encoded by such active loci have been identified and sorted into ten functional classes. The identified sequences include the expected RNA features like housekeeping sRNAs, metabolic riboswitches and RNA switches well known from studies on Bacillus subtilis as well as a multitude of completely new candidates for regulatory RNAs. An unexpectedly high number of 855 RNA features are encoded antisense to annotated protein and RNA genes, in addition to 461 independently transcribed small RNAs. These antisense transcripts contain molecules with a remarkable size range variation from 38 to 6348 base pairs in length. The genome of the type strain B. licheniformis DSM13 was completely reannotated using data obtained from RNA-Seq analyses and from public databases. Conclusion The hereby generated data-sets represent a solid amount of knowledge on the dynamic transcriptional activities during the investigated fermentation stages. The identified regulatory elements enable research on the understanding and the optimization of crucial metabolic activities during a productive fermentation of Bacillus licheniformis strains. PMID:24079885

  4. RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed within a productive fermentation.

    Science.gov (United States)

    Wiegand, Sandra; Dietrich, Sascha; Hertel, Robert; Bongaerts, Johannes; Evers, Stefan; Volland, Sonja; Daniel, Rolf; Liesegang, Heiko

    2013-10-01

    The production of enzymes by an industrial strain requires a complex adaption of the bacterial metabolism to the conditions within the fermenter. Regulatory events within the process result in a dynamic change of the transcriptional activity of the genome. This complex network of genes is orchestrated by proteins as well as regulatory RNA elements. Here we present an RNA-Seq based study considering selected phases of an industry-oriented fermentation of Bacillus licheniformis. A detailed analysis of 20 strand-specific RNA-Seq datasets revealed a multitude of transcriptionally active genomic regions. 3314 RNA features encoded by such active loci have been identified and sorted into ten functional classes. The identified sequences include the expected RNA features like housekeeping sRNAs, metabolic riboswitches and RNA switches well known from studies on Bacillus subtilis as well as a multitude of completely new candidates for regulatory RNAs. An unexpectedly high number of 855 RNA features are encoded antisense to annotated protein and RNA genes, in addition to 461 independently transcribed small RNAs. These antisense transcripts contain molecules with a remarkable size range variation from 38 to 6348 base pairs in length. The genome of the type strain B. licheniformis DSM13 was completely reannotated using data obtained from RNA-Seq analyses and from public databases. The hereby generated data-sets represent a solid amount of knowledge on the dynamic transcriptional activities during the investigated fermentation stages. The identified regulatory elements enable research on the understanding and the optimization of crucial metabolic activities during a productive fermentation of Bacillus licheniformis strains.

  5. A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

    Directory of Open Access Journals (Sweden)

    Giannakou C

    2016-06-01

    Full Text Available Christina Giannakou,1,2 Margriet VDZ Park,1 Wim H de Jong,1 Henk van Loveren,1,2 Rob J Vandebriel,1 Robert E Geertsma1 1Centre for Health Protection, National Institute for Public Health and the Environment (RIVM, Bilthoven, 2Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands Abstract: Nanomaterials (NMs are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome

  6. Regulatory assessment of brand changes in the commercial tobacco product market.

    Science.gov (United States)

    Wayne, G Ferris; Connolly, G N

    2009-08-01

    Regulatory oversight of tobacco product design has gained momentum in the US and internationally. Appropriate standards for assessing commercial brands and characterising product features must be considered a priority. An area of potential concern is in-market design changes adopted within a single commercial brand over time. Internal tobacco industry documents were identified and used to assess internal discussion of product guidelines and practices regarding in-market brand changes. Commercial tobacco products undergo a constant process of revision in-market, beginning at the most basic level of physical product characteristics and components, and including every aspect of design. These revisions commonly exceed guidelines for acceptable product variance adopted within the industry. While consumer and market testing is conducted to ensure that products remain acceptable to users, explicit marketing often may not accompany brand changes. In the absence of such marketing, it should not be assumed that a brand remains unchanged. For manufacturers, assessment of competitor brands includes identification and analysis of non-routine changes; that is, those changes likely to significantly alter the character of a given brand. Regulators must adopt a similar practice in determining standards for product evaluation in the face of ongoing commercial product revision.

  7. [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

  8. Delegação e controle político das agências reguladoras no Brasil Delegation and political control of the regulatory agencies in Brazil

    Directory of Open Access Journals (Sweden)

    Fernanda Meirelles

    2006-08-01

    Full Text Available A partir de um esforço de sistematização dos mecanismos de controle político previstos no modelo institucional originalmente concebido para as agências reguladoras, este artigo avalia os mecanismos de controle político presentes no arcabouço institucional das agências reguladoras independentes (ARIs brasileiras e analisa as alterações relacionadas ao controle político introduzidas pelo projeto de lei encaminhado pelo governo ao Congresso em 12 de abril de 2004. Após contextualizar o debate sobre o controle político das ARIs no Brasil, o artigo discute as relações entre delegação e responsabilização. Em seguida, na busca de um parâmetro para avaliar o modelo brasileiro de agências reguladoras (ARs, identifica os instrumentos de controle político utilizados na experiência americana. Finalmente, avalia a realidade institucional atual das ARIs brasileiras e comenta as contribuições do recente projeto de lei em relação ao controle político das agências.This article systematizes the political control mechanisms provided by the institutional model originally conceived for the regulatory agencies in order to assess the political control mechanisms in the institutional framework of the Brazilian independent regulatory agencies (IRAs and analyze the political control changes introduced by the law proposed by the government to Congress in April 12, 2004. After putting into context the debate on political control over the Brazilian IRAs, the article discusses the relationship between delegation and accountability. Then, so as to find a parameter for assessing the Brazilian regulatory agency model, it identifies the political control mechanisms used by the American experience. Finally, it assesses the current institutional situation of the Brazilian IRAs and comments on the contribution of the recent law proposal in relation to agency political control.

  9. 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

  10. Applications of pharmacogenomics in regulatory science: a product life cycle review.

    Science.gov (United States)

    Tan-Koi, W C; Leow, P C; Teo, Y Y

    2018-05-22

    With rapid developments of pharmacogenomics (PGx) and regulatory science, it is important to understand the current PGx integration in product life cycle, impact on clinical practice thus far and opportunities ahead. We conducted a cross-sectional review on PGx-related regulatory documents and implementation guidelines in the United States and Europe. Our review found that although PGx-related guidance in both markets span across the entire product life cycle, the scope of implementation guidelines varies across two continents. Approximately one-third of Food and Drug Administration (FDA)-approved drugs with PGx information in drug labels and half of the European labels posted on PharmGKB website contain recommendations on genetic testing. The drugs affected 19 and 15 World Health Organization Anatomical Therapeutic Chemical drug classes (fourth level) in the United States and Europe, respectively, with protein kinase inhibitors (13 drugs in the United States and 16 drugs in Europe) being most prevalent. Topics of emerging interest were novel technologies, adaptive design in clinical trial and sample collection.

  11. Regulatory challenges for autologous tissue engineered products on their way from bench to bedside in Europe.

    Science.gov (United States)

    Ram-Liebig, Gouya; Bednarz, Juergen; Stuerzebecher, Burkard; Fahlenkamp, Dirk; Barbagli, Guido; Romano, Giuseppe; Balsmeyer, Ulf; Spiegeler, Maria-Elsa; Liebig, Soeren; Knispel, Helmut

    2015-03-01

    Since the late eighties of last century the high potential of tissue engineered products (TEP)s has been shown for the treatment of various diseases and many scientific publications appeared in this field. However, only few products reached the market since. Development of TEPs is a promising but owing to its novelty a very challenging task that requires experts in this still developing field as well as ample financial resources. This paper summarises relevant regulatory challenges during quality, preclinical and clinical development of autologous TEPs in Europe. Selected strategies on how to manage major issues are presented, together with some examples from the development of an autologous TEP for urethroplasty. Considering these aspects may help other investigators with potential strategies during the development of novel TEPs. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements.

    Science.gov (United States)

    Giannakou, Christina; Park, Margriet Vdz; de Jong, Wim H; van Loveren, Henk; Vandebriel, Rob J; Geertsma, Robert E

    2016-01-01

    Nanomaterials (NMs) are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs) currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome activation, and hypersensitivity, are not readily detected by using current testing guidelines. Immunotoxicity of NMPs would be more accurately evaluated by an expanded testing strategy that is equipped to stratify applicable testing for the various types of NMPs.

  13. 77 FR 304 - New Postal Product

    Science.gov (United States)

    2012-01-04

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to add Priority Mail Contract 37 to the competitive product list... competitive product list.\\1\\ Priority mail [[Page 305

  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. Regulation – Do or Die: An Analysis of Factors Critical to New Product Development in a Regulatory Context

    Directory of Open Access Journals (Sweden)

    Clare O'Dwyer

    2017-04-01

    Full Text Available This study explores new product development in a strict regulatory and historically secretive environment. Adopting a systems perspective and a mixed methods approach in our research, we examine medical device development in Ireland. Findings indicate that the possession of a regulatory strategy expedites the rate of commercialization, so too does the generation of clear product definitions and marketing claims in the earliest developmental phases. Moreover, results suggest that if the regulated industry strengthens its culture for regulation by prioritizing regulation over speed to market, by encouraging cross-functional team collaborations, and by taking a more proactive approach in post-marketing surveillance activities, it has the potential to improve customer satisfaction and enhance product innovation. This study provides unique empirical data enriched by the homogeneity of its sample. It also contributes guidance to practitioners of new product development within a regulatory context.

  16. Gender-specific Regulatory Challenges to Product Approval: a panel discussion.

    Science.gov (United States)

    McGregor, Alyson J; Barr, Helen; Greenberg, Marna R; Safdar, Basmah; Wildgoose, Peter; Wright, David W; Hollander, Judd E

    2014-12-01

    On May 13, 2014, a 1-hour panel discussion session titled "Gender-specific Regulatory Challenges to Product Approval" was held during the Academic Emergency Medicine consensus conference, "Gender-specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes." The session sought to bring together leaders in emergency medicine (EM) research, authors, and reviewers in EM research publications, as well as faculty, fellows, residents, and students engaged in research and clinical practice. A panel was convened involving a representative from the Office of Women's Health of the U.S. Food and Drug Administration, two pharmaceutical executives, and a clinical EM researcher. The moderated discussion also involved audience members who contributed significantly to the dialogue. Historical background leading up to the session along with the main themes of the discussion are reproduced in this article. These revolve around sex- and gender-specific research, statistical analysis of sex and gender, clinical practice, financial costs associated with pharmaceutical development, adaptive design, and specific recommendations on the regulatory process as it affects the specialty of EM. © 2014 by the Society for Academic Emergency Medicine.

  17. 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...

  18. A global regulatory science agenda for vaccines.

    Science.gov (United States)

    Elmgren, Lindsay; Li, Xuguang; Wilson, Carolyn; Ball, Robert; Wang, Junzhi; Cichutek, Klaus; Pfleiderer, Michael; Kato, Atsushi; Cavaleri, Marco; Southern, James; Jivapaisarnpong, Teeranart; Minor, Philip; Griffiths, Elwyn; Sohn, Yeowon; Wood, David

    2013-04-18

    The Decade of Vaccines Collaboration and development of the Global Vaccine Action Plan provides a catalyst and unique opportunity for regulators worldwide to develop and propose a global regulatory science agenda for vaccines. Regulatory oversight is critical to allow access to vaccines that are safe, effective, and of assured quality. Methods used by regulators need to constantly evolve so that scientific and technological advances are applied to address challenges such as new products and technologies, and also to provide an increased understanding of benefits and risks of existing products. Regulatory science builds on high-quality basic research, and encompasses at least two broad categories. First, there is laboratory-based regulatory science. Illustrative examples include development of correlates of immunity; or correlates of safety; or of improved product characterization and potency assays. Included in such science would be tools to standardize assays used for regulatory purposes. Second, there is science to develop regulatory processes. Illustrative examples include adaptive clinical trial designs; or tools to analyze the benefit-risk decision-making process of regulators; or novel pharmacovigilance methodologies. Included in such science would be initiatives to standardize regulatory processes (e.g., definitions of terms for adverse events [AEs] following immunization). The aim of a global regulatory science agenda is to transform current national efforts, mainly by well-resourced regulatory agencies, into a coordinated action plan to support global immunization goals. This article provides examples of how regulatory science has, in the past, contributed to improved access to vaccines, and identifies gaps that could be addressed through a global regulatory science agenda. The article also identifies challenges to implementing a regulatory science agenda and proposes strategies and actions to fill these gaps. A global regulatory science agenda will enable

  19. Cracking the regulatory code of biosynthetic gene clusters as a strategy for natural product discovery.

    Science.gov (United States)

    Rigali, Sébastien; Anderssen, Sinaeda; Naômé, Aymeric; van Wezel, Gilles P

    2018-01-05

    The World Health Organization (WHO) describes antibiotic resistance as "one of the biggest threats to global health, food security, and development today", as the number of multi- and pan-resistant bacteria is rising dangerously. Acquired resistance phenomena also impair antifungals, antivirals, anti-cancer drug therapy, while herbicide resistance in weeds threatens the crop industry. On the positive side, it is likely that the chemical space of natural products goes far beyond what has currently been discovered. This idea is fueled by genome sequencing of microorganisms which unveiled numerous so-called cryptic biosynthetic gene clusters (BGCs), many of which are transcriptionally silent under laboratory culture conditions, and by the fact that most bacteria cannot yet be cultivated in the laboratory. However, brute force antibiotic discovery does not yield the same results as it did in the past, and researchers have had to develop creative strategies in order to unravel the hidden potential of microorganisms such as Streptomyces and other antibiotic-producing microorganisms. Identifying the cis elements and their corresponding transcription factors(s) involved in the control of BGCs through bioinformatic approaches is a promising strategy. Theoretically, we are a few 'clicks' away from unveiling the culturing conditions or genetic changes needed to activate the production of cryptic metabolites or increase the production yield of known compounds to make them economically viable. In this opinion article, we describe and illustrate the idea beyond 'cracking' the regulatory code for natural product discovery, by presenting a series of proofs of concept, and discuss what still should be achieved to increase the rate of success of this strategy. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Regulatory Control of Radiation Sources. Safety Guide (Arabic Edition)

    International Nuclear Information System (INIS)

    2012-01-01

    This Safety Guide is intended to assist States in implementing the requirements established in Safety Standards Series No. GS-R-1, Legal and Governmental Infrastructure for Nuclear, Radiation, Radioactive Waste and Transport Safety, for a national regulatory infrastructure to regulate any practice involving radiation sources in medicine, industry, research, agriculture and education. The Safety Guide provides advice on the legislative basis for establishing regulatory bodies, including the effective independence of the regulatory body. It also provides guidance on implementing the functions and activities of regulatory bodies: the development of regulations and guides on radiation safety; implementation of a system for notification and authorization; carrying out regulatory inspections; taking necessary enforcement actions; and investigating accidents and circumstances potentially giving rise to accidents. The various aspects relating to the regulatory control of consumer products are explained, including justification, optimization of exposure, safety assessment and authorization. Guidance is also provided on the organization and staffing of regulatory bodies. Contents: 1. Introduction; 2. Legal framework for a regulatory infrastructure; 3. Principal functions and activities of the regulatory body; 4. Regulatory control of the supply of consumer products; 5. Functions of the regulatory body shared with other governmental agencies; 6. Organization and staffing of the regulatory body; 7. Documentation of the functions and activities of the regulatory body; 8. Support services; 9. Quality management for the regulatory system.

  1. Delegation, Presidential Regimes, and Latin American Regulatory Agencies Delegación, regimenes presidenciales y agencias reguladoras en América Latina

    Directory of Open Access Journals (Sweden)

    Jacint Jordana

    2010-04-01

    Full Text Available During the 1990s, a large number of regulatory agencies were created or reformed in different sectors in Latin American countries. Almost all included political delegation mechanisms, intended as formal rules to enhance credible commitments to time-consistent policies. In this paper, using an original data set of agencies’ head tenure in the telecommunications and finance regulatory agencies, we discuss if these mechanisms worked as planned, and find a divergence between actual mandates and the formally established fixed terms, effected by means of systematic early resignations. Our findings reveal, however, some consistent patterns of behavior. Stronger legislative presidential power reduced effective delegation to some extent, and agencies’ organizational strengths protected them from patron-age. We also confirmed the existence of some significant differences be-tween the two sectors examined. Having slightly weaker delegation rules, delegation practices were also less effective in telecommunications than in financial services, contrary to expectations about credible commitments. Durante los años 1990, muchas agencias reguladoras fueron creadas o reformadas en diferentes sectores en los países latinoamericanos. Casi todas incluyeron mecanismos de delegación política, entendidos como reglas formales para mejorar los compromisos creíbles sobre políticas que requieren coherencia en el tiempo. En este trabajo, utilizando un conjunto de datos originales sobre los responsables de las agencias reguladoras de las telecomunicaciones y de las finanzas, se discute si estos mecanismos funcionaron como estaba previsto, identificándose una divergencia entre los mandatos reales y los términos formalmente establecidos, debido a la existencia de numerosas renuncias anticipadas. Nuestros hallazgos revelan, sin embargo, algunos patrones consistentes de comportamiento: un mayor poder presidencial sobre el legislativo reduce la delegación efectiva

  2. Advanced Therapy Medicinal Products in type I diabetes mellitus: technological and regulatory challenges

    Directory of Open Access Journals (Sweden)

    Camila Leal-Lopes

    2018-02-01

    Full Text Available Introduction: Type 1 Diabetes mellitus (T1DM is an autoimmune disorder which arises from the destruction of insulin-producing pancreatic β-cells. Currently, Brazil’s advanced therapy medicinal products (ATMP, developed for clinical research and therapeutic purposes, take place in the so-called Cellular Technology Centers (CTC, according to the Resolution nº. 9/2011 of the Collegiate Board of Directors (RDC, enacted by the National Health Surveillance Agency (Anvisa. Objective: This study was conducted with the main objective of describing and discussing the development of ATMP for T1DM treatment. Method: A qualitative research, narrative review and critical discussion of the literature were under taken. Results: ATMP promote new therapeutic approaches for Diabetes, holding great potential to restore the patients’ endogenous insulin secretion, improving their life quality, overcoming the chronic complications of Diabetes and reducing the socioeconomic burden. Nowadays, ATMP in T1DM comprise: a cell therapy; b gene therapy products; c tissue engineering and d ATMPassociated to biopharmaceutical products. Conclusions: Further research should contribute to stimulate public and private organizations to effectively act towards reducing the impact of Diabetes on individuals and the society as a whole. It is essential that Brazilian legislation closely follows the biotechnological developments, supporting the scientific progress and benefiting T1DM patients with modern and cutting-edge therapies.

  3. The political economy of productive sectors: Explaining regulatory initiatives in the fisheries and dairy sectors in Uganda

    DEFF Research Database (Denmark)

    Kjær, Anne Mette

    of regulation of the fisheries resource. In contrast, Ugandan milk production has boomed since the mid 1990s, and while the quality of the milk used to be highly questionable due to practices such as diluting milk and boiling it in sauce-pans, quality has gradually improved due to regulatory initiatives...

  4. 78 FR 11686 - Agency Information Collection Activities: Submission for the Office of Management and Budget (OMB...

    Science.gov (United States)

    2013-02-19

    ...: Submission for the Office of Management and Budget (OMB) Review; Comment Request AGENCY: Nuclear Regulatory... introduction of byproduct material into products or materials and transfer of the products or materials to..., Office of Information and Regulatory Affairs (3150-0001), NEOB-10202, Office of Management and Budget...

  5. [Future Regulatory Science through a Global Product Development Strategy to Overcome the Device Lag].

    Science.gov (United States)

    Tsuchii, Isao

    2016-01-01

    Environment that created "medical device lag (MDL)" has changed dramatically, and currently that term is not heard often. This was mainly achieved through the leadership of three groups: government, which determined to overcome MDL and took steps to do so; medical societies, which exhibited accountability in trial participation; and MD companies, which underwent a change in mindset that allowed comprehensive tripartite cooperation to reach the current stage. In particular, the global product development strategy (GPDS) of companies in a changing social environment has taken a new-turn with international harmonization trends, like Global Harmonization Task Force and International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. As a result, this evolution has created opportunities for treatment with cutting-edge MDs in Japanese society. Simultaneously, it has had a major impact on the planning process of GPDS of companies. At the same time, the interest of global companies has shifted to emerging economies for future potential profit since Japan no longer faces MDL issue. This economic trend makes MDLs a greater problem for manufacturers. From the regulatory science viewpoint, this new environment has not made it easy to plan a global strategy that will be adaptable to local societies. Without taking hasty action, flexible thinking from the global point of view is necessary to enable the adjustment of local strategies to fit the situation on the ground so that the innovative Japanese medical technology can be exported to a broad range of societies.

  6. [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.

  7. THE RESPONSIBILITY FOR PREVENTING AND DETECTING ACCOUNTING FRAUDS FROM THE VIEWPOINT OF SELF-REGULATORY AGENCIES IN TURKEY: DE JURE STATUS AND DE FACTO APPLICATION

    Directory of Open Access Journals (Sweden)

    Canol KANDEMİR

    2013-07-01

    Full Text Available TÜRKİYE’DE DÜZENLEYİCİ KURULUŞLAR AÇISINDAN MUHASEBE HİLELERİNİN ÖNLENMESİ VE ORTAYA ÇIKARILMASI SORUMLULUĞU: HUKUKÎ DURUM VE FİİLÎ UYGULAMAÖzet: Düzenleyici kuruluşların yaklaşımı ve uygulamaları muhasebe hilelerinin önlenmesi ve ortaya çıkarılması sorumluluğunun kapsamının açıklığa kavuşturulmasına yardımcı olabilmektedir. Bu kuruluşların kamunun büyük bir çoğunluğunu adîl ve yansız bir şekilde temsil edeceği varsayılmaktadır. Ayrıca aldıkları kararlar ve karar alma mantıkları hem araştırmacılara, hem de finansal bilgi kullanıcılarına olası hile şüphelileri, bu kuruluşların sorumlulardan özellikle önlemesi ve ortaya çıkarmasını istedikleri hile yöntemleri, hilelerin cezaî yönleri, hilelerin önlenmesi ve ortaya çıkarılmasında temel sorumluluklar ve denetim beklenti boşluğu konularında önemli ipuçları verebilmektedir. Yine bunlar ilgili standart, yasa ve diğer düzenlemelerin oluşturulması ve uygulanmasında önemli etki sahibi olmaktadır. Bu nedenle, bağımsız denetimle ilgili faktörleri de kapsayan bir dizi değişken ile muhasebe hileleri arasında istatistiksel olarak anlamlı bir ilişki olup olmadığını sınayan bir çalışma yapılmış ve sonuç olarak Türkiye’deki düzenleyici kuruluşun muhasebe hilelerinin önlenmesi ve ortaya çıkarılması sorumluluğunu aynı tarafa, müşteri işletme ve yönetimine yüklediği bulunmuştur. Araştırmanın bulguları Türkiye’de bir denetim-beklenti boşluğu olmadığına da işaret etmektedir.THE RESPONSIBILITY FOR PREVENTING AND DETECTING ACCOUNTING FRAUDS FROM THE VIEWPOINT OF SELF-REGULATORY AGENCIES IN TURKEY: DE JURE STATUS AND DE FACTO APPLICATIONAbstract: Self-regulatory agencies’ way of understanding and practices can help clarify the scope of the responsibility for preventing and detecting frauds. They are assumed to represent a vast majority of the public in an unbiased and

  8. Regulatory controls for NORM contamination: Emerging issues and strategies

    International Nuclear Information System (INIS)

    Wennerberg, Linda

    1992-01-01

    Naturally occurring and accelerator-produced radioactive material (NORM) faces the increasing likelihood of federal or state regulatory control. Public concern and limited preliminary survey data fuel the debate over the necessity, approach, and jurisdiction of a NORM regulatory strategy. This debate requires the resolution of technical controversies and potentially competing state and federal agency interests. An additional facet of the debate is the impact of regulation upon traditionally non-nuclear industries, such as oil and gas production. Regulatory response has been initiated in several states, such as Louisiana's controls on equipment used in oil and gas production, to control specific industrial activities which generate NORM. A more comprehensive, generic federal strategy to control NORM contamination is also under review by the Environmental Protection Agency. This paper will detail the emerging technical issues, federal and state regulatory strategies under consideration, and evaluate the efficacy of selected regulatory approaches. (author)

  9. Recombinant biologic products versus nutraceuticals from plants – a regulatory choice?

    Science.gov (United States)

    Drake, Pascal M. W.; Szeto, Tim H.; Paul, Mathew J.; Teh, Audrey Y.‐H.

    2016-01-01

    Biotechnology has transformed the potential for plants to be a manufacturing source of pharmaceutical compounds. Now, with transgenic and transient expression techniques, virtually any biologic, including vaccines and therapeutics, could be manufactured in plants. However, uncertainty over the regulatory path for such new pharmaceuticals has been a deterrent. Consideration has been given to using alternative regulatory paths, including those for nutraceuticals or cosmetic agents. This review will consider these possibilities, and discuss the difficulties in establishing regulatory guidelines for new pharmaceutical manufacturing technologies. PMID:27297459

  10. 78 FR 43246 - New Postal Product

    Science.gov (United States)

    2013-07-19

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2013-15; Order No. 1779] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service... competitive products by market dominant products. Id. II. Notice of Filing Interested persons may submit...

  11. Regulatory role of melatonin and BMP-4 in prolactin production by rat pituitary lactotrope GH3 cells.

    Science.gov (United States)

    Ogura-Ochi, Kanako; Fujisawa, Satoshi; Iwata, Nahoko; Komatsubara, Motoshi; Nishiyama, Yuki; Tsukamoto-Yamauchi, Naoko; Inagaki, Kenichi; Wada, Jun; Otsuka, Fumio

    2017-08-01

    The effects of melatonin on prolactin production and its regulatory mechanism remain uncertain. We investigated the regulatory role of melatonin in prolactin production using rat pituitary lactotrope GH3 cells by focusing on the bone morphogenetic protein (BMP) system. Melatonin receptor activation, induced by melatonin and its receptor agonist ramelteon, significantly suppressed basal and forskolin-induced prolactin secretion and prolactin mRNA expression in GH3 cells. The melatonin MT2 receptor was predominantly expressed in GH3 cells, and the inhibitory effects of melatonin on prolactin production were reversed by treatment with the receptor antagonist luzindole, suggesting functional involvement of MT2 action in the suppression of prolactin release. Melatonin receptor activation also suppressed BMP-4-induced prolactin expression by inhibiting phosphorylation of Smad and transcription of the BMP-target gene Id-1, while BMP-4 treatment upregulated MT2 expression. Melatonin receptor activation suppressed basal, BMP-4-induced and forskolin-induced cAMP synthesis; however, BtcAMP-induced prolactin mRNA expression was not affected by melatonin or ramelteon, suggesting that MT2 activation leads to inhibition of prolactin production through the suppression of Smad signaling and cAMP synthesis. Experiments using intracellular signal inhibitors revealed that the ERK pathway is, at least in part, involved in prolactin induction by GH3 cells. Thus, a new regulatory role of melatonin involving BMP-4 in prolactin secretion was uncovered in lactotrope GH3 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Readability assessment of package inserts of biological medicinal products from the European medicines agency website.

    Science.gov (United States)

    Piñero-López, Ma Ángeles; Modamio, Pilar; Lastra, Cecilia F; Mariño, Eduardo L

    2014-07-01

    Package inserts that accompany medicines are a common source of information aimed at patients and should match patient abilities in terms of readability. Our objective was to determine the degree of readability of the package inserts for biological medicinal products commercially available in 2007 and compare them with the readability of the same package inserts in 2010. A total of 33 package inserts were selected and classified into five groups according to the type of medicine: monoclonal antibody-based products, cytokines, therapeutic enzymes, recombinant blood factors and other blood-related products, and recombinant hormones. The package inserts were downloaded from the European Medicines Agency website in 2007 and 2010. Readability was evaluated for the entire text of five of the six sections of the package inserts and for the 'Annex' when there was one. Three readability formulas were used: SMOG (Simple Measure of Gobbledygook) grade, Flesh-Kincaid grade level, and Szigriszt's perspicuity index. No significant differences were found between the readability results for the 2007 package inserts and those from 2010 according to any of the three readability indices studied (p>0.05). However, there were significant differences (preadability scores of the sections of the package inserts in both 2007 and 2010. The readability of the package inserts was above the recommended sixth grade reading level (ages 11-12) and may lead to difficulties of understanding for people with limited literacy. All the sections should be easy to read and, therefore, the readability of the medicine package inserts studied should be improved.

  13. Promoting Implementation of Safety Culture in Nuclear Application for Industrial Facilities; an Important Role of Nuclear Energy Regulatory Agency in Indonesia

    Energy Technology Data Exchange (ETDEWEB)

    Setianingsih, Lilis Susanti [KINS-KAIST Master Degree Program, Daejeon (Korea, Republic of)

    2012-03-15

    Implementation of nuclear energy for industrial purposes has reached its highest peak. BAPETEN, as Nuclear Energy Regulatory Agency of Indonesia has published regulations regarding nuclear energy utilization. As high risk associating such utilization requires direct and thoroughly supervision in order to assure its compliance to safety and security aspect, procedures related to operational activities must by fully applied. Radiation Protection Program as one type of procedures that must be available in nuclear energy utilization operation is intended to provide operators specifically technical guidance to avoid undesired negative effects of incidents or accidents. It is the responsibility of managerial level in a company to provide the procedures and to further supervise their application in the field. Radiation workers, those are all employees working in or within radiation area must understand how to execute the procedures properly. The radiation protection program is intended to protect workers, member of community and property as well as the environment from the negative impacts of nuclear utilization operational due to its radiation exposure. Safety culture, a compound of nature derived from behavior of organization and people within the organization to pay a full attention and give main priority in radiation safety matters, is expected to be achieved by implementing the radiation protection program as safety habits at the work place. It requires a management commitment to ensure that all aspect in safety and, whenever necessary, security are accomplished within the radiation protection program in order to build a safety culture in a radiation work place. Government Regulation No. 33 2007 about Safety for Ionizing Radiation and Security for Radioactive Source and Government Regulation No. 29 2008 regarding Licensing for Utilization of Ionizing Radiation and Nuclear Material present regulation and arrangement related to radiation protection program as a basic

  14. 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

  15. Promoting Implementation of Safety Culture in Nuclear Application for Industrial Facilities; an Important Role of Nuclear Energy Regulatory Agency in Indonesia

    International Nuclear Information System (INIS)

    Setianingsih, Lilis Susanti

    2012-01-01

    Implementation of nuclear energy for industrial purposes has reached its highest peak. BAPETEN, as Nuclear Energy Regulatory Agency of Indonesia has published regulations regarding nuclear energy utilization. As high risk associating such utilization requires direct and thoroughly supervision in order to assure its compliance to safety and security aspect, procedures related to operational activities must by fully applied. Radiation Protection Program as one type of procedures that must be available in nuclear energy utilization operation is intended to provide operators specifically technical guidance to avoid undesired negative effects of incidents or accidents. It is the responsibility of managerial level in a company to provide the procedures and to further supervise their application in the field. Radiation workers, those are all employees working in or within radiation area must understand how to execute the procedures properly. The radiation protection program is intended to protect workers, member of community and property as well as the environment from the negative impacts of nuclear utilization operational due to its radiation exposure. Safety culture, a compound of nature derived from behavior of organization and people within the organization to pay a full attention and give main priority in radiation safety matters, is expected to be achieved by implementing the radiation protection program as safety habits at the work place. It requires a management commitment to ensure that all aspect in safety and, whenever necessary, security are accomplished within the radiation protection program in order to build a safety culture in a radiation work place. Government Regulation No. 33 2007 about Safety for Ionizing Radiation and Security for Radioactive Source and Government Regulation No. 29 2008 regarding Licensing for Utilization of Ionizing Radiation and Nuclear Material present regulation and arrangement related to radiation protection program as a basic

  16. Launching a new food product or dietary supplement in the United States: industrial, regulatory, and nutritional considerations.

    Science.gov (United States)

    Finley, John Weldon; Finley, John Wescott; Ellwood, Kathleen; Hoadley, James

    2014-01-01

    Launching a new food/dietary supplement into the US market can be a confusing process to those unfamiliar with the food industry. Industry capability and product specifications are initial determinants of whether a candidate product can be manufactured in a reproducible manner and whether pilot production can be brought up to the market scale. Regulatory issues determine how a product can be produced and marketed; the primary federal institutions involved in regulations are the US Department of Agriculture, the Food and Drug Administration, and the Federal Trade Commission. A primary distinction is made between food and drugs, and no product may enter the food market if it is in part or whole a drug. Product safety is a major concern, and myriad regulations govern the determination of safety. New foods/dietary supplements are often marketed by health claims or structure/function claims, and there are specific regulations pertaining to claims. Not understanding the regulatory issues involved in developing a new product or failing to comply with associated regulations can have legal and financial repercussions.

  17. Induction of bacteriocin production by coculture is widespread among plantaricin-producing Lactobacillus plantarum strains with different regulatory operons.

    Science.gov (United States)

    Maldonado-Barragán, Antonio; Caballero-Guerrero, Belén; Lucena-Padrós, Helena; Ruiz-Barba, José Luis

    2013-02-01

    We describe the bacteriocin-production phenotype in a group of eight singular bacteriocinogenic Lactobacillus plantarum strains with three distinct genotypes regarding the plantaricin locus. Genotyping of these strains revealed the existence of two different plantaricin-production regulatory operons, plNC8-plNC8HK-plnD or plnABCD, involving three-component systems controlled each of them by a specific autoinducer peptide (AIP), i.e. PLNC8IF or PlnA. While all of the strains produced antimicrobial activity when growing on solid medium, most of them halted this production when cultured in broth, thus reflecting the functionality of regulatory mechanisms. Antimicrobial activity in broth cultures was re-established or enhanced when the specific AIP was added to the culture or by coculturing with specific bacterial strains. The latter trait appeared to be widespread in bacteriocinogenic L. plantarum strains independently of the regulatory system used to regulate bacteriocin production or the specific bacteriocins produced. The induction spectrum through coculture, i.e. the pattern of bacterial strains able to induce bacteriocin production, was characteristic of each individual L. plantarum strain. Also, the ability of some bacteria to induce bacteriocin production in L. plantarum by coculture appeared to be strain specific. The fact that induction of bacteriocin production by coculturing appeared to be a common feature in L. plantarum can be exploited accordingly to enhance the viability of this species in food and feed fermentations, as well as to contribute to probiotic functionality when colonising the gastrointestinal tract. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. COST EFFECTIVE REGULATORY APPROACHES TO ENHANCE DOMESTIC OIL & GAS PRODUCTION AND ENSURE THE PROTECTION OF THE ENVIRONMENT

    Energy Technology Data Exchange (ETDEWEB)

    Ben Grunewald; Paul Jehn; Tom Gillespie; Ben Binder

    2004-12-21

    The Environmental Information Management Suite/Risk Based Data Management System (EIMS/RBDMS) and Cost Effective Regulatory Approach (CERA) programs continue to be successful. All oil and gas state regulatory programs participate in these efforts. Significant accomplishments include: streamline regulatory approaches, enhancing environmental protection, and making oil and gas data available via the Internet. Oil and gas companies worldwide now have access to data on state web sites. This reduces the cost of exploration and enables companies to develop properties in areas that would have been cost prohibited for exploration. Early in project, GWPC and State Oil and Gas agencies developed the EIMS and CERA strategic plan to prioritize long term development and implementation. The planning process identifies electronic commerce and coal bed methane as high priorities. The group has involved strategic partners in industry and government to develop a common data exchange process. Technical assistance to Alaska continues to improve their program management capabilities. New initiatives in Alaska include the development of an electronic permit tracking system. This system allows managers to expedite the permitting process. Nationwide, the RBDMS system is largely completed with 22 states and one Indian Nation now using this nationally accepted data management system. Additional remaining tasks include routine maintenance and the installation of the program upon request for the remaining oil and gas states. The GWPC in working with the BLM and MMS to develop an XML schema to facilitate electronic permitting and reporting (Appendix A, B, and C). This is a significant effort and, in years to come, will increase access to federal lands by reducing regulatory barriers. The new initiatives are coal bed methane and e-commerce. The e-commerce program will provide industry and BLM/MMS access to the millions of data points housed in the RBDMS system. E-commerce will streamline

  19. [Regulatory science: modern trends in science and education for pharmaceutical products].

    Science.gov (United States)

    Beregovykh, V V; Piatigorskaia, N V; Aladysheva, Zh I

    2012-01-01

    This article reviews modern trends in development of new instruments, standards and approaches to drugs safety, efficacy and quality assessment in USA and EU that can be called by unique term--"regulatory science" which is a new concept for Russian Federation. New education programs (curricula) developed by USA and EU universities within last 3 years are reviewed. These programs were designed in order to build workforce capable to utilize science approach for drug regulation. The principal mechanisms for financing research in regulatory science used by Food and Drug Administration are analyzed. There are no such science and relevant researches in Russian Federation despite the high demand as well as needs for the system for higher education and life-long learning education of specialists for regulatory affairs (or compliance).

  20. Defining products for a new health technology assessment agency in Madrid, Spain: a survey of decision makers.

    Science.gov (United States)

    Andradas, Elena; Blasco, Juan-Antonio; Valentín, Beatriz; López-Pedraza, María-José; Gracia, Francisco-Javier

    2008-01-01

    The aim of this study was to explore the needs and requirements of decision makers in our regional healthcare system for health technology assessment (HTA) products to support portfolio development planning for a new HTA agency in Madrid, Spain. A Delphi study was conducted during 2003. Questionnaires were developed based on a review of products and services offered by other agency members of the International Network of Agencies for Health Technology Assessment, and included preference and prioritization questions to evaluate twenty-two different products and services. The initial Delphi panel involved eighty-seven experts from twenty-one public hospitals, eleven primary healthcare centers, six private hospitals, and eight departments of the Regional Ministry of Health of the Community of Madrid. The global participation rate was 83.9 percent. Ten of the twenty-two possible products were rated of high interest by more than 80 percent of respondents. Important differences in preferences and priorities were detected across different settings. Public hospitals and primary healthcare centers shared a more "micro" perspective, preferring classic technology-centered HTA products, whereas private hospitals and Ministry representatives demanded more "macro" products and services such as organizational model and information system assessments. The high participation rate supports the representativeness of the results for our regional context. The strategic development of an HTA portfolio based on decision makers' needs and requirements as identified in this type of exercise should help achieve a better impact on policy development and decision making.

  1. SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea.

    Science.gov (United States)

    Kirm, Benjamin; Magdevska, Vasilka; Tome, Miha; Horvat, Marinka; Karničar, Katarina; Petek, Marko; Vidmar, Robert; Baebler, Spela; Jamnik, Polona; Fujs, Štefan; Horvat, Jaka; Fonovič, Marko; Turk, Boris; Gruden, Kristina; Petković, Hrvoje; Kosec, Gregor

    2013-12-17

    D, SACE_5599 is involved in morphological development of S. erythraea, suggesting a very close relationship between secondary metabolite biosynthesis and morphological differentiation in this organism. While the mode of action of SACE_5599 remains to be elucidated, the manipulation of this gene clearly shows potential for improvement of erythromycin production in S. erythraea in industrial setting. We have also demonstrated the applicability of the comparative proteomics approach for identifying new regulatory elements involved in biosynthesis of secondary metabolites in industrial conditions.

  2. Review of hazardous chemical regulation at nuclear facilities by the Nuclear Regulatory Commission and other federal agencies. Hearing before a Subcommittee of the Committee on Government Operations, House of Representatives, Ninety-Ninth Congress, Second Session, March 14, 1986

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    Seven witnesses from agencies and the nuclear industry testified on the status of chemical regulation at nuclear facilities, the potential for accidents, and the quality of emergency plans in the event of a release of chemical substances. Impetus for the review came from incidents at Kerr-McGhee's Sequoyah plant in Oklahoma and the release of uranium hexafluoride, as well as a pattern of accidents which occur after the potential hazard has already been identified. The witnesses included Richard Krimm of the Federal Emergency Management Agency, James Makris of the Environmental Protection Agency, John Miles of the Occupational Safety and Health Administration, Nunxio Palladino of the Nuclear Regulatory Commission, and representatives of DOE and Kerr-McGee. Additional materials submitted for the record follows the testimony

  3. Reality Monitoring and Feedback Control of Speech Production Are Related Through Self-Agency.

    Science.gov (United States)

    Subramaniam, Karuna; Kothare, Hardik; Mizuiri, Danielle; Nagarajan, Srikantan S; Houde, John F

    2018-01-01

    Self-agency is the experience of being the agent of one's own thoughts and motor actions. The intact experience of self-agency is necessary for successful interactions with the outside world (i.e., reality monitoring) and for responding to sensory feedback of our motor actions (e.g., speech feedback control). Reality monitoring is the ability to distinguish internally self-generated information from outside reality (externally-derived information). In the present study, we examined the relationship of self-agency between lower-level speech feedback monitoring (i.e., monitoring what we hear ourselves say) and a higher-level cognitive reality monitoring task. In particular, we examined whether speech feedback monitoring and reality monitoring were driven by the capacity to experience self-agency-the ability to make reliable predictions about the outcomes of self-generated actions. During the reality monitoring task, subjects made judgments as to whether information was previously self-generated (self-agency judgments) or externally derived (external-agency judgments). During speech feedback monitoring, we assessed self-agency by altering environmental auditory feedback so that subjects listened to a perturbed version of their own speech. When subjects heard minimal perturbations in their auditory feedback while speaking, they made corrective responses, indicating that they judged the perturbations as errors in their speech output. We found that self-agency judgments in the reality-monitoring task were higher in people who had smaller corrective responses ( p = 0.05) and smaller inter-trial variability ( p = 0.03) during minimal pitch perturbations of their auditory feedback. These results provide support for a unitary process for the experience of self-agency governing low-level speech control and higher level reality monitoring.

  4. 77 FR 50729 - New Postal Product

    Science.gov (United States)

    2012-08-22

    ... POSTAL REGULATORY COMMISSION [Docket Nos. MC2012-44; Order No. 1435] New Postal Product AGENCY... Service request for two related changes to the product lists. The changes involve removing one product from the market dominant product list and adding a nearly identical product to the competitive product...

  5. Hurdles in tissue engineering/regenerative medicine product commercialization: a pilot survey of governmental funding agencies and the financial industry.

    Science.gov (United States)

    Bertram, Timothy A; Tentoff, Edward; Johnson, Peter C; Tawil, Bill; Van Dyke, Mark; Hellman, Kiki B

    2012-11-01

    The Tissue Engineering and Regenerative Medicine International Society of the Americas (TERMIS-AM) Industry Committee conducted a semiquantitative opinion survey in 2010 to delineate potential hurdles to commercialization perceived by the TERMIS constituency groups that participate in the stream of technology commercialization (academia, start-up companies, development-stage companies, and established companies). A significant hurdle identified consistently by each group was access to capital for advancing potential technologies into development pathways leading to commercialization. A follow-on survey was developed by the TERMIS-AM Industry Committee to evaluate the financial industry's perspectives on investing in regenerative medical technologies. The survey, composed of 15 questions, was developed and provided to 37 investment organizations in one of three sectors (governmental, private, and public investors). The survey was anonymous and confidential with sector designation the only identifying feature of each respondent's organization. Approximately 80% of the survey was composed of respondents from the public (n=14) and private (n=15) sectors. Each respondent represents one investment organization with the potential of multiple participants participating to form the organization's response. The remaining organizations represented governmental agencies (n=8). Results from this survey indicate that a high percentage ($2MM into regenerative medical companies at the different stages of a company's life cycle. Investors recognized major hurdles to this emerging industry, including regulatory pathway, clinical translation, and reimbursement of these new products. Investments in regenerative technologies have been cyclical over the past 10-15 years, but investors recognized a 1-5-year investment period before the exit via Merger and Acquisition (M&A). Investors considered musculoskeletal products and their top technology choice with companies in the clinical stage

  6. 78 FR 79024 - New Postal Product

    Science.gov (United States)

    2013-12-27

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2011-50; Order No. 1922] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service... new product name. Id. at 1 n.1. Attachment A--a redacted copy of the amendment to the existing...

  7. 78 FR 21632 - International Mail Product

    Science.gov (United States)

    2013-04-11

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2013-59; Order No. 1692] International Mail Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal... have the Agreement included within the existing IBRS Competitive Contract 3 product on grounds of...

  8. 78 FR 76333 - New Postal Product

    Science.gov (United States)

    2013-12-17

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2011-4; Order No. 1901] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service... not materially affect the cost coverage'' of the product. Id. The Postal Service seeks to incorporate...

  9. Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis

    Science.gov (United States)

    Fu, Wenyu; Hu, Wenhuo; Shi, Lei; Mundra, Jyoti Joshi; Xiao, GuoZhi; Dustin, Michael L.; Liu, Chuan-ju

    2017-01-01

    Progranulin (PGRN) restrains inflammation and is therapeutic against inflammatory arthritis; however, the underlying immunological mechanism remains unknown. In this study, we demonstrated that anti-inflammatory cytokine IL-10 was a critical mediator for PGRN-mediated anti-inflammation in collagen-induced arthritis by using PGRN and IL-10 genetically modified mouse models. IL-10 green fluorescent protein reporter mice revealed that regulatory T (Treg) cells were the predominant source of IL-10 in response to PGRN. In addition, PGRN-mediated expansion and activation of Treg cells, as well as IL-10 production, depends on JNK signaling, but not on known PGRN-activated ERK and PI3K pathways. Furthermore, microarray and chromatin immunoprecipitation sequencing screens led to the discovery of forkhead box protein O4 and signal transducer and activator of transcription 3 as the transcription factors required for PGRN induction of IL-10 in Treg cells. These findings define a previously unrecognized signaling pathway that underlies IL-10 production by PGRN in Treg cells and present new insights into the mechanisms by which PGRN resolves inflammation in inflammatory conditions and autoimmune diseases, particularly inflammatory arthritis.—Fu, W., Hu, W., Shi, L., Mundra, J. J. Xiao, G., Dustin, M. L., Liu, C. Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis. PMID:28011648

  10. 75 FR 7526 - Withdrawal of Regulatory Guide

    Science.gov (United States)

    2010-02-19

    ...'s Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are... NUCLEAR REGULATORY COMMISSION [NRC-2010-0052] Withdrawal of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 1.56, ``Maintenance of Water Purity in Boiling...

  11. The Agency's publications

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1961-09-15

    With regard to bulk and substance, by far the most important part of the IAEA publishing is the publication of the proceedings of the scientific conferences, symposia and seminars held by the Agency, either alone or in co-operation with the United Nations specialized agencies or scientific unions. At present, the production time between the holding of a conference and the publication of its proceedings by the Agency is between 9 and 12 months. Another important group of publications is the directories, safety manuals and monographs Of the Directory of Nuclear Reactors, three volumes have so far been issued, in which detailed information is given about the power, research, test and experimental reactors in operation or under construction in different parts of the world. International Directory of Radioisotope Teletherapy equipment lists available equipment with considerable technical data and approximate prices. In the 'Safety Series', are included manuals on the safe handling of radioisotopes, the safe transport of radioactive materials, etc., which contain the regulations applied to the Agency's own operations or to operations assisted by the Agency. The Series also includes manuals which are informative rather than regulatory, such as the Health Physics and Medical Addenda to the manual on the Safe Handling of Radioisotopes, a report on radioactive waste disposal into the sea, a guide for the safe operation of critical assemblies and research reactors, notes on the Regulations for the Safe Transport of Radioactive Materials, and a manual on the use of film-badge dosimeters. The Review Series consists of monographs on different subjects written by experts in the particular fields. They are published in their original language and in some cases a translation into one or even two other working languages is included. The 'Bibliographical Series' includes bibliographies of the world-wide literature in different branches of nuclear science and technology. One of the

  12. The Agency's publications

    International Nuclear Information System (INIS)

    1961-01-01

    With regard to bulk and substance, by far the most important part of the IAEA publishing is the publication of the proceedings of the scientific conferences, symposia and seminars held by the Agency, either alone or in co-operation with the United Nations specialized agencies or scientific unions. At present, the production time between the holding of a conference and the publication of its proceedings by the Agency is between 9 and 12 months. Another important group of publications is the directories, safety manuals and monographs Of the Directory of Nuclear Reactors, three volumes have so far been issued, in which detailed information is given about the power, research, test and experimental reactors in operation or under construction in different parts of the world. International Directory of Radioisotope Teletherapy equipment lists available equipment with considerable technical data and approximate prices. In the 'Safety Series', are included manuals on the safe handling of radioisotopes, the safe transport of radioactive materials, etc., which contain the regulations applied to the Agency's own operations or to operations assisted by the Agency. The Series also includes manuals which are informative rather than regulatory, such as the Health Physics and Medical Addenda to the manual on the Safe Handling of Radioisotopes, a report on radioactive waste disposal into the sea, a guide for the safe operation of critical assemblies and research reactors, notes on the Regulations for the Safe Transport of Radioactive Materials, and a manual on the use of film-badge dosimeters. The Review Series consists of monographs on different subjects written by experts in the particular fields. They are published in their original language and in some cases a translation into one or even two other working languages is included. The 'Bibliographical Series' includes bibliographies of the world-wide literature in different branches of nuclear science and technology. One of the

  13. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.

    Directory of Open Access Journals (Sweden)

    Liana Verinaud

    Full Text Available Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola, a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+. We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation and stimulation of regulatory T cells (in chronic inflammation. New studies must be

  14. Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma.

    Science.gov (United States)

    Halwani, Rabih; Sultana, Asma; Vazquez-Tello, Alejandro; Jamhawi, Amer; Al-Masri, Abeer A; Al-Muhsen, Saleh

    2017-11-01

    In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils. Peripheral blood neutrophils isolated from asthmatics were stimulated with IL-21, IL-23, and IL-6 cytokines and their ability to produce IL-17A and IL-17F was determined relative to healthy controls. Signal transducer and activator of transcription 3 (STAT3) phosphorylation levels were measured in stimulated neutrophil using flow cytometry. The requirement for STAT3 phosphorylation was determined by blocking its activation using a specific chemical inhibitor. Stimulating asthmatic neutrophils with IL-21, 23, and 6 enhanced the production of IL-17A and IL-17F at significantly higher levels comparatively to healthy controls. Stimulating neutrophils with IL-21, IL-23, and IL-6 cytokines enhanced STAT3 phosphorylation, in all cases. Interestingly, inhibiting STAT3 phosphorylation using a specific chemical inhibitor dramatically blocked the ability of neutrophils to produce IL-17, demonstrating that STAT3 activation is the major factor mediating IL-17 gene expression. These findings suggest that neutrophil infiltration in lungs of severe asthmatics may represent an important source of pro-inflammatory IL-17A and -F cytokines, a production enhanced by Th-17 regulatory cytokines, and thus providing a feedback mechanism that sustains inflammation. Our results suggest that STAT3 pathway could be a potential target for regulating neutrophilic inflammation during severe asthma.

  15. Corporate Social Responsibility and Labour Agency

    DEFF Research Database (Denmark)

    Lund-Thomsen, Peter; Coe, Neil M.

    2015-01-01

    to which the measures advocated in a new, emerging policy paradigm on CSR in GPNs enabled labour agency at Nike’s main football supplier factory in Pakistan. We argue that while such CSR policies can create enhanced space for labour agency, that potential agency is also shaped (i) by wider economic forces......This article examines the circumstances under which corporate social responsibility (CSR) initiatives facilitate and/or constrain labour agency in global production networks (GPNs). Using a case study of Nike’s CSR approach in the football manufacturing industry of Pakistan, we explore the extent...... within the global economy and (ii) relationships with local/national actors and regulatory frameworks. Understanding the intersection of these dimensions becomes vital to interpreting the potential for, and activation of, labour agency within CSR-influenced GPNs....

  16. Production-Worthy USJ Formation by Self-Regulatory Plasma Doping Method

    International Nuclear Information System (INIS)

    Sasaki, Y.; Ito, H.; Okashita, K.; Tamura, H.; Jin, C. G.; Mizuno, B.; Okumura, T.; Aiba, I.; Sauddin, H.; Iwai, H.; Fukagawa, Y.; Tsutsui, K.

    2006-01-01

    A new method of plasma doping that achieves tight control on dosimetry and uniformity has been developed. It uses a self-regulatory behavior of plasma processes that brings high accuracy on dose control and uniformity within 1.5%. The largest advantage of this self-regulatory plasma doping (SRPD) is that the accuracy of the process control is much less dependent on the uniformity of the plasma, which makes a revolutionary difference to the plasma process as it becomes free from the primary hardware constraint. A typical doping of boron using B2H6/He gas mixture at dose of 1x1015 ions/cm2 can achieve a uniformity of less than 1.5% across a 300mm silicon wafer when the plasma uniformity above the wafer plane is as poor as 10%. The SRPD process also forms very abrupt junctions such as less than 2nm/decade at the junction depth of 10nm due to an instantaneous amorphization of the wafer surface within the first 5 seconds of the process duration. Combined with the throughput advantage at low energy against the conventional ion implantation, the SRPD offers an ideal performance for USJ formation for 45nm technology node and beyond

  17. What's in a name? Developing definitions for common health technology assessment product types of the International Network of Agencies for Health Technology Assessment (inahta).

    Science.gov (United States)

    Merlin, Tracy; Tamblyn, David; Ellery, Benjamin

    2014-10-01

    A mapping exercise was undertaken to determine how HTA is being described and conducted across the International Network of Agencies for Health Technology Assessment (INAHTA), with the aim of harmonizing terminologies and approaches. Three progressive surveys were undertaken. In 2010, INAHTA agencies were asked to provide details on all of their HTA products. In 2013, additional information was sought on key methodological characteristics of five of the most common HTA product types. Subsequently, final agreement was sought on three proposed product types. Forty-five HTA agencies responded to at least one of the surveys. In 2010, twenty-one agencies reported publishing over seventy named HTA products. Core domains associated with full HTA reports were reported by a third of agencies but were labeled differently, so products were classified according to product type (n = 17). Agencies producing short, tailored products increased between 2010 and 2013, with the publication of rapid reviews doubling from 33 percent to 66 percent. In 2013, half of the agencies adapted their common HTA products from documents produced by other agencies. A consensus (>70 percent) was achieved on definitions for HTA reports, mini-HTAs, and rapid reviews. The product label for an HTA is not always indicative of its content. Terminology has, therefore, been agreed to make explicit the trade-off between rigor and timeliness in three common HTA product types. An INAHTA Product Type (IPT) Mark has been created to identify each of these. It is hoped this will further facilitate HTA adaptation between agencies and reduce duplication of effort.

  18. Impacts of different regulatory regimes in the unitization of production; Impactos dos diferentes regimes regulatorios na individualizacao da producao

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Vinicius Farias; Moreira, Robson Prates [Petroleo Brasileiro S.A. (PETROBRAS), Rio de Janeiro, RJ (Brazil)

    2012-07-01

    The unitization process is required in most regulatory models around the world when it identifies that a reservoir straddles to out of the contracted area. This procedure aims to ensure a greater exploitation of petroleum. In Brazil is no different; however there are still many ambiguities in this process. The introduction of new tax regimes in the country broadened the doubts, as we may have a reservoir straddling between concession, production sharing, assignment of rights areas and areas not yet contracted. The objective of the present paper is to explore the uncertainties that must be addressed by the oil and gas sector in order to ensure low legal, regulatory and fiscal risks in the oil industry. The main topics discussed are the rules for production allocation, reserves and expenditures, the ANP and PPSA roles' conflicts, restriction of parties' rights, adjustment of contractual rules and also mitigate or eliminate economic, financial and fiscal uncertainties. This article does not propose solutions to all lacks raised. (author)

  19. Introduction to the Unified Agenda of Federal Regulatory and Deregulatory Actions

    Science.gov (United States)

    2010-04-26

    ... Regulatory Commission Federal Housing Finance Agency Federal Maritime Commission Federal Mediation and... that the Regulatory Flexibility Act may require a Regulatory Flexibility Analysis, actions selected for.... Regulatory Flexibility Analysis Required -- whether an analysis is required by the Regulatory Flexibility Act...

  20. Regulatory Monitoring of Fortified Foods: Identifying Barriers and Good Practices

    Science.gov (United States)

    Rowe, Laura A; Vossenaar, Marieke; Garrett, Greg S

    2015-01-01

    While fortification of staple foods and condiments has gained enormous global traction, poor performance persists throughout many aspects of implementation, most notably around the critical element of regulatory monitoring, which is essential for ensuring foods meet national fortification standards. Where coverage of fortified foods is high, limited nutritional impact of fortification programs largely exists due to regulatory monitoring that insufficiently identifies and holds producers accountable for underfortified products. Based on quality assurance data from 20 national fortification programs in 12 countries, we estimate that less than half of the samples are adequately fortified against relevant national standards. In this paper, we outline key findings from a literature review, key informant interviews with 11 fortification experts, and semi-quantitative surveys with 39 individuals from regulatory agencies and the food fortification industry in 17 countries on the perceived effectiveness of regulatory monitoring systems and barriers to compliance against national fortification standards. Findings highlight that regulatory agencies and industry disagree on the value that enforcement mechanisms have in ensuring compliance against standards. Perceived political risk of enforcement and poorly resourced inspectorate capacity appear to adversely reinforce each other within an environment of unclear legislation to create a major hurdle for improving overall compliance of fortification programs against national standards. Budget constraints affect the ability of regulatory agencies to create a well-trained inspector cadre and improve the detection and enforcement of non-compliant and underfortified products. Recommendations to improve fortification compliance include improving technical capacity; ensuring sustained leadership, accountability, and funding in both the private and the public sectors; and removing political barriers to ensure consistent detection of

  1. Spontaneously Reported Adverse Reactions for Herbal Medicinal Products and Natural Remedies in Sweden 2007-15: Report from the Medical Products Agency.

    Science.gov (United States)

    Svedlund, Erika; Larsson, Maria; Hägerkvist, Robert

    2017-06-01

    In relation to the extensive use of herbal medicinal products in self-care, the safety information is limited and there is a need for improvement. This study describes spontaneously reported adverse reactions related to herbal medicinal products and natural remedies in Sweden. To evaluate the characteristics and frequency of adverse events recorded by the Swedish Medical Products Agency, where herbal medicinal products and natural remedies were suspected as causative agents. Adverse drug reactions reported to the Swedish Medical Product Agency during 2007-15 related to approved herbal medicinal products or natural remedies were included and analysed in the retrospective study. Reports had been assessed for causality when they were lodged and only reports that had been assessed as at least possible were included in the study. In total, 116 reports (concerning 259 adverse reactions) related to herbal medicinal products or natural remedies were found in the Swedish national pharmacovigilance database. The active ingredients most frequently suspected during the study period were black cohosh rhizome (15 reports), purple coneflower herb (14 reports) and a combination of extracts of pollen (13 reports). Adverse reactions related to skin and subcutaneous tissue were the most commonly reported reactions. No previously unknown safety problems have been discovered in the present study. This finding could be explained by a thorough pre-approval assessment of medicinal products and the fact that most herbal preparations in medicinal products have been in clinical use for many years (for traditional herbal medicinal products, the requirements are ≥30 years), i.e. adverse reactions are acknowledged and assessed before approval.

  2. 7 CFR 2902.6 - Providing product information to Federal agencies.

    Science.gov (United States)

    2010-01-01

    ... manufacturers and vendors to provide product, business contacts, and product information for designated items... characteristics, including verification of such characteristics if requested. (b) Advertising, labeling and marketing claims. Manufacturers and vendors are reminded that their advertising, labeling, and other...

  3. 77 FR 20026 - Draft Guidance for Industry: Modified Risk Tobacco Product Applications; Availability; Agency...

    Science.gov (United States)

    2012-04-03

    ... (21 U.S.C. 387k) to the FD&C Act to prohibit the introduction or delivery for introduction into... 911(b)(1) of the FD&C Act). No person may introduce or deliver for introduction into interstate... advertising and labeling; The conditions for using the product; The formulation of the product; Sample product...

  4. 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

  5. Factors to consider in developing individual pharmaceutical product quality risk profiles useful to government procurement agencies.

    Science.gov (United States)

    Xu, Wei; Boehm, Garth; Zheng, Qiang

    2016-01-01

    Governments that procure pharmaceutical products from an Essential Medicine List (EML) bear special responsibility for the quality of these products. In this article we examine the possibility of developing a pharmaceutical product quality risk assessment scheme for use by government procurement officials. We use the Chinese EML as a basis, and US recall data is examined as it is publically available.This is justified as the article is only concerned with inherent product quality risks. After establishing a link between Chinese essential medicines and those available in the US, we examine US recall data to separate product specific recalls. We conclude that, in addition to existing manufacturing based risks, there are two other product specific risks that stand out from all others, degradation and dissolution failure. Methodology for relative product risk for degradation is needed to be developed and further work is required to better understand dissolution failures which largely occur with modified-release solid oral products. We conclude that a product specific quality risk profile would be enhanced by including a risk assessment for degradation for all products, and in the case of solid oral products, dissolution.

  6. The Texts of the Instruments connected with the Agency's Assistance to Argentina in Establishing a Research and Isotope Production Reactor Project

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1965-11-04

    The texts of the Title Transfer Agreement between the Agency and the Governments of Argentina and the United States of America, and of the Project Agreement between the Agency and the Government of Argentina, in connection with the Agency's assistance to that Government in establishing a research and isotope production reactor project, are reproduced in this document for the information of all Members. These Agreements entered into force on 2 December 1964.

  7. The Texts of the Instruments connected with the Agency's Assistance to Argentina in Establishing a Research and Isotope Production Reactor Project

    International Nuclear Information System (INIS)

    1965-01-01

    The texts of the Title Transfer Agreement between the Agency and the Governments of Argentina and the United States of America, and of the Project Agreement between the Agency and the Government of Argentina, in connection with the Agency's assistance to that Government in establishing a research and isotope production reactor project, are reproduced in this document for the information of all Members. These Agreements entered into force on 2 December 1964

  8. O lugar da política na atuação das agências reguladoras independentes brasileiras: reflexões sobre a separação dos poderes no Estado moderno / The Role of Politics in the Brazilian Independent Regulatory Agencies: Reflections on the Separation of Powers in the Modern State

    Directory of Open Access Journals (Sweden)

    Milton Carvalho Gomes

    2017-04-01

    Full Text Available Purpose – The purpose of the proposed article is to investigate the practice of politics in the performance of activities of Brazilian independent regulatory agencies Methodology/approach/design – ... The approach is based on the study of theories about separation of state powers and functions, evaluating the application of these theories in the understanding of the role played by independent regulatory agencies in Brazil Findings – It was concluded that the independence granted by the National Congress to the Brazilian regulatory agencies implied in the expansion of the space of politics in its operation, placing these agencies in a unique position in the context of the separation of powers, changing the traditional institutional arrangement of submission to the executive branch. Practical implications (if applicable –The conclusions permit new reflections on the limits of the influence of the President of the Republic and of the sectoral ministries in the decisions taken by the regulatory agencies, both in the decisions of a technical nature and those of a political nature, allowing the expansion of the debate on the instruments of democratic legitimation of these decisions. Originality/value (optional – The text is original, since there are few in-depth studies in Brazil about the space for politics in the field of independent regulatory agencies, usually understood as purely technical / administrative entities.

  9. A watershed-based environmental and regulatory data analysis system for the forest products industry

    Science.gov (United States)

    John Beebe

    2012-01-01

    A watershed-based data analysis system was created as a tool for forest product companies to better understand potential implications from environmental regulations. Also known as the Receiving Water Database (RWDB), this data system was designed with the purpose of assisting companies that own pulp and paper mills, wood product facilities, and commercial timberlands...

  10. 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.)

  11. Eucalyptus ESTs involved in the production of 9-cis epoxycarotenoid dioxygenase, a regulatory enzyme of abscisic acid production

    Directory of Open Access Journals (Sweden)

    Iraê A. Guerrini

    2005-01-01

    Full Text Available Abscisic acid (ABA regulates stress responses in plants, and genomic tools can help us to understand the mechanisms involved in that process. FAPESP, a Brazilian research foundation, in association with four private forestry companies, has established the FORESTs database (https://forests.esalq.usp.br. A search was carried out in the Eucalyptus expressed sequence tag database to find ESTs involved with 9-cis epoxycarotenoid dioxygenase (NCED, the regulatory enzyme for ABA biosynthesis, using the basic local BLAST alignment tool. We found four clusters (EGEZLV2206B11.g, EGJMWD2252H08.g, EGBFRT3107F10.g, and EGEQFB1200H10.g, which represent similar sequences of the gene that produces NCED. Data showed that the EGBFRT3107F10.g cluster was similar to the maize (Zea mays NCED enzyme, while EGEZLV2206B11.g and EGJMWD2252H08.g clusters were similar to the avocado (Persea americana NCED enzyme. All Eucalyptus clusters were expressed in several tissues, especially in flower buds, where ABA has a special participation during the floral development process.

  12. 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.

  13. BORDERLINE AND CLASSIFICATION IN THE COMMUNITY REGULATORY FRAMEWORK FOR MEDICAL DEVICES – BRIEF REVIEW ON SOME DENTISTRY PRODUCTS.

    Directory of Open Access Journals (Sweden)

    Maya Lyapina

    2015-02-01

    Full Text Available Defining a given product as a medical device and interpretation of the application of the classification rules fall within the competence of the competent authorities of the Member States where the product is on the market. Different interpretations of Community legislation occur, and, can put public health at risk and distort the internal market. Borderline cases are considered to be those cases where it is not clear from the outset whether a given product is a medical device, an in vitro diagnostic medical device, an active implantable medical device or not. Classification cases can be described as those cases where there exists a difficulty in the uniform application of the classification rules as laid down in the Medical Devices Directive (MDD, or where for a given device, depending on interpretation of the rules, different classifications can occur. The aim of the present work is to make a brief review on discussion on classification in the community regulatory framework for medical devices of some dentistry products.

  14. A Two-Component Regulatory System Impacts Extracellular Membrane-Derived Vesicle Production in Group A Streptococcus

    Directory of Open Access Journals (Sweden)

    Ulrike Resch

    2016-11-01

    Full Text Available Export of macromolecules via extracellular membrane-derived vesicles (MVs plays an important role in the biology of Gram-negative bacteria. Gram-positive bacteria have also recently been reported to produce MVs; however, the composition and mechanisms governing vesiculogenesis in Gram-positive bacteria remain undefined. Here, we describe MV production in the Gram-positive human pathogen group A streptococcus (GAS, the etiological agent of necrotizing fasciitis and streptococcal toxic shock syndrome. M1 serotype GAS isolates in culture exhibit MV structures both on the cell wall surface and in the near vicinity of bacterial cells. A comprehensive analysis of MV proteins identified both virulence-associated protein substrates of the general secretory pathway in addition to “anchorless surface proteins.” Characteristic differences in the contents, distributions, and fatty acid compositions of specific lipids between MVs and GAS cell membrane were also observed. Furthermore, deep RNA sequencing of vesicular RNAs revealed that GAS MVs contained differentially abundant RNA species relative to bacterial cellular RNA. MV production by GAS strains varied in a manner dependent on an intact two-component system, CovRS, with MV production negatively regulated by the system. Modulation of MV production through CovRS was found to be independent of both GAS cysteine protease SpeB and capsule biosynthesis. Our data provide an explanation for GAS secretion of macromolecules, including RNAs, lipids, and proteins, and illustrate a regulatory mechanism coordinating this secretory response.

  15. Clinical Development and Commercialization of Advanced Therapy Medicinal Products in the European Union: How Are the Product Pipeline and Regulatory Framework Evolving?

    Science.gov (United States)

    Boráň, Tomáš; Menezes-Ferreira, Margarida; Reischl, Ilona; Celis, Patrick; Ferry, Nicolas; Gänsbacher, Bernd; Krafft, Hartmut; Lipucci di Paola, Michele; Sladowski, Dariusz; Salmikangas, Paula

    2017-09-01

    The research and development of advanced therapy medicinal products (ATMPs) has been active in Europe and worldwide during recent years. Yet, the number of licensed products remains low. The main expected legal change in the near future in the European Union (EU) concerns the regulation on clinical trials (536/2014), which will come into force in 2018. With this new framework, a more harmonized and swift process for approval of clinical trials is anticipated, which is expected to support the entry of new innovations into the EU market. A survey on ATMPs in clinical trials during 2010-2015 in the EU was conducted in order to study the trends of ATMP development since the earlier survey published in 2012. According to the results, the number of clinical trials using ATMPs is slowly increasing in the EU. Yet, the focus is still in early development, and the projects are mainly carried out by small and medium-sized enterprises, academia, and hospitals. Oncology is the main area of clinical development. Yet, the balance between cell-based products and gene therapy medicinal products in this area may be changing in the future due to the new T-cell technologies. Many limitations and challenges are identified for ATMP development, requiring proportionate regulatory requirements. On the other hand, for such a novel field, the developers should be active in considering possible constraints and actively engage with authorities to look for solutions. This article provides up to-date information on forthcoming regulatory improvements and discusses the main challenges hampering the commercialization of ATMPs in the EU.

  16. Made in China: Policy Analysis and Prescriptions to Improve China's Consumer Product Safety Regulatory Regime

    National Research Council Canada - National Science Library

    McMullin, III, James A

    2008-01-01

    China's central government's response to the current challenge of consumer product safety in the food and drug arena could be a determining factor in its ability to sustain robust economic growth over the next decade...

  17. [Translational/regulatory science researches of NIHS for regenerative medicine and cellular therapy products].

    Science.gov (United States)

    Sato, Yoji

    2014-01-01

    In 2013, the Japanese Diet passed the Regenerative Medicine Promotion Act and the revisions to the Pharmaceutical Affairs Act, which was also renamed as the Therapeutic Products Act (TPA). One of the aims of the new/revised Acts is to promote the development and translation of and access to regenerative/cellular therapies. In the TPA, a product derived from processing cells is categorized as a subgroup of "regenerative medicine, cellular therapy and gene therapy products" (RCGPs), products distinct from pharmaceuticals and medical devices, allowing RCGPs to obtain a conditional and time- limited marketing authorization much earlier than that under the conventional system. To foster not only RCGPs, but also innovative pharmaceuticals and medical devices, the Ministry of Health, Labour and Welfare recently launched Translational Research Program for Innovative Pharmaceuticals, Medical Devices and RCGPs. This mini-review introduces contributions of the National Institute of Health Sciences (NIHS) to research projects on RCGPs in the Program.

  18. An Analysis of Malaysia’s Regulatory Framework and Challenges in the Structured Product Market

    OpenAIRE

    Ling, Eu Meng

    2008-01-01

    Structured products are becoming increasingly popular and important to the development of Malaysia’s capital market and had experience impressive growth over the last few years after it was first introduced to the Malaysian market in 2004. Like any industry in its early stage, issues and challenges are expected but for structured products, such challenges require more attention due to the complexity inherent in these instruments. This study uses a qualitative research approach in an attempt t...

  19. 77 FR 35110 - Agency Information Collection Activity Under OMB Review: Production Plan Reports

    Science.gov (United States)

    2012-06-12

    ... methods: Federal eRulemaking Portal: http://www.regulations.gov . Follow the online instructions for... products, in order to examine how manufacturers anticipate tying technology introduction to product design... for light-duty fuel economy standards. These standards may be issued for a one to five year time frame...

  20. 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

  1. 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

  2. As agências reguladoras independentes e o Tribunal de Contas da União: conflito de jurisdições? The independent regulatory agencies and the Federal Court of Accounts: a jurisdictional conflict?

    Directory of Open Access Journals (Sweden)

    Eduardo Granha Magalhães Gomes

    2006-08-01

    Full Text Available Este artigo analisa a emergência, no Brasil, de agências reguladoras independentes (ARIs e suas especificidades quanto ao desenho institucional; analisa ainda a evolução recente da atuação do Tribunal de Contas da União (TCU no contexto da nova gestão pública. No desenho das ARIs têm destaque os mecanismos que lhes conferem independência política, dada a natureza de suas atribuições e competências. Por outro lado, o TCU vem ampliando seu campo de atuação, passando a avaliar não mais apenas os aspectos formais da legalidade de procedimentos, mas também o desempenho e resultados alcançados por órgãos e entidades públicas. O TCU passa a atuar no acompanhamento e avaliação do desempenho das agências. O artigo analisa a interface entre independência e controle, discutindo possíveis conflitos institucionais entre as agências reguladoras e o TCU.This article analyzes the emergence of the independent regulatory agencies (IRAs in Brazil and their specificities as to their institutional design. It also discusses the recent developments in the Federal Court of Accounts' actions within the new public management context. IRAs were designed with emphasis on the features that give them political independence, considering the nature of their attributions and capabilities. On the other hand, the Federal Court of Accounts (FCA has broadened its area of activities, assessing not only the formal aspects of the legality of procedures, but also the performance and the results of organisms and public institutions. The FCA is tracking and assessing the agencies' performance. The article analyzes the interface between independence and control, discussing possible institutional conflicts between regulatory agencies and the FCA.

  3. 41 CFR 102-74.75 - May Federal agencies sell tobacco products in vending machines in Government-owned and leased space?

    Science.gov (United States)

    2010-07-01

    ... sell tobacco products in vending machines in Government-owned and leased space? 102-74.75 Section 102... Services § 102-74.75 May Federal agencies sell tobacco products in vending machines in Government-owned and leased space? No. Section 636 of Public Law 104-52 prohibits the sale of tobacco products in vending...

  4. 75 FR 79049 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-12-17

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2008-0427] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 3.12...

  5. 75 FR 45173 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-08-02

    ... ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are... NUCLEAR REGULATORY COMMISSION [NRC-2008-0638] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.151...

  6. 76 FR 18262 - Notice of issuance of Regulatory Guide

    Science.gov (United States)

    2011-04-01

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0277] Notice of issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.44...

  7. 76 FR 14107 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2011-03-15

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0276] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.43...

  8. 76 FR 14108 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2011-03-15

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0275] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.50...

  9. Regulatory focus, self-efficacy and outcome expectations as drivers of motivation to consume healthy food products.

    Science.gov (United States)

    Tudoran, Ana Alina; Scholderer, Joachim; Brunsø, Karen

    2012-10-01

    In this paper we apply the principle of Regulatory Focus Theory to investigate the interaction between self-efficacy and outcome expectations on individuals' intentions to adopt health behaviors. The participants, 959 individuals (Survey 1) and 2400 individuals (Survey 2), reported self-efficacy beliefs and outcome expectations with regard to the consumption of omega-3 supplements and omega-3-enriched food products. We found that the relationship prevention outcome expectations-intention was significantly attenuated at low levels of self-efficacy and strengthened at high levels of self-efficacy, respectively; whereas, the relationship promotion outcome expectations-intention was unaffected by the perceived levels of self-efficacy. The implications suggest that consumers' motivation to adopt healthy food products, such as omega-3 supplements and omega-3 enriched products, should be encouraged by stimulating promotion outcome expectations. However, when a prevention frame is used, the individuals' motivation should be significantly enhanced by self-efficacy beliefs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Regulatory impact analysis of national emissions standards for hazardous air pollutants for by-product coke oven charging, door leaks, and topside leaks. Draft report

    International Nuclear Information System (INIS)

    1992-11-01

    Under the authority of the 1990 Clean Air Act Amendments, a Natioal Emissions Standard for Hazardous Air Pollutants is proposed to control emissions from By-product Coke Oven Charging, door leaks, and topside leaks. Because the EPA considers the regulation for By-product Coke Oven batteries to be a major rule, the attached Regulatory Impact Analysis was prepared to fulfill the requirements of E012291. The document reviews the need for regulation, control techniques, regulatory options, costs of control, economic impacts, benefits of the regulation, and compares benefits and costs associated with the regulation

  11. Predictive modelling of migration from packaging materials into food products for regulatory purposes

    NARCIS (Netherlands)

    Helmroth, E.; Rijk, R.; Dekker, M.; Jongen, W.

    2002-01-01

    Migration of low-molecular weight compounds is one of the most important problems of packaging plastics and other plastics intended to come into contact with food products. Since migration experiments are time consuming and expensive, predictive modelling has been introduced as a promising

  12. 17 CFR 240.6h-1 - Settlement and regulatory halt requirements for security futures products.

    Science.gov (United States)

    2010-04-01

    ... investors and the public interest, taking into account such factors as fairness to buyers and sellers of the affected security futures product, the maintenance of a fair and orderly market in such security futures... with the protection of investors. An exemption granted pursuant to this paragraph shall not operate as...

  13. 77 FR 8082 - Regulatory Flexibility Agenda

    Science.gov (United States)

    2012-02-13

    ... Required: Yes. Agency Contact: Alicia Goldin, Division of Trading and Markets, Securities and Exchange.../01/11 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Alicia Goldin, Division of... Withdrawn 10/01/11 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Alicia Goldin, Division of...

  14. Results of the International Energy Agency Round Robin on Fast Pyrolysis Bio-oil Production

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, Douglas C.; Meier, Dietrich; Oasmaa, Anja; van de Beld, Bert; Bridgwater, Anthony V.; Marklund, Magnus

    2017-04-06

    An international round robin study of the production of fast pyrolysis bio-oil was undertaken. Fifteen institutions in six countries contributed. Three biomass samples were distributed to the laboratories for processing in fast pyrolysis reactors. Samples of the bio-oil produced were transported to a central analytical laboratory for analysis. The round robin was focused on validating the pyrolysis community understanding of production of fast pyrolysis bio-oil by providing a common feedstock for bio-oil preparation. The round robin included: •distribution of 3 feedstock samples from a common source to each participating laboratory; •preparation of fast pyrolysis bio-oil in each laboratory with the 3 feedstocks provided; •return of the 3 bio-oil products (minimum 500 ml) with operational description to a central analytical laboratory for bio-oil property determination. The analyses of interest were: density, viscosity, dissolved water, filterable solids, CHN, S, trace element analysis, ash, total acid number, pyrolytic lignin, and accelerated aging of bio-oil. In addition, an effort was made to compare the bio-oil components to the products of analytical pyrolysis through GC/MS analysis. The results showed that clear differences can occur in fast pyrolysis bio-oil properties by applying different reactor technologies or configurations. The comparison to analytical pyrolysis method suggested that Py-GC/MS could serve as a rapid screening method for bio-oil composition when produced in fluid-bed reactors. Furthermore, hot vapor filtration generally resulted in the most favorable bio-oil product, with respect to water, solids, viscosity, and total acid number. These results can be helpful in understanding the variation in bio-oil production methods and their effects on bio-oil product composition.

  15. Development of regulatory criteria applicable to control of radiation exposures to the population from products containing radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, L R; Western, F [U.S. Atomic Energy Commission, Germantown, MD (United States)

    1969-07-01

    Under the Atomic Energy Act of 1954 as amended, the Atomic Energy Commission is responsible for regulating the possession, use and transfer of byproduct, source and special nuclear materials in accordance with safety standards established by rule of the Commission to protect health and minimize danger to life and property. This paper describes some of the basic considerations in establishing safety criteria and regulations for authorizing the transfer and use of byproduct material (radioisotopes) in products for distribution to the general public. It discusses problems encountered in extending the broad guidance provided by the Federal Radiation Council (FRC) and by the International Commission of Radiological Protection and the National Council on Radiation Protection and Measurements (ICRP-NCRP), which is limited to total exposures of individuals and population groups to radiation from many sources, to appropriate controls on radioactivity in an individual consumer product which represents only one source of population exposures. The paper also discusses possible approaches to accomplishing the regulatory objectives of providing reasonable assurance that (1) the contribution of an individual product to total exposures that might be permitted under FRC and ICRP-NCRP guidance should not be disproportionate to the benefits to be derived, and (2) appropriate efforts are made to limit exposures to the population from individual classes of sources of exposure as far as practicable. Existing criteria and regulations pertaining to the control of radiation exposure to the population from products into which radioactive material is purposely introduced are described, and additional considerations which must be taken into account for the development of further criteria and regulations which are applicable to the possible wide-scale distribution of products containing radioactive material as a result of the Plowshare Programs are explored. (author)

  16. Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment.

    Science.gov (United States)

    Molins, B; Mesquida, M; Lee, R W J; Llorenç, V; Pelegrín, L; Adán, A

    2015-03-01

    The aim of this study was to quantify the proportion of regulatory T cells (Treg ) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non-infectious uveitis, and to evaluate the effect of in-vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non-infectious uveitis and 18 age-matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)(+) Treg cells and intracellular tumour necrosis factor (TNF)-α expression in CD4(+) T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti-CD3/anti-CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF-α, interleukin (IL)-10, IL-17 and interferon (IFN)-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF-α and lower amounts of IL-10. Dexamethasone treatment in vitro significantly reduced FoxP3(+) Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF-α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL-17 and IFN-γ production in PBMCs and dexamethasone up-regulated IL-10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF-α and less IL-10 than healthy subjects, and this is independent of FoxP3(+) Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3(+) Treg cells. © 2014 British Society for Immunology.

  17. Development of regulatory criteria applicable to control of radiation exposures to the population from products containing radioactive material

    International Nuclear Information System (INIS)

    Rogers, L.R.; Western, F.

    1969-01-01

    Under the Atomic Energy Act of 1954 as amended, the Atomic Energy Commission is responsible for regulating the possession, use and transfer of byproduct, source and special nuclear materials in accordance with safety standards established by rule of the Commission to protect health and minimize danger to life and property. This paper describes some of the basic considerations in establishing safety criteria and regulations for authorizing the transfer and use of byproduct material (radioisotopes) in products for distribution to the general public. It discusses problems encountered in extending the broad guidance provided by the Federal Radiation Council (FRC) and by the International Commission of Radiological Protection and the National Council on Radiation Protection and Measurements (ICRP-NCRP), which is limited to total exposures of individuals and population groups to radiation from many sources, to appropriate controls on radioactivity in an individual consumer product which represents only one source of population exposures. The paper also discusses possible approaches to accomplishing the regulatory objectives of providing reasonable assurance that (1) the contribution of an individual product to total exposures that might be permitted under FRC and ICRP-NCRP guidance should not be disproportionate to the benefits to be derived, and (2) appropriate efforts are made to limit exposures to the population from individual classes of sources of exposure as far as practicable. Existing criteria and regulations pertaining to the control of radiation exposure to the population from products into which radioactive material is purposely introduced are described, and additional considerations which must be taken into account for the development of further criteria and regulations which are applicable to the possible wide-scale distribution of products containing radioactive material as a result of the Plowshare Programs are explored. (author)

  18. 78 FR 40203 - New Postal Product

    Science.gov (United States)

    2013-07-03

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to add a new product to the competitive product list. This document... Rate Boxes--Non-Published Rates (PMI RRB-NPR) to the competitive product list.\\1\\ It provides a related...

  19. 78 FR 43245 - New Postal Product

    Science.gov (United States)

    2013-07-19

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing concerning the addition of Priority Mail Contract 61 to the competitive product... the competitive product list.\\1\\ It asserts that Priority Mail Contract 61 is a competitive product...

  20. 75 FR 45174 - New Postal Product

    Science.gov (United States)

    2010-08-02

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... competitive product list. The Postal Service has also filed a related contract. This notice addresses... product list within the Mail Classification Schedule (MCS).\\1\\ This product grouping would create a niche...

  1. 77 FR 61307 - New Postal Product

    Science.gov (United States)

    2012-10-09

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... dominant product list to the competitive product list as ``Lightweight Parcel Select,'' a subcategory of... Granting Request to Transfer Commercial Standard Mail Parcels to the Competitive Product List, March 2...

  2. 77 FR 1957 - New Postal Product

    Science.gov (United States)

    2012-01-12

    ... Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently filed Postal Service request to add Global Plus 2C Contracts to the competitive product..., consisting of two Global Plus 2C agreements, to the competitive products list.\\1\\ The new product covers...

  3. 78 FR 39783 - New Postal Product

    Science.gov (United States)

    2013-07-02

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to add a new product to the competitive product list. This document... and associated supporting information to add Priority Mail Contract 60 to the competitive product list...

  4. 75 FR 22868 - Withdrawal of Regulatory Guide

    Science.gov (United States)

    2010-04-30

    ...'s public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are also available for inspection at the NRC's... NUCLEAR REGULATORY COMMISSION [NRC-2010-0167] Withdrawal of Regulatory Guide AGENCY: Nuclear...

  5. DEFENSE PRODUCTION ACT: Agencies Lack Policies and Guidance for Use of Key Authorities

    Science.gov (United States)

    2008-06-01

    and its allies $67.10 Titanium Metal Matrix Composites for Aircraft Supplies material properties that enable aircraft designers to engineer...Flexible Aerogel Material Supplier Initiative Provides nanoporous solids with up to 99 percent open porosity often called “frozen smoke” $14.62...lightweight explosive detector device $1.06 Continuous Filament Boron Fiber Production Provides boron fiber needed for aircraft structure reinforcement and

  6. US regulatory system for genetically modified [genetically modified organism (GMO), rDNA or transgenic] crop cultivars.

    Science.gov (United States)

    McHughen, Alan; Smyth, Stuart

    2008-01-01

    This paper reviews the history of the federal regulatory oversight of plant agricultural biotechnology in the USA, focusing on the scientific and political forces moulding the continually evolving regulatory structure in place today. Unlike most other jurisdictions, the USA decided to adapt pre-existing legislation to encompass products of biotechnology. In so doing, it established an overarching committee (Office of Science and Technology Policy) to study and distribute various regulatory responsibilities amongst relevant agencies: the Food and Drug Administration, Environmental Protection Agency and US Department of Agriculture. This paper reviews the history and procedures of each agency in the execution of its regulatory duties and investigates the advantages and disadvantages of the US regulatory strategy.

  7. 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)

  8. Transgene mobilization and regulatory uncertainty for non-GE fruit products of transgenic rootstocks.

    Science.gov (United States)

    Haroldsen, Victor M; Chi-Ham, Cecilia L; Bennett, Alan B

    2012-10-31

    Genetically engineered (GE) rootstocks may offer some advantages for biotechnology applications especially in woody perennial crops such as grape or walnut. Transgrafting combines horticultural grafting practices with modern GE methods for crop improvement. Here, a non-GE conventional scion (upper stem portion) is grafted onto a transgenic GE rootstock. Thus, the scion does not contain the genetic modification present in the rootstock genome. We examined transgene presence in walnut and tomato GE rootstocks and non-GE fruit-bearing scions. Mobilization of transgene DNA, protein, and mRNA across the graft was not detected. Though transgenic siRNA mobilization was not observed in grafted tomatoes or walnut scions, transgenic siRNA signal was detected in walnut kernels. Prospective benefits from transgrafted plants include minimized risk of GE pollen flow (Lev-Yadun and Sederoff, 2001), possible use of more than one scion per approved GE rootstock which could help curb the estimated US$136 million (CropLife International, 2011) cost to bring a GE crop to international markets, as well as potential for improved consumer and market acceptance since the consumable product is not itself GE. Thus, transgrafting provides an alternative option for agricultural industries wishing to expand their biotechnology portfolio. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Federal Energy Regulatory Commission (FERC) Regions

    Data.gov (United States)

    Department of Homeland Security — Federal Energy Regulatory Commission (FERC) Regions. FERC is an independent agency that regulates the interstate transmission of electricity, natural gas, and oil....

  10. Film as teacher education genre: Developing student agency in the production of #Taximaths – How children make their world mathematical

    Directory of Open Access Journals (Sweden)

    Lara Ragpot

    2014-12-01

    Full Text Available The article reports on the process of producing a film for students in a university course. The purpose of the production was to make local film material that could assist students in their learning of developmental cognitive psychology theory in general, but specifically also the mathematical cognition of children. Although the students in the production team set out as actors and technical helpers, they gradually appropriated their acting roles and the plot of the story to the extent that they learned the theory that the film was portraying. Not only did they show interest in the psychology texts and the story, but they also developed agency – they became the owners of the film. The argument of this paper is that a multimodal foundation in teacher education can give students multiple semiotic entry points, but also, if given the opportunity to make a dramatic film, they can learn the content of mathematical cognition while learning film production. The article argues that contemporary teacher education programmes are by their very nature briefed to be multimodal, because teachers’ work in schools in the 21st century requires more than language text and oral, in-person communication.

  11. Agency perspectives on food safety for the products of animal biotechnology.

    Science.gov (United States)

    Howard, H J; Jones, K M; Rudenko, L

    2012-08-01

    Animal biotechnology represents one subset of tools among a larger set of technologies for potential use to meet increasing world demands for food. Assisted reproductive technologies (ART) such as artificial insemination and embryo transfer continue to make positive contributions in food animal production. The US Food and Drug Administration (FDA) performed a comprehensive risk assessment to identify potential food consumption or animal health risks associated with animal cloning, an emerging ART. At that time, FDA concluded that animal cloning posed no unique risks either to animal health or to food consumption, and food from animal clones and their sexually reproduced offspring required no additional federal regulation beyond that applicable to conventionally bred animals of the species examined. At this time, no new information has arisen that would necessitate a change in FDA's conclusions on food from animal clones or their sexually reproduced offspring. Use of recombinant DNA technologies to produce genetically engineered (GE) animals represents another emerging technology with potential to impact food animal production. In its regulation of GE animals, FDA follows a cumulative, risk-based approach to address scientific questions related to the GE animals. FDA evaluates data and information on the safety, effectiveness and stability of the GE event. FDA carries out its review at several levels (e.g. molecular biology, animal safety, food safety, environmental safety and claim validation). GE animal sponsors provide data to address risk questions for each level. This manuscript discusses FDA's role in evaluation of animal cloning and GE animals. © 2012 Blackwell Verlag GmbH.

  12. Factors associated with regulatory action involving investigation of illnesses associated with Shiga toxin-producing Escherichia coli in products regulated by the Food Safety and Inspection Service.

    Science.gov (United States)

    Green, Alice L; Seys, Scott; Douris, Aphrodite; Levine, Jeoff; Robertson, Kis

    2014-07-01

    We described characteristics of the Escherichia coli O157 and Escherichia coli non-O157 illness investigations conducted by the United States Department of Agriculture's Food Safety and Inspection Service (FSIS) during the 5-year period from 2006 through 2010. We created a multivariable logistic regression model to determine characteristics of these investigations that were associated with FSIS regulatory action, which was defined as having occurred if a product recall occurred or if FSIS personnel performed an environmental health assessment (Food Safety Assessment) at the implicated establishment. During this period, FSIS took regulatory action in 38 of 88 (43%) investigations. Illness investigations in which FoodNet states were involved were more likely to result in regulatory action. Illness investigations in which state and local traceback, or FSIS traceback occurred were more likely to result in regulatory action. Reasons for lack of action included evidence of cross-contamination after the product left a regulated establishment, delayed notification, lack of epidemiological information, and insufficient product information.

  13. Regulatory issues for Waste Isolation Pilot Plant long-term compliance with U.S. Environmental Protection Agency 40 CFR 191B and 268

    International Nuclear Information System (INIS)

    Anderson, D.R.; Marietta, M.G.; Higgins, P.J. Jr.

    1993-10-01

    Before disposing of transuranic radioactive waste at the Waste Isolation Pilot Plant (WIPP), the United States Department of Energy (DOE) must evaluate compliance with long-term regulations of the United States Environmental Protection Agency (EPA), specifically the Environmental Standards for the Management and Disposal of Spent Nuclear Fuel, High-Level and Transuranic Radioactive Wastes (40 CFR 191), and the Land Disposal Restrictions (40 CFR 268) of the Hazardous and Solid Waste Amendments to the Resource Conservation and Recovery Act (RCRA). Sandia National Laboratories (SNL) is conducting iterative performance assessments (PAs) of the WIPP for the DOE to provide interim guidance while preparing for final compliance evaluations. This paper provides background information on the regulations, describes the SNL WIPP PA Departments approach to developing a defensible technical basis for consistent compliance evaluations, and summarizes the major observations and conclusions drawn from the 1991 and 1992 PAs

  14. Importance of the awareness, training exchange of information and co-operation between regulatory authorities and customs, police and other law enforcement agencies

    International Nuclear Information System (INIS)

    Shakshooki, S.K.; Al-Ahaimer, R.O.

    1998-01-01

    Fast developments in science and technology are a great accomplishment in this century. These facilities have been utilized by criminals and deviants by identified way. Industrial developed countries have their own means to improve and to modify technology and scientific facilities to cope up with any new existing problems, such as the problem of illegal trading of nuclear materials. Facilities for exchange of information among industrial countries also play an important role to prevent any dangerous phenomena may exist. In contrast most developing countries lack the means of up-to-date follow up quick and continuous scientific and technological developments. However they have qualified personnel to follow up quickly and to prevent drug and narcotics smuggling. Recently we have heard about a dangerous phenomena, the illegal trading of nuclear materials, which derive attention internationally. The developed countries can cope easily with it. However, in developing countries, their lack of up to date facilities can cause a grate damage to their nations. Libyan Arab Jamahiriya is always willing to co-operate internationally to prevent any new dangerous phenomena. We think it is a time for conformation on international official agreement regarding this phenomena. Exchange of information between different countries through an international agency is important for prohibiting the illegal nuclear materials trading. Also to help in creation of a temporally scientific committee to provide different countries of the world the available information in this area and to co-operate specially with police, custom and law enforcement agencies of each nation providing an international legislation for dealing with such phenomena is a priority. Assistance for the arrangement of training through IAEA is of great importance. (author)

  15. The text of the instruments connected with the Agency's assistance to Argentina in establishing a research and isotope production reactor project

    International Nuclear Information System (INIS)

    1995-01-01

    The Agreement between the Republic of Argentina, the Federative Republic of Brazil, the Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials and the International Atomic Energy Agency for the Application of Safeguards came into force on 4 March 1994. As a result of the coming into force of the aforesaid Agreement for Argentina, the application of safeguards under the Project Agreement of 2 December 1964 between Argentina and the IAEA in connection with the Agency's assistance to Argentina in establishing a research and isotope production reactor project has been suspended

  16. 75 FR 21871 - Spring 2010 Regulatory Agenda

    Science.gov (United States)

    2010-04-26

    ... Review 10/00/10 Regulatory Flexibility Analysis Required: No Agency Contact: Tad Wysor, Environmental...: wysor.tad@epamail.epa.gov Tom Eagles, Environmental Protection Agency, Air and Radiation, 6103A...

  17. H.R. 5448: a bill to amend the Atomic Energy Act of 1954, as amended, to reorganize the functions of the Nuclear Regulatory Commission by abolishing the Commission and in its place establishing the Nuclear Regulation and Safety Agency. Introduced in the House of Representatives, Ninety-Ninth Congress, Second Session, August 15, 1986

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    The Omnibus Nuclear Safety Act of 1986 amends the Atomic Energy Act of 1954 by replacing the Nuclear Regulatory Commission with a new entity, the Nuclear Regulation and Safety Agency. The purposes are to promote an energy policy that is better coordinated and more consistent with the protection of public health and safety. The new agency would also expedite licensing for construction and operation of nuclear power plants by using pre-approved standardized designs and sites

  18. 78 FR 1634 - Regulatory Agenda

    Science.gov (United States)

    2013-01-08

    ... amendments include updates to organizational information, use of the term ``disability'' in lieu of the term.../00/13 Regulatory Flexibility Analysis Required: No. Agency Contact: Robert W. Cosgrove, External...

  19. 78 FR 44329 - Regulatory Agenda

    Science.gov (United States)

    2013-07-23

    ... amendments include updates to organizational information, use of the term ``disability'' in lieu of the term.../00/13 Regulatory Flexibility Analysis Required: No. Agency Contact: Robert W. Cosgrove, External...

  20. Current concepts on integrative safety assessment of active substances of botanical, mineral or chemical origin in homeopathic medicinal products within the European regulatory framework.

    Science.gov (United States)

    Buchholzer, Marie-Luise; Werner, Christine; Knoess, Werner

    2014-03-01

    For active substances of botanical, mineral or chemical origin processed in homeopathic medicinal products for human use, the adequate safety principles as with other human medicinal products are applied in line with the European regulatory framework. In homeopathy, nonclinical safety assessment is facing a particular challenge because of a multitude and diversity of source materials used and due to rarely available toxicological data. Thus, current concepts applied by the national regulatory authority in Germany (BfArM) on integrative safety assessment of raw materials used in homeopathic medicinal products involve several evaluation approaches like the use of the Lowest Human Recommended Dose (LHRD), toxicological limit values, Threshold of Toxicological Concern (TTC), data from food regulation or the consideration of unavoidable environmental or dietary background exposure. This publication is intended to further develop and clarify the practical use of these assessment routes by exemplary application on selected homeopathic preparations. In conclusion, the different approaches are considered a very useful scientific and simultaneously pragmatic procedure in differentiated risk assessment of homeopathic medicinal products. Overall, this paper aims to increase the visibility of the safety issues in homeopathy and to stimulate scientific discussion of worldwide existing regulatory concepts on homeopathic medicinal products. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. 77 FR 64567 - Product List Change

    Science.gov (United States)

    2012-10-22

    ... Delivery service from the competitive product list due to low customer demand.\\2\\ It states that there are... POSTAL REGULATORY COMMISSION [Docket No. MC2013-3; Order No. 1503] Product List Change AGENCY... product list. This notice provides public notice of the Postal Service's filing, invites public comment...

  2. 77 FR 67840 - New Postal Product

    Science.gov (United States)

    2012-11-14

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent... competitive product list. This notice informs the public of the filing, invites public comment, and takes... to add First-Class Package Service Contract 26 to the competitive product list.\\1\\ The Postal Service...

  3. 75 FR 44819 - New Postal Product

    Science.gov (United States)

    2010-07-29

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service filing to add Priority Mail Contract 27 to the competitive product list. The... to add Priority Mail Contract 27 to the competitive product list.\\1\\ The Postal Service asserts that...

  4. 75 FR 11452 - New Postal Product

    Science.gov (United States)

    2010-03-11

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Final rule. SUMMARY: The Commission is adding special postal services to the product lists. This action is consistent with changes in a postal reform law. Republication of the product lists is also consistent with a statutory provision. The Commission...

  5. 77 FR 58185 - New Postal Product

    Science.gov (United States)

    2012-09-19

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2012-56; Order No. 1464] New Postal Product AGENCY... Service request to add a Global Expedited Package Services contract to the competitive product list. This... contracts are small- or medium-size businesses that mail products directly to foreign destinations using...

  6. 77 FR 58422 - New Postal Product

    Science.gov (United States)

    2012-09-20

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to add Priority Mail Contract 43 to the competitive product list... request and associated supporting information to add Priority Mail Contract 43 to the competitive product...

  7. 75 FR 45176 - New Postal Product

    Science.gov (United States)

    2010-08-02

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to add Priority Mail Contract 25 to the competitive product list. The... associated supporting information to add Priority Mail Contract 25 to the competitive product list.\\1\\ The...

  8. 76 FR 80412 - New Postal Product

    Science.gov (United States)

    2011-12-23

    ... POSTAL REGULATORY COMMISSION Docket No. CP2012-4; Order No. 1057] New Postal Product AGENCY... Agreement within the Inbound Competitive Multi-Service Agreement with a Foreign Postal Operators 1 product... explaining why, after the change, competitive products in total will be in compliance with 39 U.S.C. 3633(a...

  9. 77 FR 60727 - New Postal Product

    Science.gov (United States)

    2012-10-04

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... product list. This notice addresses procedural steps associated with this filing. DATES: Comments are due... competitive product list.\\1\\ The Postal Service asserts that First- Class Package Service Contract 20 is a...

  10. 76 FR 67496 - New Postal Product

    Science.gov (United States)

    2011-11-01

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2012-1; Order No. 919] New Postal Product AGENCY... to the Inbound Competitive Multi-Service Agreements with Foreign Postal Operators 1 product. \\1... Operators 1 to the Competitive Product List and Approving Included Agreement, September 29, 2010 (Order No...

  11. 75 FR 45175 - New Postal Product

    Science.gov (United States)

    2010-08-02

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... to the competitive product list. This notice addresses procedural steps associated with the filing... that Order No. 86, which established GEPS 1 as a product, also authorized functionally equivalent...

  12. 78 FR 4478 - New Postal Product

    Science.gov (United States)

    2013-01-22

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2013-42; Order No. 1623] New Postal Product AGENCY... within the Global Plus 2C product on the grounds of functional equivalence to previously approved.... Id. at 1. Background. The Commission added Global Plus 2 to the competitive product list, based on...

  13. 78 FR 37851 - New Postal Product

    Science.gov (United States)

    2013-06-24

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2013-68; Order No. 1750] New Postal Product AGENCY... filing concerning the addition of Global Expedited Package Services 3 Contract to the competitive product... GEPS 3 product. Notice at 2. \\1\\ Notice of United States Postal Service of Filing a Functionally...

  14. 78 FR 26405 - New Postal Product

    Science.gov (United States)

    2013-05-06

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing concerning the addition of Priority Mail Contract 58 to the competitive product... 58 to the competitive product list.\\1\\ It asserts that Priority Mail Contract 58 is a competitive...

  15. 78 FR 26404 - New Competitive Product

    Science.gov (United States)

    2013-05-06

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent... product list. This notice informs the public of the filing, invites public comment, and takes other... the competitive product list.\\1\\ The Postal Service asserts that Parcel Return Service Contract 4 is a...

  16. 78 FR 29784 - New Postal Product

    Science.gov (United States)

    2013-05-21

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2013-62; Order No. 1716] New Postal Product AGENCY... filing concerning the addition of Global Expedited Package Services 3 Contract to the competitive product... GEPS 3 product on grounds of functional equivalence to a previously approved baseline agreement. Id. at...

  17. 77 FR 60726 - New Postal Product

    Science.gov (United States)

    2012-10-04

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... product list. This notice addresses procedural steps associated with this filing. DATES: Comments are due... 19 to the competitive product list.\\1\\ The Postal Service asserts that First- Class Package Service...

  18. 78 FR 963 - New Postal Product

    Science.gov (United States)

    2013-01-07

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent... 4 to the competitive product list. This notice informs the public of the filing, invites public... product list.\\1\\ The Postal Service states that the addition is necessary due to changes in the non...

  19. 77 FR 60725 - New Postal Product

    Science.gov (United States)

    2012-10-04

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... product list. This notice addresses procedural steps associated with this filing. DATES: Comments are due... competitive product list.\\1\\ The Postal Service asserts that First- Class Package Service Contract 16 is a...

  20. 75 FR 7296 - New Postal Product

    Science.gov (United States)

    2010-02-18

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2010-23; Order No. 405] New Postal Product AGENCY... Service request to add a Global Expedited Package Services 2 contract to the Competitive Product List... established GEPS 1 as a product, also authorized functionally equivalent agreements to be included within the...

  1. 77 FR 24996 - New Postal Product

    Science.gov (United States)

    2012-04-26

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... product list. This notice addresses procedural steps associated with the filing. DATES: Comments are due... supporting information to add First-Class Package Service Contract 1 to the Competitive Product List.\\1\\ The...

  2. 78 FR 13714 - New Postal Product

    Science.gov (United States)

    2013-02-28

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing concerning the addition of Priority Mail Contract 55 to the competitive product... 55 to the competitive product list.\\1\\ It asserts that Priority Mail Contract 55 is a competitive...

  3. 78 FR 20697 - New Competitive Product

    Science.gov (United States)

    2013-04-05

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing concerning an addition to the competitive product list. This notice informs the... request and associated supporting information to add Priority Mail Contract 57 to the competitive product...

  4. 75 FR 4593 - New Postal Product

    Science.gov (United States)

    2010-01-28

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2010-20; Order No. 397] New Postal Product AGENCY... Service request to add GEPS 2 (CP2009-50) to the Competitive Product List. The Postal Service has also... Global Expedited Package Services 2 to the Competitive Product List, August 28, 2009 (Order No. 290). \\4...

  5. 77 FR 60729 - New Postal Product

    Science.gov (United States)

    2012-10-04

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... product list. This notice addresses procedural steps associated with this filing. DATES: Comments are due... competitive product list.\\1\\ The Postal Service asserts that First- Class Package Service Contract 17 is a...

  6. 78 FR 70084 - New Postal Product

    Science.gov (United States)

    2013-11-22

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing concerning the addition of Priority Mail Contract 65 to the competitive product... information to add Priority Mail Contract 65 to the competitive product list.\\1\\ It asserts that Priority Mail...

  7. 78 FR 76332 - New Postal Product

    Science.gov (United States)

    2013-12-17

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing recent Postal Service filings requesting the addition of Priority Mail Contract 71 to the competitive product... Contract 71 to the competitive product list.\\1\\ The Postal Service asserts [[Page 76333

  8. 78 FR 79022 - New Postal Product

    Science.gov (United States)

    2013-12-27

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent... product list. This notice informs the public of the filing, invites public comment, and takes other... Mail Express Contract 16 to the competitive product list.\\1\\ The Postal Service asserts that Priority...

  9. 78 FR 65016 - New Postal Product

    Science.gov (United States)

    2013-10-30

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing recent Postal Service filings requesting the addition of Priority Mail Contract 66 to the competitive product... Contract 66 to the competitive product list.\\1\\ It is the successor agreement to the contract approved in...

  10. 78 FR 20360 - New Competitive Product

    Science.gov (United States)

    2013-04-04

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing concerning the addition of Priority Mail Contract 56 to the competitive product... 56 to the competitive product list.\\1\\ The Postal Service asserts that Priority Mail Contract 56 is a...

  11. 77 FR 4376 - New Postal Product

    Science.gov (United States)

    2012-01-27

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to add Priority Mail Contract 38 to the competitive product list... 38 to the competitive product list.\\1\\ Priority mail contracts enable the Postal Service to provide...

  12. 78 FR 13713 - New Postal Product

    Science.gov (United States)

    2013-02-28

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing concerning the addition of Express Mail Contract 14 to the competitive product list... 14 to the competitive product list.\\1\\ The Postal Service asserts that Express Mail Contract 14 is a...

  13. 77 FR 67839 - New Postal Product

    Science.gov (United States)

    2012-11-14

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing concerning the addition of Priority Mail Contract 48 to the competitive product... Mail Contract 48 to the competitive product list.\\1\\ The Postal Service indicates that the instant...

  14. 78 FR 76863 - New Postal Product

    Science.gov (United States)

    2013-12-19

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2014-12; Order No. 1905] New Postal Product AGENCY... Competitive Multi-Service Agreements with Foreign Postal Operators 1 (MC2010-34) product on the competitive product list. Notice at 3. \\1\\ Notice of United States Postal Service of Filing Functionally Equivalent...

  15. 77 FR 58421 - New Postal Product

    Science.gov (United States)

    2012-09-20

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to add Priority Mail Contract 42 to the competitive product list... request and associated supporting information to add Priority Mail Contract 42 to the competitive product...

  16. 77 FR 60728 - New Postal Product

    Science.gov (United States)

    2012-10-04

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... product list. This notice addresses procedural steps associated with this filing. DATES: Comments are due... competitive product list.\\1\\ The Postal Service asserts that First- Class Package Service Contract 18 is a...

  17. 77 FR 1089 - New Postal Product

    Science.gov (United States)

    2012-01-09

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2012-9; Order No. 1096] New Postal Product AGENCY... Service request to add a Global Direct Contracts 1 contract to the competitive product list. This notice... believes that the instant Agreement should be included within the Global Direct Contracts 1 product because...

  18. 77 FR 305 - New Postal Product

    Science.gov (United States)

    2012-01-04

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... competitive product list. This notice addresses procedural steps associated with the filing. DATES: Comments... Services-Non- Published Rates 3 (GEPS-NPR 3) to the competitive product list.\\1\\ The Postal [[Page 306...

  19. 77 FR 2098 - New Postal Product

    Science.gov (United States)

    2012-01-13

    ... Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to add Global Plus 1C agreements to the competitive product... of two Global Plus 1C agreements, to the competitive product list.\\1\\ The instant agreements are set...

  20. 76 FR 4138 - New Postal Product

    Science.gov (United States)

    2011-01-24

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2011-58; Order No. 652] New Postal Product AGENCY..., which established GREP Contracts 1 as a product, also authorized functionally equivalent agreements to be included within the product, provided that they meet the requirements of 39 U.S.C. 3633. Id. at 1...

  1. 77 FR 51583 - New Postal Product

    Science.gov (United States)

    2012-08-24

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... product list. This notice addresses procedural steps associated with this filing. DATES: Comments are due... competitive product list.\\1\\ The Postal Service asserts that First- Class Package Service Contract 15 is a...

  2. 75 FR 43581 - New Postal Product

    Science.gov (United States)

    2010-07-26

    ... Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing... the competitive product list. The Postal Service has also filed related contracts. This notice... Paragraphs I. Introduction The Postal Service seeks to add a new product, Global Plus 1A, to the competitive...

  3. 75 FR 7201 - New Postal Product

    Science.gov (United States)

    2010-02-18

    ... Postal Product AGENCY: Postal Regulatory Commission. ACTION: Final rule. SUMMARY: The Commission is adding Priority Mail Contract 24 to the Competitive Product List. This action is consistent with changes in a postal reform law. Republication of the lists of market dominant and competitive products is...

  4. 78 FR 65015 - New Postal Product

    Science.gov (United States)

    2013-10-30

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing recent... product list. This notice informs the public of the filings, invites public comment, and takes other... Service Contract 5 to the competitive product list.\\1\\ It is the successor agreement to the contract...

  5. 75 FR 65386 - New Postal Product

    Science.gov (United States)

    2010-10-22

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2011-19; Order No. 562] New Postal Product AGENCY... product list. This notice addresses procedural steps associated with this filing. DATES: Comments are due... GEPS 1 as a product, also authorized functionally equivalent agreements to be included within the...

  6. 78 FR 79023 - New Postal Product

    Science.gov (United States)

    2013-12-27

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing requesting the addition of Priority Mail Contract 73 to the competitive product... supporting information to add Priority Mail Contract 73 to the competitive product list.\\1\\ The Postal...

  7. 78 FR 76334 - New Postal Product

    Science.gov (United States)

    2013-12-17

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2013-13; Order No. 1900] New Postal Product AGENCY...'' of the product. Id. The Postal Service seeks to incorporate by reference the Application for Non... and Order Concerning the Addition of Parcel Select Contract 6 to the Competitive Product List, October...

  8. 78 FR 79025 - New Postal Product

    Science.gov (United States)

    2013-12-27

    ... Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent... product list. This notice informs the public of the filing, invites public comment, and takes other... associated supporting information to add Priority Mail Express Contract 17 to the competitive product list.\\1...

  9. 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

  10. 75 FR 52999 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-08-30

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition... NUCLEAR REGULATORY COMMISSION [NRC-2009-0556] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 8.35...

  11. 75 FR 12804 - Withdrawal of Regulatory Guide 8.6

    Science.gov (United States)

    2010-03-17

    ... ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0103] Withdrawal of Regulatory Guide 8.6 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 8.6, ``Standard Test Procedure for Geiger-M...

  12. 75 FR 16202 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-03-31

    ... Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are available... NUCLEAR REGULATORY COMMISSION [NRC-2008-0644] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide (RG) 1.126...

  13. 75 FR 45171 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-08-02

    ... ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ and through the NRC's Agencywide... NUCLEAR REGULATORY COMMISSION [NRC-2010-0072] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 3.13...

  14. 75 FR 20868 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-04-21

    ... available through the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2009-0351] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.68.2...

  15. 75 FR 42170 - Final Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-07-20

    ... NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2009-0425] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide...

  16. 75 FR 81675 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-12-28

    ... through the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0031] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 4.16...

  17. 75 FR 48381 - Final Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-08-10

    ... NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0274] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of issuance and availability of Regulatory Guide...

  18. 75 FR 37842 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-06-30

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition... NUCLEAR REGULATORY COMMISSION [NRC-2009-0396] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 2.5...

  19. 75 FR 43207 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-07-23

    ... NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2009-0282] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.141...

  20. 75 FR 33361 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-06-11

    ....gov/reading-rm/doc-collections/ . In addition, regulatory guides are available for inspection at the... NUCLEAR REGULATORY COMMISSION [NRC-2009-0308] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.28...

  1. 75 FR 20399 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-04-19

    ... the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2009-0418] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 6.9...

  2. 76 FR 31382 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2011-05-31

    ... the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0287] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 8.2...

  3. 76 FR 24539 - Final Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2011-05-02

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . Electronic copies... NUCLEAR REGULATORY COMMISSION [NRC-2010-0181] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide...

  4. 75 FR 16525 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-04-01

    ... http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are available for... NUCLEAR REGULATORY COMMISSION [NRC-2009-0413] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.11...

  5. 75 FR 27599 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-05-17

    ...'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are available for... NUCLEAR REGULATORY COMMISSION [NRC-2009-0492] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of issuance and availability of Regulatory Guide 6.7...

  6. Characterization of the evolution of the pharmaceutical regulatory environment.

    Science.gov (United States)

    Shafiei, Nader; Ford, James L; Morecroft, Charles W; Lisboa, Paulo J; Taylor, Mark J

    2013-01-01

    This paper is part of a research study that is intended to identify pharmaceutical quality risks induced by the ongoing transformation in the industry. This study establishes the current regulatory context by characterizing the development of the pharmaceutical regulatory environment. The regulatory environment is one of the most important external factors that affects a company's organization, processes, and technological strategy. This is especially the case with the pharmaceutical industry, where its products affect the quality of life of the consumers. The quantitative analysis of regulatory events since 1813 and review of the associated literature resulted in identification of six factors influencing the regulatory environment, namely public health protection, public health promotion, crisis management, harmonization, innovation, and modernization. From 1813 to the 1970s the focus of regulators was centered on crisis management and public health protection-a basic mission that has remained consistent over the years. Since the 1980s a gradual move in the regulatory environment towards a greater focus on public health promotion, international harmonization, innovation, and agency modernization may be seen. The pharmaceutical industry is currently going through changes that affect the way it performs its research, manufacturing, and regulatory activities. The impact of these changes on the approaches to quality risk management requires more understanding. The authors are engaged in research to identify elements of the changes that influence pharmaceutical quality. As quality requirements are an integral part of the pharmaceutical regulations, a comprehensive understanding of these regulations is seen as the first step. The results of this study show that (i) public health protection, public health promotion, crisis management, harmonization, innovation, and modernization are factors that affect regulations in the pharmaceutical industry; (ii) the regulators' main

  7. BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo; Hu, Mintao [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Zhang, Peng [Nanjing Medical University, Nanjing, Jiangsu (China); Cao, Hong [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Wang, Yongzhen [The Second Hospital of Nanjing, Nanjing, Jiangsu (China); Wang, Zheng; Su, Tingting [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China)

    2013-05-10

    Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

  8. Reduction of regulatory risk: a network economic approach

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    Several definitions of regulatory risk are known from the literature. From the perspective of regulatory reform it is important to differentiate between the impact of a given regulatory scheme on the firm's risk exposure and the risk arising from discretionary behavior of regulatory agencies. Whereas the conse-quences of effective regulation in principle are known and accepted, excessive regulatory discretion may cause a strong need for regulatory reform. Regulatory reform focussing on the re...

  9. 76 FR 2930 - Product Change-Parcel Select Negotiated Service Agreement

    Science.gov (United States)

    2011-01-18

    ... POSTAL SERVICE Product Change--Parcel Select Negotiated Service Agreement AGENCY: Postal Service... INFORMATION: The United States Postal Service[reg] hereby gives notice that on December 23, 2010, it filed with the Postal Regulatory [[Page 2931

  10. Safeguards inventory and process monitoring regulatory comparison

    Energy Technology Data Exchange (ETDEWEB)

    Cavaluzzi, Jack M. [Texas A & M Univ., College Station, TX (United States); Gibbs, Philip W. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2013-06-27

    Detecting the theft or diversion of the relatively small amount of fissile material needed to make a nuclear weapon given the normal operating capacity of many of today’s running nuclear production facilities is a difficult task. As throughput increases, the ability of the Material Control and Accountability (MC&A) Program to detect the material loss decreases because the statistical measurement uncertainty also increases. The challenge faced is the ability of current accounting, measurement, and material control programs to detect small yet significant losses under some regulatory approaches can decrease to the point where it is extremely low if not practically non-existent at normal operating capacities. Adding concern to this topic is that there are variations among regulatory bodies as far as what is considered a Significant Quantity (SQ). Some research suggests that thresholds should be lower than those found in any current regulation which if adopted would make meeting detection goals even more difficult. This paper reviews and compares the current regulatory requirements for the MA elements related to physical inventory, uncertainty of the Inventory Difference (ID), and Process Monitoring (PM) in the United States Department of Energy (DOE) and Nuclear Regulatory Commission (NRC), Rosatom of the Russian Federation and the Chinese Atomic Energy Agency (CAEA) of China. The comparison looks at how the regulatory requirements for the implementation of various MA elements perform across a range of operating capacities in example facilities.

  11. Through the regulatory hoop

    International Nuclear Information System (INIS)

    Kirner, N.P.

    1985-01-01

    There are many regulatory hoops through which waste generators, brokers, and disposal site operators must jump to dispose of waste safely. As the proposed exclusionary date of January 1, 1986, approaches, these regulatory hoops have the distinct possibility of multiplying or at least changing shape. The state of Washington, in its role as an Agreement State with the US Nuclear Regulatory Commission, licenses and inspects the commercial operator of the Northwest Compact's low-level radioactive waste disposal site on the Hanford Reservation. Washington has received as much as 53%, or 1.4 million cubic feet per year, of the nation's total volume of waste disposed. To control such a large volume of waste, a regulatory program involving six agencies has developed over the years in Washington

  12. The Text of Tile Master Agreement between the Agency and the United States of America Governing Sales of Source, By- Product and Special Nuclear Materials for research Purposes

    International Nuclear Information System (INIS)

    1974-01-01

    The text of the Master Agreement Governing Sales of Source, Bye Product and Special Nuclear Materials for Research Purposes, which has been concluded between the Agency and the Government of the United States of America, is reproduced herein for the information of all Members,

  13. Identification of regulatory barriers in the production of biodiesel in Brazil; Identificacao de entraves regulatorios na producao de biodiesel no Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Marcelo Santana [Instituto Federal de Educacao, Ciencia e Tecnologia da Bahia (IFBA), Santo Amaro, BA (Brazil)], email: marcelosilva@ifba.edu.br; Teixeira, Francisco Lima Cruz [Universidade Federal da Bahia (UFBA), Salvador, BA (Brazil); Torres, Ednildo Andrade [Universidade Federal da Bahia (CIEnAm/UFBA), Salvador, BA (Brazil). Centro Interdisciplinar de Energia e Ambiente

    2010-07-01

    At a time when biofuels are in evidence in the international arena, it is essential to discuss this new market, in particular the biodiesel. To achieve agricultural and industrial sustainability, the main argument is that replacing oil with biofuels raises some questions, because of the lack of experience with the new productive chains. Due to the way the Biodiesel program is being implemented, this program presents several obstacles. Thus, this study aims to investigate the elements in the regulatory hurdles for the production of Biodiesel. In this work it was adopted qualitative descriptive and exploratory procedures, including desk research and recognition of perceptions through questionnaires to staff intentionally selected from different parts of the productive chain, through non-probabilistic sampling. The survey showed the following barriers: differentiated subsidies, which hinder the production of biodiesel by intensive agriculture and benefit familiar agriculture, do not encourage other regions of the country, or other raw material (animal tallow and ORG); incoherent taxation considering the quantity purchased raw materials; strict control on the region distribution to claim the Social Fuel Seal; it isn't prioritized environmental issues in their regulatory context; there's no prestige to small industry, cooperatives and associations; there is a tax for alcohol applied in biodiesel production; and the law penalizes biodiesel plants for the sale of hydrated alcohol. It was observed that these obstacles hinder the increase in biodiesel production, resulting in countless idle biodiesel plants. In this sense, it was found that the regulatory framework needs to be revised due to the investigated barriers. (author)

  14. Current products and future plan of regulatory technology R and D for risk-informed regulation and applications

    International Nuclear Information System (INIS)

    Song, K. Y.; Lee, C. J.; Kim, W. S.; Jeong, D. W.; Kim, H. J.

    2002-01-01

    The first phase of a R and D project for risk-informed regulation (RIR) and applications (RIA) has been finished. Various results which would be useful for preparing domestic RIR system were accomplished, in areas of safety goals and general principles of RIR, which provide fundamental bases for establishment of RIR system as well as regulatory review guides, which ensure the quality for PSA. RIA guidelines for ISI, IST, MOV, Tech.-Sepc. also have been developed, implementing some pilot plant applications. As essential documents for actual RIR inspection, risk-informed inspection guides and implementation guide for maintenance effectiveness were prepared. In the second phase of R and D, two projects on RIR area will be performed. One is to study on institutionalization of RIR and performance-based regulation, another is to develop a PSA model for regulatory audit as well as regulatory technology for risk monitoring

  15. Regulatory focus, self-efficacy and outcome expectations as drivers of motivation to consume healthy food products

    DEFF Research Database (Denmark)

    Tudoran, Ana Alina; Scholderer, Joachim; Brunsø, Karen

    2012-01-01

    In this paper we apply the principle of RegulatoryFocus Theory to investigate the interaction between self-efficacy and outcomeexpectations on individuals’ intentions to adopt health behaviors. The participants, 959 individuals (Survey 1) and 2400 individuals (Survey 2), reported self-efficacy be......In this paper we apply the principle of RegulatoryFocus Theory to investigate the interaction between self-efficacy and outcomeexpectations on individuals’ intentions to adopt health behaviors. The participants, 959 individuals (Survey 1) and 2400 individuals (Survey 2), reported self...

  16. IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function.

    Science.gov (United States)

    Noval Rivas, Magali; Burton, Oliver T; Oettgen, Hans C; Chatila, Talal

    2016-09-01

    Food allergy is a major health issue, but its pathogenesis remains obscure. Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation. However their role in food allergy is largely unknown. We sought to investigate the role of ILC2s in food allergy. Food allergy-prone mice with a gain-of-function mutation in the IL-4 receptor α chain (Il4raF709) were orally sensitized with food allergens, and the ILC2 compartment was analyzed. The requirement for ILC2s in food allergy was investigated by using Il4raF709, IL-33 receptor-deficient (Il1rl1(-/-)), IL-13-deficient (Il13(-/-)), and IL-4-deficient (Il4(-/-)) mice and by adoptive transfer of in vitro-expanded ILC2s. Direct effects of ILC2s on regulatory T (Treg) cells and mast cells were analyzed in coculture experiments. Treg cell control of ILC2s was assessed in vitro and in vivo. Il4raF709 mice with food allergy exhibit increased numbers of ILC2s. IL-4 secretion by ILC2s contributes to the allergic response by reducing allergen-specific Treg cell and activating mast cell counts. IL-33 receptor deficiency in Il4raF709 Il1rl1(-/-) mice protects against allergen sensitization and anaphylaxis while reducing ILC2 induction. Adoptive transfer of wild-type and Il13(-/-) but not Il4(-/-) ILC2s restored sensitization in Il4raF709 Il1rl1(-/-) mice. Treg cells suppress ILC2s in vitro and in vivo. IL-4 production by IL-33-stimulated ILC2s blocks the generation of allergen-specific Treg cells and favors food allergy. Strategies to block ILC2 activation or the IL-33/IL-33 receptor pathway can lead to innovative therapies in the treatment of food allergy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Production of recombinant AAV vectors encoding insulin-like growth factor I is enhanced by interaction among AAV rep regulatory sequences

    Directory of Open Access Journals (Sweden)

    Dilley Robert

    2009-01-01

    Full Text Available Abstract Background Adeno-associated virus (AAV vectors are promising tools for gene therapy. Currently, their potential is limited by difficulties in producing high vector yields with which to generate transgene protein product. AAV vector production depends in part upon the replication (Rep proteins required for viral replication. We tested the hypothesis that mutations in the start codon and upstream regulatory elements of Rep78/68 in AAV helper plasmids can regulate recombinant AAV (rAAV vector production. We further tested whether the resulting rAAV vector preparation augments the production of the potentially therapeutic transgene, insulin-like growth factor I (IGF-I. Results We constructed a series of AAV helper plasmids containing different Rep78/68 start codon in combination with different gene regulatory sequences. rAAV vectors carrying the human IGF-I gene were prepared with these vectors and the vector preparations used to transduce HT1080 target cells. We found that the substitution of ATG by ACG in the Rep78/68 start codon in an AAV helper plasmid (pAAV-RC eliminated Rep78/68 translation, rAAV and IGF-I production. Replacement of the heterologous sequence upstream of Rep78/68 in pAAV-RC with the AAV2 endogenous p5 promoter restored translational activity to the ACG mutant, and restored rAAV and IGF-I production. Insertion of the AAV2 p19 promoter sequence into pAAV-RC in front of the heterologous sequence also enabled ACG to function as a start codon for Rep78/68 translation. The data further indicate that the function of the AAV helper construct (pAAV-RC, that is in current widespread use for rAAV production, may be improved by replacement of its AAV2 unrelated heterologous sequence with the native AAV2 p5 promoter. Conclusion Taken together, the data demonstrate an interplay between the start codon and upstream regulatory sequences in the regulation of Rep78/68 and indicate that selective mutations in Rep78/68 regulatory elements

  18. Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

    OpenAIRE

    Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

    2016-01-01

    Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employe...

  19. Adverse reactions from essential oil-containing natural flea products exempted from Environmental Protection Agency regulations in dogs and cats.

    Science.gov (United States)

    Genovese, Allison G; McLean, Mary Kay; Khan, Safdar A

    2012-08-01

    To describe adverse effects in dogs and cats exposed to Environmental Protection Agency exempted plant-derived flea preventatives containing mixtures of essential oils. Retrospective study from 2006 to 2008. Records of dog and cat cases were reviewed from the American Society for the Prevention of Cruelty to Animals, Animal Poison Control Center database. Thirty-nine cats and 9 dogs with history of exposure to natural flea preventatives. The following information was retrieved from each incident: number of animals, species involved, frequency, types, onset time, duration of clinical signs, exposure appropriateness, final outcome, and treatment information. Ninety-two percent of animals (n = 44) showed presence of one or more adverse effects. The frequency of adverse effects in dogs (n = 8; 89%) and cats (n = 36; 92%) was similar. Onset time of adverse effects in 39 of 44 animals occurred within 24 hours. The duration of signs in 24 animals ranged from 30 minutes to 149 hours. The products were used as per label in 77% animals (n = 37). Of 28 animals with known outcome, 50% (n = 14) recovered with bathing alone while others received intravenous fluids, muscle relaxants, and anticonvulsive medications. Death (1 cat; n = 1/28; 4%) or euthanasia (1 cat and 1 dog; n = 2/28; 7%) was reported in 3 animals. Dogs and cats can experience significant adverse effects when exposed to plant-derived flea preventatives even when used according to label directions. The number of reports of exposure in cats was higher than dogs, but the frequency of reported adverse effects was similar between the 2 species. Agitation and hypersalivation were common in cats, whereas lethargy and vomiting were common in dogs. © Veterinary Emergency and Critical Care Society 2012.

  20. 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...

  1. Possible regulatory role of phenylalanine ammonia-lyase in the production of anthocyanins in asparagus (Asparagus officinalis L)

    NARCIS (Netherlands)

    Flores, F.B.; Oosterhaven, J.; Martinez-Madrid, M.C.; Romojaro, F.

    2005-01-01

    The regulatory role of phenylalanine ammonia-lyase (PAL) in the light-induced accumulation of anthocyanins in the epidermis of asparagus spears has been analysed. A correlation between the stimulation of PAL activity and the rise in total anthocyanin content has been observed. Light radiation

  2. Regulatory difficulties in a developing country

    International Nuclear Information System (INIS)

    Jacobs, W.R. Jr.

    1978-01-01

    The regulatory agency assigned the task of regulating the initial entry into the field of nuclear power generation by a developing country has a very difficult job. Based on the authors' experience during the start-up and initial operation of Ko-Ri Unit I, the first power reactor in the Republic of Korea, observations on regulatory difficulties and recommendations for improved regulatory effectiveness are offered. The problem areas can be loosely grouped into three general categories: (1) Lack of adequate technical knowledge which is the basis for all effective regulation; (2) Difficulties with understanding and utilization of the required regulatory documentation; (3) Failure to establish the proper regulatory environment. Examples are cited from actual experience during the Ko-Ri Unit I start-up to demonstrate the impact that regulatory activities can have on a plant construction and testing programme. The problems encountered are not unique to developing countries but also exist in the United States of America. Recommendations are offered which should be beneficial to either newly formed regulatory agencies or agencies wishing to improve their abilities and effectiveness. These include: (1) Additional training of regulatory inspectors in plant operations; (2) Additional experience gained by participation in regulatory activities in other countries; (3) Increased attention given to regulatory documents, especially plant technical specifications; (4) Establishment of formal lines of communication between the utility and the regulatory agency; (5) Clear definition of regulatory responsibilities to avoid areas of overlapping jurisdiction; (6) Active participation by the regulatory staff very early in the project. It is hoped that these and other recommendations offered will greatly improve regulatory effectiveness and at the same time demonstrate that when the decision is made to 'go nuclear', a strong commitment must be made to develop and support a technically

  3. 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

  4. 76 FR 59066 - Notice of Regulatory Review Plan

    Science.gov (United States)

    2011-09-23

    ... [No. 2011-N-10] Notice of Regulatory Review Plan AGENCY: Federal Housing Finance Agency. ACTION... of and requesting comments on the FHFA interim regulatory review plan for review of existing... comments on all aspects of the interim regulatory review plan, including legal and policy considerations...

  5. Reconstruction of a metabolic regulatory network in Escherichia coli for purposeful switching from cell growth mode to production mode in direct GABA fermentation from glucose.

    Science.gov (United States)

    Soma, Yuki; Fujiwara, Yuri; Nakagawa, Takuya; Tsuruno, Keigo; Hanai, Taizo

    2017-09-01

    γ-aminobutyric acid (GABA) is a drug and functional food additive and is used as a monomer for producing the biodegradable plastic, polyamide 4. Recently, direct GABA fermentation from glucose has been developed as an alternative to glutamate-based whole cell bioconversion. Although total productivity in fermentation is determined by the specific productivity and cell amount responsible for GABA production, the optimal metabolic state for GABA production conflicts with that for bacterial cell growth. Herein, we demonstrated metabolic state switching from the cell growth mode based on the metabolic pathways of the wild type strain to a GABA production mode based on a synthetic metabolic pathway in Escherichia coli through rewriting of the metabolic regulatory network and pathway engineering. The GABA production mode was achieved by multiple strategies such as conditional interruption of the TCA and glyoxylate cycles, engineering of GABA production pathway including a bypass for precursor metabolite supply, and upregulation of GABA transporter. As a result, we achieved 3-fold improvement in total GABA production titer and yield (4.8g/L, 49.2% (mol/mol glucose)) in batch fermentation compared to the case without metabolic state switching (1.6g/L, 16.4% (mol/mol glucose)). This study reports the highest GABA production performance among previous reports on GABA fermentation from glucose using engineered E. coli. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  6. 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.

  7. Department of Transportation Agency Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... result in more effective public participation. This publication in the Federal Register does not impose... contracting issues associated with subcontracting with Small Business, Small Disadvantaged Business, and Women... and Water Efficiency, Renewable Energy Technologies, Occupational Safety, and Drug-Free Workplace...

  8. Environmental Protection Agency Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-04-26

    ... more easily and live more healthy lives. Building on that, EPA will develop a comprehensive strategy... stakeholders working with us to identify the most practical and effective solutions to problems, and we stress...; Under the Federal Food, Drug, and Cosmetic Act: Actions regarding pesticide tolerances and food additive...

  9. Functional characterization of a three-component regulatory system involved in quorum sensing-based regulation of peptide antibiotic production in Carnobacterium maltaromaticum

    Directory of Open Access Journals (Sweden)

    Quadri Luis EN

    2006-10-01

    Full Text Available Abstract Background Quorum sensing is a form of cell-to-cell communication that allows bacteria to control a wide range of physiological processes in a population density-dependent manner. Production of peptide antibiotics is one of the processes regulated by quorum sensing in several species of Gram-positive bacteria, including strains of Carnobacterium maltaromaticum. This bacterium and its peptide antibiotics are of interest due to their potential applications in food preservation. The molecular bases of the quorum sensing phenomenon controlling peptide antibiotic production in C. maltaromaticum remain poorly understood. The present study was aimed at gaining a deeper insight into the molecular mechanism involved in quorum sensing-mediated regulation of peptide antibiotic (bacteriocin production by C. maltaromaticum. We report the functional analyses of the CS (autoinducer-CbnK (histidine protein kinase-CbnR (response regulator three-component regulatory system and the three regulated promoters involved in peptide antibiotic production in C. maltaromaticum LV17B. Results CS-CbnK-CbnR system-dependent activation of carnobacterial promoters was demonstrated in both homologous and heterologous hosts using a two-plasmid system with a β-glucuronidase (GusA reporter read-out. The results of our analyses support a model in which the CbnK-CbnR two-component signal transduction system is necessary and sufficient to transduce the signal of the peptide autoinducer CS into the activation of the promoters that drive the expression of the genes required for production of the carnobacterial peptide antibiotics and the immunity proteins that protect the producer bacterium. Conclusions The CS-CbnK-CbnR triad forms a three-component regulatory system by which production of peptide antibiotics by C. maltaromaticum LV17B is controlled in a population density-dependent (or cell proximity-dependent manner. This regulatory mechanism would permit the bacterial

  10. Scientific, economic, regulatory, and ethical challenges of bringing science-based pediatric nutrition products to the U.S. market and ensuring their availability for patients.

    Science.gov (United States)

    Merritt, Russell J; Goldsmith, Arthur H

    2014-11-01

    Many nutrition products and related drugs are unavailable or not consistently available to clinicians despite a body of clinical data and experience supporting their use. Many of these can be related to drug shortages that have increased since 2009. In addition, there are potentially useful products that are not approved for a specific use or are no longer being manufactured. This review broadly examines the product availability gap from the perspectives of a clinician/former nutrition industry medical director and an economist. The process of pediatric nutrition product and related drug innovation, as well as its drivers and the steps involved in bringing a product to market, is first described. This is followed by an assessment of factors influencing product availability beyond the innovation process, including regulatory issues, manufacturing compliance, purchasing practices, and other factors related to drug and nutrition product pricing and reimbursement. Three pediatric case examples are reviewed and placed in the context of the prior review. Last, recent and future possible steps toward closing the product availability gap are discussed. © 2014 American Society for Parenteral and Enteral Nutrition.

  11. Serotonin decreases the production of Th1/Th17 cytokines and elevates the frequency of regulatory CD4+ T cell subsets in multiple sclerosis patients.

    Science.gov (United States)

    Sacramento, Priscila M; Monteiro, Clarice; Dias, Aleida S O; Kasahara, Taissa M; Ferreira, Thaís B; Hygino, Joana; Wing, Ana Cristina; Andrade, Regis M; Rueda, Fernanda; Sales, Marisa C; Vasconcelos, Claudia Cristina; Bento, Cleonice A M

    2018-05-02

    Excessive levels of pro-inflammatory cytokines in the central nervous system (CNS) are associated with reduced serotonin (5-HT) synthesis, a neurotransmitter with diverse immune effects. In this study, we evaluated the ability of exogenous 5-HT to modulate the T-cell behavior of patients with multiple sclerosis (MS), a demyelinating autoimmune disease mediated by Th1 and Th17 cytokines. Here, 5-HT attenuated, in vitro, T-cell proliferation and Th1 and Th17 cytokines production in cell cultures from MS patients. Additionally, 5-HT reduced IFN-γ and IL-17 release by CD8 + T-cells. By contrast, 5-HT increased IL-10 production by CD4 + T-cells from MS patients. A more accurate analysis of these IL-10-secreting CD4 + T-cells revealed that 5-HT favors the expansion of FoxP3 + CD39 + regulatory T cells (Tregs) and type 1 regulatory T cells. Notably, this neurotransmitter also elevated the frequency of Treg17 cells, a novel regulatory T-cell subset. The effect of 5-HT in up-regulating CD39 + Treg and Treg17 cells was inversely correlated with the number of active brain lesions. Finally, in addition to directly reducing cytokine production by purified Th1 and Th17 cells, 5-HT enhanced in vitro Treg function. In summary, our data suggest that serotonin may play a protective role in the pathogenesis of MS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. 76 FR 28102 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2011-05-13

    ..., Probabilistic Risk Assessment Branch, Division of Risk Analysis, Office of Nuclear Regulatory Research, U.S... results of risk analyses are used to help justify regulatory action. As such, the principles, process, and... NUCLEAR REGULATORY COMMISSION [NRC-2009-0385] Notice of Issuance of Regulatory Guide AGENCY...

  13. 75 FR 2894 - Withdrawal of Regulatory Guide 1.148

    Science.gov (United States)

    2010-01-19

    ... downloading through the NRC's public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are also available for... NUCLEAR REGULATORY COMMISSION [NRC-2010-0013] Withdrawal of Regulatory Guide 1.148 AGENCY: Nuclear...

  14. 75 FR 70044 - Withdrawal of Regulatory Guide 1.39

    Science.gov (United States)

    2010-11-16

    ... downloading through the NRC's public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doollectionsc-c . Regulatory guides are also available for... NUCLEAR REGULATORY COMMISSION [NRC-2010-0354] Withdrawal of Regulatory Guide 1.39 AGENCY: Nuclear...

  15. 76 FR 35922 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2011-06-20

    .... Proposed Revision 1 of Regulatory Guide (RG) 8.4, ``Personnel Monitoring Device--Direct-Reading Pocket...'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are available for... NUCLEAR REGULATORY COMMISSION [NRC-2010-0148] Notice of Issuance of Regulatory Guide AGENCY...

  16. 78 FR 44165 - Nuclear Regulatory Commission Enforcement Policy

    Science.gov (United States)

    2013-07-23

    ... NUCLEAR REGULATORY COMMISSION [NRC-2013-0159] Nuclear Regulatory Commission Enforcement Policy AGENCY: Nuclear Regulatory Commission. ACTION: Enforcement policy; request for comment. SUMMARY: The U.S... Policy. In SRM-SECY-12-0047, ``Revisions to the Nuclear Regulatory Commission Enforcement Policy,'' dated...

  17. 76 FR 63668 - Guidelines for Preparing and Reviewing Licensing Applications for the Production of Radioisotopes

    Science.gov (United States)

    2011-10-13

    ..., Research and Test Reactors Projects Branch, Division of Policy and Rulemaking, Office of Nuclear Reactor... NUCLEAR REGULATORY COMMISSION [NRC-2011-0135] Guidelines for Preparing and Reviewing Licensing Applications for the Production of Radioisotopes AGENCY: Nuclear Regulatory Commission. ACTION: Draft interim...

  18. 77 FR 28467 - Identifying and Reducing Regulatory Burdens

    Science.gov (United States)

    2012-05-14

    ... online wherever practicable. Sec. 3. Setting Priorities. In implementing and improving their... regulatory priorities, to promote public participation in retrospective review, to modernize our regulatory..., agencies shall give priority, consistent with law, to those initiatives that will produce significant...

  19. Regulatory network controlling extracellular proteins in Erwinia carotovora subsp. carotovora: FlhDC, the master regulator of flagellar genes, activates rsmB regulatory RNA production by affecting gacA and hexA (lrhA) expression.

    Science.gov (United States)

    Cui, Yaya; Chatterjee, Asita; Yang, Hailian; Chatterjee, Arun K

    2008-07-01

    Erwinia carotovora subsp. carotovora produces an array of extracellular proteins (i.e., exoproteins), including plant cell wall-degrading enzymes and Harpin, an effector responsible for eliciting hypersensitive reaction. Exoprotein genes are coregulated by the quorum-sensing signal, N-acyl homoserine lactone, plant signals, an assortment of transcriptional factors/regulators (GacS/A, ExpR1, ExpR2, KdgR, RpoS, HexA, and RsmC) and posttranscriptional regulators (RsmA, rsmB RNA). rsmB RNA production is positively regulated by GacS/A, a two-component system, and negatively regulated by HexA (PecT in Erwinia chrysanthemi; LrhA [LysR homolog A] in Escherichia coli) and RsmC, a putative transcriptional adaptor. While free RsmA, an RNA-binding protein, promotes decay of mRNAs of exoprotein genes, binding of RsmA with rsmB RNA neutralizes the RsmA effect. In the course of studies of GacA regulation, we discovered that a locus bearing strong homology to the flhDC operon of E. coli also controls extracellular enzyme production. A transposon insertion FlhDC(-) mutant produces very low levels of pectate lyase, polygalacturonase, cellulase, protease, and E. carotovora subsp. carotovora Harpin (Harpin(Ecc)) and is severely attenuated in its plant virulence. The production of these exoproteins is restored in the mutant carrying an FlhDC(+) plasmid. Sequence analysis and transcript assays disclosed that the flhD operon of E. carotovora subsp. carotovora, like those of other enterobacteria, consists of flhD and flhC. Complementation analysis revealed that the regulatory effect requires functions of both flhD and flhC products. The data presented here show that FlhDC positively regulates gacA, rsmC, and fliA and negatively regulates hexA (lrhA). Evidence shows that FlhDC controls extracellular protein production through cumulative effects on hexA and gacA. Reduced levels of GacA and elevated levels of HexA in the FlhDC(-) mutant are responsible for the inhibition of rsmB RNA

  20. Regulatory Network Controlling Extracellular Proteins in Erwinia carotovora subsp. carotovora: FlhDC, the Master Regulator of Flagellar Genes, Activates rsmB Regulatory RNA Production by Affecting gacA and hexA (lrhA) Expression▿

    Science.gov (United States)

    Cui, Yaya; Chatterjee, Asita; Yang, Hailian; Chatterjee, Arun K.

    2008-01-01

    Erwinia carotovora subsp. carotovora produces an array of extracellular proteins (i.e., exoproteins), including plant cell wall-degrading enzymes and Harpin, an effector responsible for eliciting hypersensitive reaction. Exoprotein genes are coregulated by the quorum-sensing signal, N-acyl homoserine lactone, plant signals, an assortment of transcriptional factors/regulators (GacS/A, ExpR1, ExpR2, KdgR, RpoS, HexA, and RsmC) and posttranscriptional regulators (RsmA, rsmB RNA). rsmB RNA production is positively regulated by GacS/A, a two-component system, and negatively regulated by HexA (PecT in Erwinia chrysanthemi; LrhA [LysR homolog A] in Escherichia coli) and RsmC, a putative transcriptional adaptor. While free RsmA, an RNA-binding protein, promotes decay of mRNAs of exoprotein genes, binding of RsmA with rsmB RNA neutralizes the RsmA effect. In the course of studies of GacA regulation, we discovered that a locus bearing strong homology to the flhDC operon of E. coli also controls extracellular enzyme production. A transposon insertion FlhDC− mutant produces very low levels of pectate lyase, polygalacturonase, cellulase, protease, and E. carotovora subsp. carotovora Harpin (HarpinEcc) and is severely attenuated in its plant virulence. The production of these exoproteins is restored in the mutant carrying an FlhDC+ plasmid. Sequence analysis and transcript assays disclosed that the flhD operon of E. carotovora subsp. carotovora, like those of other enterobacteria, consists of flhD and flhC. Complementation analysis revealed that the regulatory effect requires functions of both flhD and flhC products. The data presented here show that FlhDC positively regulates gacA, rsmC, and fliA and negatively regulates hexA (lrhA). Evidence shows that FlhDC controls extracellular protein production through cumulative effects on hexA and gacA. Reduced levels of GacA and elevated levels of HexA in the FlhDC− mutant are responsible for the inhibition of rsmB RNA production

  1. 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

  2. A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2.

    Science.gov (United States)

    Shi, Qian; Wang, Qiu; Li, Jing; Zhou, Xiaohui; Fan, Huimin; Wang, Fenghua; Liu, Haiyun; Sun, Xiangjun; Sun, Xiaodong

    2015-12-01

    Inflammatory status of RPE cells induced by A2E is essential in the development of AMD. Recent research indicated T-cell immunity was involved in the pathological progression of AMD. This study was designed to investigate how A2E suppresses immunoregulatory function of RPE cells in T-cell immunity in vitro. Mouse RPE cells or human ARPE19 cells were stimulated with A2E, and co-cultured with naïve T cells under Th1, Th2, Th17, and regulatory T cell (Treg) polarization conditions. The intracellular cytokines or transcript factors of the induced T-cells subset were detected with flow cytometer and qRT-PCR. The ROS levels were detected, and the factors and possible pathways involved in the A2E-laden RPE cells were analyzed through neutralization antibody of IL-1β and inhibitors of related pathways. The A2E reduced regulatory function of RPE cells in Treg differentiation. The A2E-laden RPE cells promoted polarization of Th1 cells in vitro, but not Th2 or Th17 differentiation. The A2E induced RPE cells to release inflammatory cytokines and ROS, but PGE2 production was inhibited. Through neutralization of IL-1β or inhibition of COX2-PGE2 pathways, A2E-laden RPE cells expressed reduced effect in inducing Th1 cells. The A2E inhibited regulatory function of RPE cells in suppressing Th1 cell immunity in vitro through production of IL-1β and inhibition of PGE2. Our data indicate that A2E could suppress immunoregulatory function of RPE cells and adaptive immunity might play a role in the immune pathogenesis of AMD.

  3. Nuclear regulatory decision making

    International Nuclear Information System (INIS)

    2005-01-01

    The fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear utilities operate their plants at all times in an acceptably safe manner. In meeting this objective, the regulatory body should strive to ensure that its regulatory decisions are technically sound, consistent from case to case, and timely. In addition, the regulator must be aware that its decisions and the circumstances surrounding those decisions can affect how its stakeholders, such as government policy makers, the industry it regulates, and the public, view it as an effective and credible regulator. In order to maintain the confidence of those stakeholders, the regulator should make sure that its decisions are transparent, have a clear basis in law and regulations, and are seen by impartial observers to be fair to all parties. Based on the work of a Nuclear Energy Agency (NEA) expert group, this report discusses some of the basic principles and criteria that a regulatory body should consider in making decisions and describes the elements of an integrated framework for regulatory decision making. (author)

  4. Pleiotropic regulatory genes bldA, adpA and absB are implicated in production of phosphoglycolipid antibiotic moenomycin.

    Science.gov (United States)

    Makitrynskyy, Roman; Ostash, Bohdan; Tsypik, Olga; Rebets, Yuriy; Doud, Emma; Meredith, Timothy; Luzhetskyy, Andriy; Bechthold, Andreas; Walker, Suzanne; Fedorenko, Victor

    2013-10-23

    Unlike the majority of actinomycete secondary metabolic pathways, the biosynthesis of peptidoglycan glycosyltransferase inhibitor moenomycin in Streptomyces ghanaensis does not involve any cluster-situated regulators (CSRs). This raises questions about the regulatory signals that initiate and sustain moenomycin production. We now show that three pleiotropic regulatory genes for Streptomyces morphogenesis and antibiotic production-bldA, adpA and absB-exert multi-layered control over moenomycin biosynthesis in native and heterologous producers. The bldA gene for tRNA(Leu)UAA is required for the translation of rare UUA codons within two key moenomycin biosynthetic genes (moe), moeO5 and moeE5. It also indirectly influences moenomycin production by controlling the translation of the UUA-containing adpA and, probably, other as-yet-unknown repressor gene(s). AdpA binds key moe promoters and activates them. Furthermore, AdpA interacts with the bldA promoter, thus impacting translation of bldA-dependent mRNAs-that of adpA and several moe genes. Both adpA expression and moenomycin production are increased in an absB-deficient background, most probably because AbsB normally limits adpA mRNA abundance through ribonucleolytic cleavage. Our work highlights an underappreciated strategy for secondary metabolism regulation, in which the interaction between structural genes and pleiotropic regulators is not mediated by CSRs. This strategy might be relevant for a growing number of CSR-free gene clusters unearthed during actinomycete genome mining.

  5. Teacher agency:

    DEFF Research Database (Denmark)

    Robinson, Sarah; Priestley, Mark; Biesta, Gert

    2015-01-01

    The concept of teacher agency has emerged in recent literature as an alternative means of understanding how teachers might enact practice and engage with policy (e.g. Lasky, 2005; Leander & Osbourne, 2008; Ketelaar et al., 2012; Priestley, Biesta & Robinson, 2013). But what is agency? Agency rema...

  6. Advertising Agencies

    DEFF Research Database (Denmark)

    Moeran, Brian

    2015-01-01

    Advertising agencies are the most significant organizations in the development of advertising and marketing worldwide. An advertising agency is an independent service company, composed of business, marketing and creative people, who develop, prepare, and place advertising in advertising media...... for their clients, the advertisers, who are in search of customers for their goods and services. Agencies thus mediate between three different but interlocking social groups: industry, media, and consumers. The history of advertising is largely the history of the advertising agencies that have served the needs....... This article is concerned with the origins, early developments, organization, compensation arrangements, and accounts of contemporary full-service advertising agencies....

  7. Predicted coal production trends in Kentucky: The results of available coal resources, coal quality demands, and regulatory factors

    International Nuclear Information System (INIS)

    Watson, W.D.

    1993-01-01

    Many factors affect the viability of regional coal production markets including (1) coal quality and recoverable tonnage, (2) coal mining cost, (3) the regional and time varying patterns of coal demand growth, (4) regulations and other institutional constraints that affect coal demand and utilization, and (5) the regional array of coal transport modes and rates. This analysis integrates these factors into an assessment of coal production prospects (separately) for eastern and western Kentucky coal producing counties for the decade of the 90's. The integration indicates that eastern Kentucky coal production will peak and begin to decline by the end of the decade whereas western Kentucky coal production will continue to grow. No single factor explains these trends. There is plenty of available minable coal. The combination of changes in environmental regulations, some increase in coal mining costs, and the mining-out of low sulfur reserves are the main factors that account for the production trends

  8. Mobile Source Emissions Regulatory Compliance Data Inventory

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Mobile Source Emissions Regulatory Compliance Data Inventory data asset contains measured summary compliance information on light-duty, heavy-duty, and non-road...

  9. Disruption of the nitrogen regulatory gene AcareA in Acremonium chrysogenum leads to reduction of cephalosporin production and repression of nitrogen metabolism.

    Science.gov (United States)

    Li, Jinyang; Pan, Yuanyuan; Liu, Gang

    2013-12-01

    AcareA, encoding a homologue of the fungal nitrogen regulatory GATA zinc-finger proteins, was cloned from Acremonium chrysogenum. Gene disruption and genetic complementation revealed that AcareA was required for nitrogen metabolism and cephalosporin production. Disruption of AcareA resulted in growth defect in the medium using nitrate, uric acid and low concentration of ammonium, glutamine or urea as sole nitrogen source. Transcriptional analysis showed that the transcription of niaD/niiA was increased drastically when induced with nitrate in the wild-type and AcareA complemented strains but not in AcareA disruption mutant. Consistent with the reduction of cephalosporin production, the transcription of pcbAB, cefD2, cefEF and cefG encoding the enzymes for cephalosporin production was reduced in AcareA disruption mutant. Band shift assays showed that AcAREA bound to the promoter regions of niaD, niiA and the bidirectional promoter region of pcbAB-pcbC. Sequence analysis showed that all the AcAREA binding sites contain the consensus GATA elements. These results indicated that AcAREA plays an important role both in the regulation of nitrogen metabolism and cephalosporin production in A. chrysogenum. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Innovative training techniques in the Canadian nuclear regulatory environment

    International Nuclear Information System (INIS)

    Martin, D.J.

    1996-01-01

    One of the contributors to the safety of nuclear installations is properly-trained personnel. This applies equally to the staff of a regulatory agency, as they are charged with the task of evaluating the safety of installations and operations involving radioactive materials. In 1990, the nuclear regulatory agency of Canada, the Atomic Energy Control Board, set up a Training Center to train AECB staff and to provide assistance to foreign regulatory agencies who had asked for such assistance. In setting up the Training Centre, the authors considered factors which adversely affect the efficacy of training courses. The technical content must, of course, be of sufficiently high quality, but there are other, significant factors which are independent of the content: consider a presentation in which the lecturer shows a slide which is unreadable from the back of the room. The training value of this slide is zero, even though the content may be sound. Pursuing this thought, they decided to examine the mechanics of presentations and the form of training materials, with a view to optimizing their effectiveness in training. The results of this examination were that they decided to use three technologies as the basis for production of training, support and presentation materials. This paper briefly describes these technologies and their advantages. The technologies are: desktop publishing, video and multimedia

  11. 76 FR 75786 - International Product and Price Changes

    Science.gov (United States)

    2011-12-05

    ... POSTAL SERVICE 39 CFR Part 20 International Product and Price Changes AGENCY: Postal Service TM... Service, International Mail Manual (IMM[supreg]), to reflect the prices, product features, and.... SUPPLEMENTARY INFORMATION: New prices are available under Docket Number CP2012-2 on the Postal Regulatory...

  12. 76 FR 6587 - Pennsylvania Regulatory Program

    Science.gov (United States)

    2011-02-07

    ... [PA-159-FOR; OSM 2010-0017] Pennsylvania Regulatory Program AGENCY: Office of Surface Mining... remove a required amendment to the Pennsylvania regulatory program (the ``Pennsylvania program'') under... program amendment codified in the Federal regulations, Pennsylvania has submitted information that it...

  13. 76 FR 64043 - Iowa Regulatory Program

    Science.gov (United States)

    2011-10-17

    ...) Requirements for permits for special categories of mining. 27--40.41(207) Permanent regulatory program--small... DEPARTMENT OF THE INTERIOR Office of Surface Mining Reclamation and Enforcement 30 CFR Part 915 [Docket No. IA-016-FOR; Docket ID: OSM-2011-0014] Iowa Regulatory Program AGENCY: Office of Surface Mining...

  14. Environmental regulatory update table, March 1989

    International Nuclear Information System (INIS)

    Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1989-04-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

  15. Environmental Regulatory Update Table, April 1989

    International Nuclear Information System (INIS)

    Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1989-05-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

  16. Environmental Regulatory Update Table, August 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M., Hawkins, G.T.; Salk, M.S.

    1991-09-01

    This Environmental Regulatory Update Table (August 1991) provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  17. Environmental Regulatory Update Table, December 1989

    International Nuclear Information System (INIS)

    Houlbert, L.M.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1990-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

  18. Environmental Regulatory Update Table, December 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1992-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  19. Environmental Regulatory Update Table, August 1990

    International Nuclear Information System (INIS)

    Houlberg, L.M.; Nikbakht, A.; Salk, M.S.

    1990-09-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

  20. Environmental Regulatory Update Table, October 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-11-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  1. Environmental Regulatory Update Table, November 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-12-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  2. Environmental Regulatory Update Table, September 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-10-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  3. Environmental regulatory update table, July 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-08-01

    This Environmental Regulatory Update Table (July 1991) provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  4. Engineered protein degradation of farnesyl pyrophosphate synthase is an effective regulatory mechanism to increase monoterpene production in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Peng, Bingyin; Nielsen, Lars K.; Kampranis, Sotirios C

    2018-01-01

    Monoterpene production in Saccharomyces cerevisae requires the introduction of heterologous monoterpene synthases (MTSs). The endogenous farnesyl pyrosphosphate synthase (FPPS; Erg20p) competes with MTSs for the precursor geranyl pyrophosphate (GPP), which limits the production of monoterpenes. ERG......20 is an essential gene that cannot be deleted and transcriptional down-regulation of ERG20 has failed to improve monoterpene production. Here, we investigated an N-degron-dependent protein degradation strategy to down-regulate Erg20p activity. Degron tagging decreased GFP protein half......-life drastically to 1 h (degron K3K15) or 15 min (degrons KN113 and KN119). Degron tagging of ERG20 was therefore paired with a sterol responsive promoter to ensure sufficient metabolic flux to essential downstream sterols despite the severe destabilisation effect of degron tagging. A dual monoterpene...

  5. Identification of choriogenin cis-regulatory elements and production of estrogen-inducible, liver-specific transgenic Medaka.

    Science.gov (United States)

    Ueno, Tetsuro; Yasumasu, Shigeki; Hayashi, Shinji; Iuchi, Ichiro

    2004-07-01

    Choriogenins (chg-H, chg-L) are precursor proteins of egg envelope of medaka and synthesized in the spawning female liver in response to estrogen. We linked a gene construct chg-L1.5 kb/GFP (a 1.5 kb 5'-upstream region of the chg-L gene fused with a green fluorescence protein (GFP) gene) to another construct emgb/RFP (a cis-regulatory region of embryonic globin gene fused with an RFP gene), injected the double fusion gene construct into 1- or 2-cell-stage embryos, and selected embryos expressing the RFP in erythroid cells. From the embryos, we established two lines of chg-L1.5 kb/GFP-emgb/RFP-transgenic medaka. The 3-month-old spawning females and estradiol-17beta (E2)-exposed males displayed the liver-specific GFP expression. The E2-dependent GFP expression was detected in the differentiating liver of the stage 37-38 embryos. In addition, RT-PCR and whole-mount in situ hybridization showed that the E2-dependent chg expression was found in the liver of the stage 34 embryos of wild medaka, suggesting that such E2-dependency is achieved shortly after differentiation of the liver. Analysis using serial deletion mutants fused with GFP showed that the region -426 to -284 of the chg-L gene or the region -364 to -265 of the chg-H gene had the ability to promote the E2-dependent liver-specific GFP expression of its downstream gene. Further analyses suggested that an estrogen response element (ERE) at -309, an ERE half-site at -330 and a binding site for C/EBP at -363 of the chg-L gene played important roles in its downstream chg-L gene expression. In addition, this transgenic medaka may be useful as one of the test animals for detecting environmental estrogenic steroids.

  6. 78 FR 14635 - HACCP Plan Reassessment for Not-Ready-To-Eat Comminuted Poultry Products and Related Agency...

    Science.gov (United States)

    2013-03-07

    ... it will determine whether the association of NRTE meat or poultry product with an illness outbreak... and activities on the basis of race, color, national origin, gender, religion, age, disability...

  7. 77 FR 72686 - HACCP Plan Reassessment for Not-Ready-To-Eat Comminuted Poultry Products and Related Agency...

    Science.gov (United States)

    2012-12-06

    ..., political beliefs, sexual orientation, and marital or family status. (Not all prohibited bases apply to all... biological hazards, particularly Salmonella. An establishment that produces comminuted poultry and has... for NRTE comminuted poultry products adequately address biological hazards, Salmonella in particular...

  8. 78 FR 51732 - The Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant...

    Science.gov (United States)

    2013-08-21

    ..., and the FDA Orphan Products Grant program to participants representing pharmaceutical, biotechnology... treatment of a rare disease or condition in order to discuss the processes for putting together an...

  9. Trichomonas vaginalis α-Actinin 2 Modulates Host Immune Responses by Inducing Tolerogenic Dendritic Cells via IL-10 Production from Regulatory T Cells.

    Science.gov (United States)

    Lee, Hye-Yeon; Kim, Juri; Ryu, Jae-Sook; Park, Soon-Jung

    2017-08-01

    Trichomonas vaginalis is a pathogen that triggers severe immune responses in hosts. T. vaginalis α-actinin 2, Tvα-actinin 2, has been used to diagnose trichomoniasis. This study was undertaken to examine the role of Tvα-actinin 2 as an antigenic molecule to induce immune responses from humans. Western blot analysis using anti-Tvα-actinin 2 antibodies indicated its presence in the secreted proteins of T. vaginalis. ELISA was employed to measure cytokine production by vaginal epithelial cells, prostate cells, mouse dendritic cells (DCs), or T cells stimulated with T. vaginalis or Tvα-actinin 2 protein. Both T. vaginalis and rTvα-actinin 2 induced cytokine production from epithelial cell lines, including IL-10. Moreover, CD4+CD25- regulatory T cells (Treg cells) incubated with rTvα-actinin 2-treated DCs produced high levels of IL-10. These data indicate that Tvα-actinin 2 modulates immune responses via IL-10 production by Treg cells.

  10. Expression of Genes Involved in Bacteriocin Production and Self-Resistance in Lactobacillus brevis 174A Is Mediated by Two Regulatory Proteins.

    Science.gov (United States)

    Noda, Masafumi; Miyauchi, Rumi; Danshiitsoodol, Narandalai; Matoba, Yasuyuki; Kumagai, Takanori; Sugiyama, Masanori

    2018-04-01

    We have previously shown that the lactic acid bacterium Lactobacillus brevis 174A, isolated from Citrus iyo fruit, produces a bacteriocin designated brevicin 174A, which is comprised of two antibacterial polypeptides (designated brevicins 174A-β and 174A-γ). We have also found a gene cluster, composed of eight open reading frames (ORFs), that contains genes for the biosynthesis of brevicin 174A, self-resistance to its own bacteriocin, and two transcriptional regulatory proteins. Some lactic acid bacterial strains have a system to start the production of bacteriocin at an adequate stage of growth. Generally, the system consists of a membrane-bound histidine protein kinase (HPK) that senses a specific environmental stimulus and a corresponding response regulator (RR) that mediates the cellular response. We have previously shown that although the HPK- and RR-encoding genes are not found on the brevicin 174A biosynthetic gene cluster in the 174A strain, two putative regulatory genes, designated breD and breG , are in the gene cluster. In the present study, we demonstrate that the expression of brevicin 174A production and self-resistance is positively controlled by two transcriptional regulatory proteins, designated BreD and BreG. BreD is expressed together with BreE as the self-resistance determinant of L. brevis 174A. DNase I footprinting analysis and a promoter assay demonstrated that BreD binds to the breED promoter as a positive autoregulator. The present study also demonstrates that BreG, carrying a transmembrane domain, binds to the common promoter of breB and breC , encoding brevicins 174A-β and 174A-γ, respectively, for positive regulation. IMPORTANCE The problem of the appearance of bacteria that are resistant to practical antibiotics and the increasing demand for safe foods have increased interest in replacing conventional antibiotics with bacteriocin produced by the lactic acid bacteria. This antibacterial substance can inhibit the growth of pathogenic

  11. Collaborative models for the joint production of core health technology assessments: negative and positive aspects for the joint work of different European agencies.

    Science.gov (United States)

    Lo Scalzo, Alessandra; Vicari, Nicola; Corio, Mirella; Perrini, Maria Rosaria; Jefferson, Tom; Gillespie, Francesca; Cerbo, Marina

    2014-11-01

    The purpose of the European network for Health Technology Assessment (EUnetHTA) is to make HTA agencies collaborate sharing methods and tools thus avoiding duplication of evaluative efforts and allowing resource savings. From 2010 to 2012, the activities of the network were carried out through EUnetHTA Joint Action 1 and Work Package 4 Strand B aimed at producing two Core HTAs with two main objectives: to test the Web based Core model and the collaborative working models. Our objective in this article is to give an historical record of the Work Package activities highlighting what worked and what did not in the collaboration of researchers' groups coming from different agencies. A retrospective description of all the steps for the joint production of the two Core HTAs is provided starting from the first step of selecting technologies of common interest. Primary researchers' views on the whole process have been collected through a semi-structured telephonic interview supported by a questionnaire. Coordinators views were gathered during internal meetings and validated. Majority of respondents thought topic selection procedure was not clear and well managed. About collaborative models, small groups were seen to enable more exchange, whatever the model. According to coordinators, loss of expertise and experience during the production process, different languages, and novelty of the Online Tool were main barriers. Lessons learned from this first experience in Joint Action 1 paved the path for the collaboration in Joint Action 2, as it allowed enhancements and changes in models of collaborations and coordination.

  12. 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

  13. 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.)

  14. Exhibition; Image display agency

    International Nuclear Information System (INIS)

    Normazlin Ismail

    2008-01-01

    This article touches on the role of Malaysian Nuclear Agency as nuclear research institutions to promote, develop and encourage the peaceful uses of nuclear technology in its agricultural, medical, manufacturing, industrial, health and environment for the development of the country running successfully. Maturity of Malaysian Nuclear Agency in dealing with nuclear technology that are very competitive and globalization cannot be denied. On this basis Malaysian Nuclear Agency was given the responsibility to strengthen the nuclear technology in Malaysia. One way is through an exhibition featuring the research, discoveries and new technology products of the nuclear technology. Through this exhibition is to promote the nuclear technology and introduce the image of the agency in the public eye. This article also states a number of exhibits entered by the Malaysian Nuclear Agency and achievements during the last exhibition. Authors hope that the exhibition can be intensified further in the future.

  15. Diplomatic agency

    DEFF Research Database (Denmark)

    Adler-Nissen, Rebecca

    2016-01-01

    diplomatic agency has been conceptualized in International Relations theory (English School, game theory, Foreign Policy Analysis, constructivism, practice theory, post-positivism) before presenting and exemplifying major and overlapping types of diplomatic agency, including communication, negotiation......Diplomatic agency is intriguing. On the one hand, diplomats are crucial to the management of day-to-day international relations and the negotiation of war and peace. On the other hand, most diplomatic action is highly constrained or invisible. This chapter provides an overview of the ways in which...... and advocacy. It analyzes how professionalization, legalization, personalization and popularization of diplomacy have shaped diplomatic agency including how international law, bureaucracy, public diplomacy and new information technologies have impacted the scope and content of diplomatic agency. Finally...

  16. ¿Entes de regulación o control? Imprecisiones del "moderno" esquema de regulación: reflexiones y enseñanzas del caso argentino Regulatory or control agencies? Impreciseness of the 'modern' regulation scheme: thoughts and teachings from the Argentine case

    Directory of Open Access Journals (Sweden)

    Carolina Nahón

    2007-12-01

    Full Text Available Este artículo analiza las particularidades del "moderno" esquema de regulación de los servicios públicos de infraestructura, que se extendió a partir de los procesos de privatización del último cuarto del siglo XX. Diferenciándose de la arquitectura institucional vigente durante el período de prestación estatal (regulación "endógena", los entes reguladores emergen como el elemento neurálgico de este nuevo esquema. Sin embargo, como se desprende de la experiencia argentina, estos organismos han sido dotados de ambiguas atribuciones regulatorias e inapropiados diseños institucionales, quedando trunca su capacidad real de regulación. A raíz de la difusa delimitación de misiones y funciones e - incluso - frente a las imprecisiones teóricas en la materia, este artículo precisa el alcance de la intervención de los distintos actores del sistema de prestación y regulación: empresas prestadoras, entes reguladores, poderes del Estado (Ejecutivo y Legislativo y usuarios y consumidores. En este sentido, trabaja sobre los diseños institucionales más apropiados para que los entes desarrollen efectivas capacidades de regulación. El análisis se ejemplifica a partir de la experiencia privatizadora argentina - nacional y subnacional - en los servicios de agua potable y saneamiento y distribución de electricidad.This article analyzes the particularities of the public utilities 'modern' regulation scheme, which became predominant during the privatization processes of the last quarter of the twentieth century. In contrast with the institutional framework characteristic of the period of state provision ('endogenous' regulation, the regulatory agencies emerge as the neuralgic element of the new scheme. However, as the Argentine experience demonstrates, these organisms have been endowed with ambiguous regulatory capacities and inappropriate institutional frameworks, and therefore their actual regulatory capacity has been seriously damaged. As

  17. Good Manufacturing Practice-Compliant Production and Lot-Release of Ex Vivo Expanded Regulatory T Cells As Basis for Treatment of Patients with Autoimmune and Inflammatory Disorders

    Directory of Open Access Journals (Sweden)

    Manuel Wiesinger

    2017-10-01

    Full Text Available In recent years, the exploration of regulatory T cell (Treg-based cellular therapy has become an attractive strategy to ameliorate inflammation and autoimmunity in various clinical settings. The main obstacle to the clinical application of Treg in human is their low number circulating in peripheral blood. Therefore, ex vivo expansion is inevitable. Moreover, isolation of Treg bears the risk of concurrent isolation of unwanted effector cells, which may trigger or deteriorate inflammation upon adoptive Treg transfer. Here, we present a protocol for the GMP-compliant production, lot-release and validation of ex vivo expanded Tregs for treatment of patients with autoimmune and inflammatory disorders. In the presented production protocol, large numbers of Treg, previously enriched from a leukapheresis product by using the CliniMACS® system, are ex vivo expanded in the presence of anti-CD3/anti-CD28 expander beads, exogenous IL-2 and rapamycin during 21 days. The expanded Treg drug product passed predefined lot-release criteria. These criteria include (i sterility testing, (ii assessment of Treg phenotype, (iii assessment of non-Treg cellular impurities, (iv confirmation of successful anti-CD3/anti-CD28 expander bead removal after expansion, and (v confirmation of the biological function of the Treg product. Furthermore, the Treg drug product was shown to retain its stability and suppressive function for at least 1 year after freezing and thawing. Also, dilution of the Treg drug product in 0.9% physiological saline did not affect Treg phenotype and Treg function for up to 90 min. These data indicate that these cells are ready to use in a clinical setting in which a cell infusion time of up to 90 min can be expected. The presented production process has recently undergone on site GMP-conform evaluation and received GMP certification from the Bavarian authorities in Germany. This protocol can now be used for Treg-based therapy of various

  18. Regulatory Support of Treatment of Savannah River Site Purex Waste

    International Nuclear Information System (INIS)

    Reid, L.T.

    2009-01-01

    This paper describes the support given by federal and state regulatory agencies to Savannah River Site (SRS) during the treatment of an organic liquid mixed waste from the Plutonium Extraction (Purex) process. The support from these agencies allowed (SRS) to overcome several technical and regulatory barriers and treat the Purex waste such that it met LDR treatment standards. (authors)

  19. 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....

  20. 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....

  1. Lysosomal-associated Transmembrane Protein 4B (LAPTM4B) Decreases Transforming Growth Factor β1 (TGF-β1) Production in Human Regulatory T Cells.

    Science.gov (United States)

    Huygens, Caroline; Liénart, Stéphanie; Dedobbeleer, Olivier; Stockis, Julie; Gauthy, Emilie; Coulie, Pierre G; Lucas, Sophie

    2015-08-14

    Production of active TGF-β1 is one mechanism by which human regulatory T cells (Tregs) suppress immune responses. This production is regulated by glycoprotein A repetitions predominant (GARP), a transmembrane protein present on stimulated Tregs but not on other T lymphocytes (Th and CTLs). GARP forms disulfide bonds with proTGF-β1, favors its cleavage into latent inactive TGF-β1, induces the secretion and surface presentation of GARP·latent TGF-β1 complexes, and is required for activation of the cytokine in Tregs. We explored whether additional Treg-specific protein(s) associated with GARP·TGF-β1 complexes regulate TGF-β1 production in Tregs. We searched for such proteins by yeast two-hybrid assay, using GARP as a bait to screen a human Treg cDNA library. We identified lysosomal-associated transmembrane protein 4B (LAPTM4B), which interacts with GARP in mammalian cells and is expressed at higher levels in Tregs than in Th cells. LAPTM4B decreases cleavage of proTGF-β1, secretion of soluble latent TGF-β1, and surface presentation of GARP·TGF-β1 complexes by Tregs but does not contribute to TGF-β1 activation. Therefore, LAPTM4B binds to GARP and is a negative regulator of TGF-β1 production in human Tregs. It may play a role in the control of immune responses by decreasing Treg immunosuppression. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Growth differentiation factor 9 reverses activin A suppression of steroidogenic acute regulatory protein expression and progesterone production in human granulosa-lutein cells.

    Science.gov (United States)

    Shi, Feng-Tao; Cheung, Anthony P; Klausen, Christian; Huang, He-Feng; Leung, Peter C K

    2010-10-01

    We have reported that growth differentiation factor 9 (GDF9) can enhance activin A (β(A)β(A))-induced inhibin B (αβ(B)) secretion in human granulosa-lutein (hGL) cells, but its effects on steroidogenic acute regulatory protein (StAR), ovarian steroidogenic enzymes, and progesterone production are unknown. We undertook this study to further evaluate GDF9 in this regard. hGL cells from women undergoing in vitro fertilization treatment were cultured with and without small interfering RNA (siRNA) transfection targeted at inhibin α-subunit or GDF9 before treatment with GDF9, activin A, FSH, or combinations. We compared StAR, P450 side-chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase expression in hGL cells and progesterone levels in culture media after these treatments. mRNA, protein, and hormone levels were assessed with real-time RT-PCR, immunoblotting, and ELISA, respectively. Data were analyzed by ANOVA followed by Tukey's test. Activin A alone reduced basal and FSH-induced progesterone production by decreasing the expression of StAR protein, which regulates the rate-limiting step in steroidogenesis but not P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase. GDF9 attenuated these activin A effects on StAR and progesterone. After transfection of α-subunit siRNA, activin A level increased (P progesterone production were attenuated (P progesterone secretion than those observed with activin A treatment alone. GDF9 attenuates the suppressive effects of activin A on StAR expression and progesterone production by increasing the expression of inhibin B, which acts as an activin A competitor.

  3. IL-33 and IgE stimulate mast cell production of IL-2 and regulatory T cell expansion in allergic dermatitis.

    Science.gov (United States)

    Salamon, P; Shefler, I; Moshkovits, I; Munitz, A; Horwitz Klotzman, D; Mekori, Y A; Hershko, A Y

    2017-11-01

    We have previously shown that mast cells (MCs) suppress chronic allergic dermatitis in mice. The underlying mechanism involves MC-derived IL-2, which supports regulatory T cell (Treg) response at the site of inflammation. However, it is not clear what are the factors that drive MCs to produce IL-2. To understand the mechanisms that lead to IL-2 production from MCs in chronic allergic dermatitis. Isolated murine bone marrow-derived MCs (BMMCs) were incubated with various stimulators, and IL-2 production was assessed by RT-PCR and ELISA. The response of signalling pathways was evaluated by MAPK inhibitors and Western blot analysis. The effect of MC-IL-2 on Tregs was studied by incubation of splenic T cells with conditioned media obtained from activated BMMCs. Dermatitis was elicited by repeated exposures of mouse ears to oxazolone. MCs in mouse and human skin samples were evaluated by immunostaining. BMMCs released IL-2 in response to IL-33, and IL-2 production was further enhanced by concomitant FcεRI activation. The effect of IL-33 was mediated by activation of the MAPK family members. IL-2 in conditioned media from IL-33 and IgE-stimulated BMMCs led to considerable expansion of Tregs in vitro. IL-33 levels were elevated in oxazolone-challenged ears along with increased numbers of IL-2-expressing MCs. Human skin with chronic inflammation also contained IL-2-expressing MCs that colocalized with IL-33 staining in the dermis. IL-33, in collaboration with IgE, is critical for MC-IL-2 production in allergic skin disease, thus leading to Treg stimulation and suppression of allergic dermatitis. © 2017 John Wiley & Sons Ltd.

  4. l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

    Science.gov (United States)

    Yu, Hong-Ren; Tsai, Ching-Chang; Chang, Ling-Sai; Huang, Hsin-Chun; Cheng, Hsin-Hsin; Wang, Jiu-Yao; Sheen, Jiunn-Ming; Kuo, Ho-Chang; Hsieh, Kai-Sheng; Huang, Ying-Hsien; Yang, Kuender D.; Hsu, Te-Yao

    2017-01-01

    A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency. PMID:28487700

  5. l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Kuender D. Yang

    2017-04-01

    Full Text Available A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency.

  6. Application of in vitro cell transformation assays in regulatory toxicology for pharmaceuticals, chemicals, food products and cosmetics.

    Science.gov (United States)

    Vanparys, Philippe; Corvi, Raffaella; Aardema, Marilyn J; Gribaldo, Laura; Hayashi, Makoto; Hoffmann, Sebastian; Schechtman, Leonard

    2012-04-11

    Two year rodent bioassays play a key role in the assessment of carcinogenic potential of chemicals to humans. The seventh amendment to the European Cosmetics Directive will ban in 2013 the marketing of cosmetic and personal care products that contain ingredients that have been tested in animal models. Thus 2-year rodent bioassays will not be available for cosmetics/personal care products. Furthermore, for large testing programs like REACH, in vivo carcinogenicity testing is impractical. Alternative ways to carcinogenicity assessment are urgently required. In terms of standardization and validation, the most advanced in vitro tests for carcinogenicity are the cell transformation assays (CTAs). Although CTAs do not mimic the whole carcinogenesis process in vivo, they represent a valuable support in identifying transforming potential of chemicals. CTAs have been shown to detect genotoxic as well as non-genotoxic carcinogens and are helpful in the determination of thresholds for genotoxic and non-genotoxic carcinogens. The extensive review on CTAs by the OECD (OECD (2007) Environmental Health and Safety Publications, Series on Testing and Assessment, No. 31) and the proven within- and between-laboratories reproducibility of the SHE CTAs justifies broader use of these methods to assess carcinogenic potential of chemicals. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Arrests for child pornography production: data at two time points from a national sample of U.S. law enforcement agencies.

    Science.gov (United States)

    Wolak, Janis; Finkelhor, David; Mitchell, Kimberly J; Jones, Lisa M

    2011-08-01

    This study collected information on arrests for child pornography (CP) production at two points (2000-2001 and 2006) from a national sample of more than 2,500 law enforcement agencies. In addition to providing descriptive data about an understudied crime, the authors examined whether trends in arrests suggested increasing CP production, shifts in victim populations, and challenges to law enforcement. Arrests for CP production more than doubled from an estimated 402 in 2000-2001 to an estimated 859 in 2006. Findings suggest the increase was related to increased law enforcement activity rather than to growth in the population of CP producers. Adolescent victims increased, but there was no increase in the proportion of arrest cases involving very young victims or violent images. Producers distributed images in 23% of arrest cases, a proportion that did not change over time. This suggests that much CP production may be primarily for private use. Proactive law enforcement operations increased, as did other features consistent with a robust law enforcement response.

  8. 40 CFR 73.86 - State regulatory autonomy.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false State regulatory autonomy. 73.86 Section 73.86 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... regulatory autonomy. Nothing in this subpart shall preclude a State or State regulatory authority from...

  9. 76 FR 20052 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2011-04-11

    ... the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0187] Notice of Issuance of Regulatory Guide AGENCY... Guide 1.149, ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License...

  10. Hydropower Regulatory and Permitting Information Desktop (RAPID) Toolkit

    Energy Technology Data Exchange (ETDEWEB)

    Levine, Aaron L [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-12-19

    Hydropower Regulatory and Permitting Information Desktop (RAPID) Toolkit presentation from the WPTO FY14-FY16 Peer Review. The toolkit is aimed at regulatory agencies, consultants, project developers, the public, and any other party interested in learning more about the hydropower regulatory process.

  11. Environmental Regulatory Update Table, January/February 1995

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Mayer, S.J.; Salk, M.S.

    1995-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives impacting environmental, health, and safety management responsibilities. the table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  12. 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)

  13. Environmental Regulatory Update Table, January/February 1995

    International Nuclear Information System (INIS)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Mayer, S.J.; Salk, M.S.

    1995-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives impacting environmental, health, and safety management responsibilities. the table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

  14. Monitoring of radioactive ferrous scarp and products, current practices and regulatory problems in North-Eastern Italy

    International Nuclear Information System (INIS)

    Barbina, V.; Bianco, L.

    1997-01-01

    Radioactive scrap metal is a major source of concern among the steel industries of northeastern Italy, since most of the scrap supply comes from east-European countries and may originate from dismantled nuclear installations or dismissed radioactive devices. In this respect reliable monitoring procedures and consistent regulations are essential to face the many economic, legal and safety problems involved in the control and management of radioactive scrap and products. The authors describe the monitoring methods developed in more than two years practice at the steel works Ferriere Nord, Osoppo UD, Italy, as a realistic compromise between reliability, radiation protection and cost. They also discuss the drawbacks sometimes due to the lack of coherent monitoring protocols and exemption levels in Italian regulations, which leave some ways out for the uncontrolled recycling of radioactive metal scrap. (author)

  15. redD and actII-ORF4, Pathway-Specific Regulatory Genes for Antibiotic Production in Streptomyces coelicolor A3(2), Are Transcribed In Vitro by an RNA Polymerase Holoenzyme Containing σhrdD

    NARCIS (Netherlands)

    Fujii, T.; Gramajo, H.C.; Takano, E.; Bibb, M.J.

    1996-01-01

    redD and actII-ORF4, regulatory genes required for synthesis of the antibiotics undecylprodigiosin and actinorhodin by Streptomyces coelicolor A3(2), were transcribed in vitro by an RNA polymerase holoenzyme containing σhrdD. Disruption of hrdD had no effect on antibiotic production, indicating that

  16. The self-antigen, thyroglobulin, induces antigen-experienced CD4+ T cells from healthy donors to proliferate and promote production of the regulatory cytokine, interleukin-10, by monocytes

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Galdiers, Marcel P; Hedegaard, Chris J

    2010-01-01

    . Whereas TT induced pro-inflammatory cytokines [interleukin-2 (IL-2)/interferon-gamma (IFN-gamma)/IL-4/IL-5], TG evoked persistent release of the regulatory IL-10. Some donors, however, also responded with late IFN-gamma production, suggesting that the regulation by IL-10 could be overridden. Although...

  17. 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)

  18. Transformative Agency

    DEFF Research Database (Denmark)

    Majgaard, Klaus

    The purpose of this paper is to enhance the conceptual understanding of the mediatory relationship between paradoxes on an organizational and an individual level. It presents a concept of agency that comprises and mediates between a structural and individual pole. The constitution of this agency ...... is achieved through narrative activity that oscillates between the poles and transforms paradoxes through the configuration of plots and metaphors. Empirical cases are introduced in order to illustrate the implications of this understanding....

  19. Technical support document: Energy conservation standards for consumer products: Dishwashers, clothes washers, and clothes dryers including: Environmental impacts; regulatory impact analysis

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-01

    The Energy Policy and Conservation Act as amended (P.L. 94-163), establishes energy conservation standards for 12 of the 13 types of consumer products specifically covered by the Act. The legislation requires the Department of Energy (DOE) to consider new or amended standards for these and other types of products at specified times. This Technical Support Document presents the methodology, data and results from the analysis of the energy and economic impacts of standards on dishwashers, clothes washers, and clothes dryers. The economic impact analysis is performed in five major areas: An Engineering Analysis, which establishes technical feasibility and product attributes including costs of design options to improve appliance efficiency. A Consumer Analysis at two levels: national aggregate impacts, and impacts on individuals. The national aggregate impacts include forecasts of appliance sales, efficiencies, energy use, and consumer expenditures. The individual impacts are analyzed by Life-Cycle Cost (LCC), Payback Periods, and Cost of Conserved Energy (CCE), which evaluate the savings in operating expenses relative to increases in purchase price; A Manufacturer Analysis, which provides an estimate of manufacturers' response to the proposed standards. Their response is quantified by changes in several measures of financial performance for a firm. An Industry Impact Analysis shows financial and competitive impacts on the appliance industry. A Utility Analysis that measures the impacts of the altered energy-consumption patterns on electric utilities. A Environmental Effects analysis, which estimates changes in emissions of carbon dioxide, sulfur oxides, and nitrogen oxides, due to reduced energy consumption in the home and at the power plant. A Regulatory Impact Analysis collects the results of all the analyses into the net benefits and costs from a national perspective. 47 figs., 171 tabs. (JF)

  20. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production.

    LENUS (Irish Health Repository)

    Lynch, Lydia

    2012-09-21

    Invariant natural killer T (iNKT) cells are evolutionarily conserved innate T cells that influence inflammatory responses. We have shown that iNKT cells, previously thought to be rare in humans, were highly enriched in human and murine adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were depleted, correlating with proinflammatory macrophage infiltration. iNKT cell numbers were restored in mice and humans after weight loss. Mice lacking iNKT cells had enhanced weight gain, larger adipocytes, fatty livers, and insulin resistance on a high-fat diet. Adoptive transfer of iNKT cells into obese mice or in vivo activation of iNKT cells via their lipid ligand, alpha-galactocylceramide, decreased body fat, triglyceride levels, leptin, and fatty liver and improved insulin sensitivity through anti-inflammatory cytokine production by adipose-derived iNKT cells. This finding highlights the potential of iNKT cell-targeted therapies, previously proven to be safe in humans, in the management of obesity and its consequences.

  1. The changing regulatory environment

    International Nuclear Information System (INIS)

    Caron, G.

    1999-01-01

    The role and value of regulation in the energy sector was discussed, demonstrating how, despite common perception, regulation is an essential part of Canada's strategy to find and develop new opportunities. The future vision of regulation for industry participants was presented with particular focus on issues related to streamlining the regulatory process. As far as pipelines are concerned, regulatory actions are necessary to facilitate capacity increases and to ensure the line's integrity, safety and environmental record. Furthermore, regulation provides economic solutions where market forces cannot provide them, as for example where business has elements of monopoly. It arbitrates interests of landowners, business, consumers, and environmental groups. It looks for ways to ensure conditions under which competition can flourish. It acts as the guardian of citizens' rights in a democratic society by providing citizens with an opportunity to be heard on the building or expansion of pipelines and associated facilities. As citizens become more and more concerned about their property and the land that surrounds them, citizen involvement in decision making about how industry activity affects their quality of life will become correspondingly more important. Regulatory agencies are committed to facilitate this engagement by flexible hearing procedures and by making use of evolving communication and information technology

  2. Current regulatory and licensing status for byproduct sources, facilities and applications

    International Nuclear Information System (INIS)

    Tingey, G.L.; Jensen, G.A.; Hazelton, R.F.

    1985-02-01

    Public use of nuclear byproducts, especially radioactive isotopes, will require approval by various regulatory agencies. Use of cesium-137 as an irradiation source for sterilizing medical products will require US Nuclear Regulatory Commission (NRC) approval. Two applications have been filed with NRC, and approval is expected soon. Widespread use of irradiation for food products depends on a favorable ruling by the Food and Drug Administration (FDA). A ruling is pending that would permit irradiation of fruits and vegetables up to 100 krad. NRC also controls the use of isotopes in remote power generators, but little regulatory action has been required in recent years. Recent development of radioluminescent (RL) lighting for runway lights has led to interest by commercial manufacturers. At the present time, a license has been issued to at least one manufacturer for sale of tritium-powered runway lights. 28 refs., 1 fig

  3. Oil and gas exploration and production activities in Brazil: The consideration of environmental issues in the bidding rounds promoted by the National Petroleum Agency

    International Nuclear Information System (INIS)

    Mariano, Jacqueline; La Rovere, Emilio

    2007-01-01

    This paper aims to address and analyze the environmental issues related to the Brazilian bidding rounds for exploration and production of oil and natural gas held by the National Petroleum Agency (ANP) from 1999 to 2005. To do so, after a brief retrospective of the seven rounds, the four main points of the bidding process are analyzed from an environmental perspective: the selection criteria for choosing the areas to be offered, the Minimum Exploration Program required by ANP, the eligibility criteria for the oil companies to take part of the bids and the concession agreements. Thus, it is possible to present the evolution of the environmental component insertion from the first to the seventh bidding round, and then to assess its efficiency in each round, apart from offering suggestions for its improvement. The suggestions presented are based on the related international experience and on the lessons learned during the last seven years

  4. New regulatory landmark for biodiesel use; Novo marco regulatorio para usos de biodiesel

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, Rosangela Moreira de [Agencia Nacional do Petroleo, Gas Natural e Biocombustiveis (ANP), Rio de Janeiro, RJ (Brazil)

    2008-07-01

    The Brazilian Biodiesel Production and Use of Biodiesel - PNPB, made possible the insert of Biodiesel in the Brazilian energy matrix. The National Agency of the Petroleum, Natural Gas and Biofuels - ANP was responsible to create the outline regulatory that established the rules for entrance and commercialization of this new fuel in the country. This work seeks to present the effects of the implantation of the new relative rules to the biodiesel use. (author)

  5. 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

  6. 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

  7. Nuclear energy - some regulatory aspects

    International Nuclear Information System (INIS)

    Jennekens, Jon.

    1980-03-01

    The nuclear industry is often perceived by the public as being uniquely hazardous. As a consequence, the demands placed upon a nuclear regulatory agency invariably include sorting out the valid from the invalid. As the public becomes better informed, more time should become available for regulating the industry. The Canadian nuclear safety philosophy relies upon fundamental principle and basic criteria which licensees must show they are meeting at all stages in the development of a nuclear facility. In reactors, the concept of defence in depth involves the use of well-qualified personnel, compliance with national and international engineering codes and standards, the separation of process and safety systems, frequent testing of safety systems, redundancy in monitoring, control and initiation systems, multiple barriers against fission product release, and strict enforcement of compliance measurements. The Atomic Energy Control Board is writing a set of licensing guides to cover the whole nuclear fuel cycle; however, these will not lead to the impsition of a 'design by regulation' approach in Canada. (LL)

  8. Technical support for the Ohio Clean Coal Technology Program. Volume 2, Baseline of knowledge concerning process modification opportunities, research needs, by-product market potential, and regulatory requirements: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Olfenbuttel, R.; Clark, S.; Helper, E.; Hinchee, R.; Kuntz, C.; Means, J.; Oxley, J.; Paisley, M.; Rogers, C.; Sheppard, W.; Smolak, L. [Battelle, Columbus, OH (United States)

    1989-08-28

    This report was prepared for the Ohio Coal Development Office (OCDO) under Grant Agreement No. CDO/R-88-LR1 and comprises two volumes. Volume 1 presents data on the chemical, physical, and leaching characteristics of by-products from a wide variety of clean coal combustion processes. Volume 2 consists of a discussion of (a) process modification waste minimization opportunities and stabilization considerations; (b) research and development needs and issues relating to clean coal combustion technologies and by-products; (c) the market potential for reusing or recycling by-product materials; and (d) regulatory considerations relating to by-product disposal or reuse.

  9. Starting a hospital-based home health agency: Part II--Key success factors.

    Science.gov (United States)

    Montgomery, P

    1993-09-01

    In Part II of a three-part series, the financial, technological and legislative issues of a hospital-based home health-agency are discussed. Beginning a home healthcare service requires intensive research to answer key environmental and operational questions--need, competition, financial projections, initial start-up costs and the impact of delayed depreciation. Assessments involving technology, staffing, legislative and regulatory issues can help project service volume, productivity and cost-control.

  10. Status report on NRC's current below regulatory concern activities

    International Nuclear Information System (INIS)

    Dragonette, K.S.

    1988-01-01

    The concept of below regulatory concern (BRC) is not new to the Nuclear Regulatory Commission (NRC) or its predecessor agency, the Atomic Energy Commission. The regulations and licensing decisions have involved limited and de facto decisions on BRC since the beginning. For example, consumer products containing radioactive materials have been approved for distribution to persons exempt from licensing for some time and procedures for survey and release of equipment have traditionally been a part of many licensees' radiation safety programs. However, these actions have generally been ad hoc decisions in response to specific needs and have not been necessarily consistent. The need to deal with this regulatory matter has been receiving attention from both Congress and the NRC Commissioners. NRC response has grown from addressing specific waste streams, to generic rulemaking for wastes, and finally to efforts to develop a broad generic BRC policy. Section 10 of the Low-Level Radioactive Waste Policy Amendments Act of 1985 addressed NRC actions on specific waste streams. In response, NRC issued guidance on rulemaking petitions for specific wastes. NRC also issued an advance notice of proposed rulemaking indicating consideration of Commission initiated regulations to address BRC wastes in a generic manner. The Commissioners have directed staff to develop an umbrella policy for all agency decisions concerning levels of risk or dose that do not require government regulation

  11. Effects of vitamin K3 and K5 on proliferation, cytokine production, and regulatory T cell-frequency in human peripheral-blood mononuclear cells.

    Science.gov (United States)

    Hatanaka, Hiroshige; Ishizawa, Hitomi; Nakamura, Yurie; Tadokoro, Hiroko; Tanaka, Sachiko; Onda, Kenji; Sugiyama, Kentaro; Hirano, Toshihiko

    2014-03-18

    The effects of vitamin K (VK) derivatives VK3 and VK5 on human immune cells have not been extensively investigated. We examined the effects of VK3 and VK5 on proliferation, apoptosis, cytokine production, and CD4+CD25+Foxp3+ regulatory T (Treg) cell-frequency in human peripheral blood mononuclear cells (PBMCs) activated by T cell mitogen in vitro. Anti-proliferative effects of VK3 and VK5 on T-cell mitogen activated PBMCs were assessed by WST assay procedures. Apoptotic cells were determined as Annexin V positive/propidium iodide (PI) negative cells. Cytokine concentrations in the supernatant of the culture medium were measured with bead-array procedures followed by analysis with flow cytometry. The CD4+CD25+Foxp3+Treg cells in mitogen-activated PBMCs were stained with fluorescence-labeled specific antibodies followed by flow cytometry. VK3 and VK5 suppressed the mitogen-activated proliferation of PBMCs significantly at 10-100μM (p<0.05). The data also suggest that VK3 and VK5 promote apoptosis in the mitogen-activated T cells. VK3 and VK5 significantly inhibited the production of tumor necrosis factor (TNF) α, interleukin (IL)-4, -6, and -10 from the activated PBMCs at 10-100μM (p<0.05). In contrast, VK3 and VK5 significantly increased Treg cell-frequency in the activated PBMCs at concentrations more than 10μM (p<0.001). Our data suggest that VK3 and VK5 attenuate T cell mediated immunity by inhibiting the proliferative response and inducing apoptosis in activated T cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Independence and the Irish Environmental Protection Agency: A Comparative Assessment

    OpenAIRE

    Shipan, Charles

    2006-01-01

    The Environmental Protection Agency is one of the most prominent regulatory agencies in Ireland. Created in 1992, one of the hallmarks of this agency is its independence from other parts of government. Yet little is known about the actual extent of its independence. Independence and the Irish Environmental Protection Agency: A Comparative Assessment addresses several key questions about the agency's independence. Why was independence such a primary justification for the creation of this a...

  13. Agency Theory

    DEFF Research Database (Denmark)

    Linder, Stefan; Foss, Nicolai Juul

    Agency theory studies the problems and solutions linked to delegation of tasks from principals to agents in the context of conflicting interests between the parties. Beginning from clear assumptions about rationality, contracting and informational conditions, the theory addresses problems of ex...... ante (“hidden characteristics”) as well as ex post information asymmetry (“hidden action”), and examines conditions under which various kinds of incentive instruments and monitoring arrangements can be deployed to minimize the welfare loss. Its clear predictions and broad applicability have allowed...... agency theory to enjoy considerable scientific impact on social science; however, it has also attracted considerable criticism....

  14. Agency Theory

    DEFF Research Database (Denmark)

    Linder, Stefan; Foss, Nicolai Juul

    2015-01-01

    Agency theory studies the problems and solutions linked to delegation of tasks from principals to agents in the context of conflicting interests between the parties. Beginning from clear assumptions about rationality, contracting, and informational conditions, the theory addresses problems of ex...... ante (‘hidden characteristics’) as well as ex post information asymmetry (‘hidden action’), and examines conditions under which various kinds of incentive instruments and monitoring arrangements can be deployed to minimize the welfare loss. Its clear predictions and broad applicability have allowed...... agency theory to enjoy considerable scientific impact on social science; however, it has also attracted considerable criticism....

  15. Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

    Directory of Open Access Journals (Sweden)

    Dipak Dilip Gadade

    2016-12-01

    Full Text Available Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations.

  16. Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development.

    Science.gov (United States)

    Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

    2016-12-01

    Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations.

  17. 78 FR 27971 - Dental Products Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-05-13

    ...] Dental Products Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Dental Products Panel of the Medical Devices Advisory Committee. General Function of the Committee: To... regulatory classification for dental devices known as Endosseous Dental Implants (Blade-form), one of the...

  18. Principles of good regulatory research

    International Nuclear Information System (INIS)

    Rogers, K.

    1991-01-01

    The Commissioner of the US Regulatory Commission addresses several important research-related subjects. The paper describes the Agency philosophy with respect to independence, openness, efficiency, clarity, and reliability; research philosophy with respect to the need for research, the need for quality, and the need for efficiency; research areas with respect to plant aging, human factors, severe accident analysis, advanced reactors, and radioactive waste management; and systems approach to reactor operations, training, licensing, and maintenance

  19. Agency doctorates

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1970-07-01

    Mr. Wen-chuan Li of China has become the first student to obtain a doctor's degree as a result of research work carried out in the Agency. Mr. Li, who is 33, graduated as a Bachelor of Agriculture at Taiwan Provincial Chung-hsing University in 1960 and in 1966 was granted a fellowship to study mutations in plant breeding at the Agency's Seibersdorf Laboratory near Vienna, under the direction of Dr. Knut Mikaelsen, a professor of the University of Bergen. The Hochschule fur Bodenkultur of Vienna accepted the research as being suitable for a thesis and have now granted the degree of Doctor of Agriculture. The subject of the thesis was modifying factors influencing the mutagenic effects of alkylating agents as compared with ionizing radiations in barley. Alkylating agents are involved in the use of chemicals as a means of changing the characteristics of seeds to bring about changes aimed at improving the quality of crops. Mr. Li's work is regarded as a significant contribution to the understanding of the mechanics by which mutations are induced, to the efficient use of chemicals and ionizing radiations in practical applications, and to the efforts of the Agency in collaboration with the Food and Agriculture Organization to benefit food supplies. Mr. Li has now completed his fellowship with the Agency and has been appointed an Assistant Professor in Plant Breeding at Taiwan Provincial Chung-hsing University. The photograph, taken in the plastic hot house at Seibersdorf, shows him studying rice plants grown from seeds subjected to irradiation. Another noteworthy achievement is that of Mr. Karl-Franz Lacina, a security guard at the Agency's headquarters. At the age of 50 he has been accorded the degree of Doctor of Philosophy at Vienna University, the result of six years' work in his leisure time. The major subject was Arabic, with French and philosophy as supporting subject. (author)

  20. Agency doctorates

    International Nuclear Information System (INIS)

    1970-01-01

    Mr. Wen-chuan Li of China has become the first student to obtain a doctor's degree as a result of research work carried out in the Agency. Mr. Li, who is 33, graduated as a Bachelor of Agriculture at Taiwan Provincial Chung-hsing University in 1960 and in 1966 was granted a fellowship to study mutations in plant breeding at the Agency's Seibersdorf Laboratory near Vienna, under the direction of Dr. Knut Mikaelsen, a professor of the University of Bergen. The Hochschule fur Bodenkultur of Vienna accepted the research as being suitable for a thesis and have now granted the degree of Doctor of Agriculture. The subject of the thesis was modifying factors influencing the mutagenic effects of alkylating agents as compared with ionizing radiations in barley. Alkylating agents are involved in the use of chemicals as a means of changing the characteristics of seeds to bring about changes aimed at improving the quality of crops. Mr. Li's work is regarded as a significant contribution to the understanding of the mechanics by which mutations are induced, to the efficient use of chemicals and ionizing radiations in practical applications, and to the efforts of the Agency in collaboration with the Food and Agriculture Organization to benefit food supplies. Mr. Li has now completed his fellowship with the Agency and has been appointed an Assistant Professor in Plant Breeding at Taiwan Provincial Chung-hsing University. The photograph, taken in the plastic hot house at Seibersdorf, shows him studying rice plants grown from seeds subjected to irradiation. Another noteworthy achievement is that of Mr. Karl-Franz Lacina, a security guard at the Agency's headquarters. At the age of 50 he has been accorded the degree of Doctor of Philosophy at Vienna University, the result of six years' work in his leisure time. The major subject was Arabic, with French and philosophy as supporting subject. (author)

  1. 77 FR 8902 - Draft Regulatory Guide: Issuance, Availability Decommissioning of Nuclear Power Reactors

    Science.gov (United States)

    2012-02-15

    ... Decommissioning of Nuclear Power Reactors AGENCY: Nuclear Regulatory Commission. ACTION: Draft regulatory guide... draft regulatory guide (DG) DG-1271 ``Decommissioning of Nuclear Power Reactors.'' This guide describes... Regulatory Guide 1.184, ``Decommissioning of Nuclear Power Reactors,'' dated July 2000. This proposed...

  2. 78 FR 70354 - Conceptual Example of a Proposed Risk Management Regulatory Framework Policy Statement

    Science.gov (United States)

    2013-11-25

    ... NUCLEAR REGULATORY COMMISSION [NRC-2013-0254] Conceptual Example of a Proposed Risk Management Regulatory Framework Policy Statement AGENCY: Nuclear Regulatory Commission. ACTION: Conceptual example of a... ``openness,'' a white paper on a Conceptual Example of a Proposed Risk Management Regulatory Framework (RMRF...

  3. Environmental Compliance for Oil and Gas Exploration and Production

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Christine

    1999-10-26

    The Appalachian/Illinois Basin Directors is a group devoted to increasing communication among the state oil and gas regulatory agencies within the Appalachian and Illinois Basin producing region. The group is comprised of representatives from the oil and gas regulatory agencies from states in the basin (Attachment A). The directors met to discuss regulatory issues common to the area, organize workshops and seminars to meet the training needs of agencies dealing with the uniqueness of their producing region and perform other business pertinent to this area of oil and gas producing states. The emphasis of the coordinated work was a wide range of topics related to environmental compliance for natural gas and oil exploration and production.

  4. Differential effects of Rhodiola rosea on regulatory T cell differentiation and interferon‑γ production in vitro and in vivo.

    Science.gov (United States)

    Xu, Xi; Li, Pingping; Zhang, Peng; Chu, Ming; Liu, Hongju; Chen, Xiaoping; Ge, Qing

    2016-07-01

    Rhodiola rosea (R. rosea), a type of adaptogen, has been previously reported to exhibit immunostimulating activity in rodents and in human peripheral blood mononuclear cells (PBMCs) in vitro. To examine the effect of R. rosea on T cells under simulated microgravity, spaceflight analogs of human head‑down bed rest (HDBR) at ‑6˚ and murine hind limb unloading (HU) were used. A decrease in the levels of interferon‑γ (IFN‑γ) and interleukin‑17 (IL‑17) and an increase in regulatory T (Treg) cells were observed in the placebo group following HDBR. The R. rosea treated HBDR group demonstrated further decreased IFN‑γ production, however, R. rosea exhibited no effect on the ratio of circulating Tregs or Treg cell differentiation. By contrast, the treatment of R. rosea on human T cells in vitro did not alter IFN‑γ secretion, however, Treg differentiation was significantly reduced. An R. rosea‑induced upregulation of hypoxia‑inducible factor 1α (HIF‑1α) contributed to the suppression of Treg differentiation in vitro. Differences in the effect of R. rosea in vitro and in vivo were also observed using a mouse model of microgravity. The results of the current study suggest that R. rosea has differential modulatory effects on T cells in vivo and in vitro and care should be taken when evaluating the effects of R. rosea on the immune system.

  5. Tumor-Associated Macrophages Recruit CCR6+ Regulatory T Cells and Promote the Development of Colorectal Cancer via Enhancing CCL20 Production in Mice

    Science.gov (United States)

    Li, Qun; Zhang, Weiwei; Ke, Fang; Leng, Qibin; Wang, Hong; Chen, Jinfei; Wang, Honglin

    2011-01-01

    Background Tumor-associated macrophages (TAMs) remodel the colorectal cancer (CRC) microenvironment. Yet, findings on the role of TAMs in CRC seem to be contradictory compared with other cancers. FoxP3+ regulatory T (Treg)-cells dominantly infiltrate CRC. However, the underlying molecular mechanism in which TAMs may contribute to the trafficking of Treg-cells to the tumor mass remains unknown. Methodology/Principal Findings CRC was either induced by N-methyl-N-nitrosourea (MNU) and H. pylori or established by subcutaneous injection of mouse colorectal tumor cell line (CMT93) in mice. CMT93 cells were co-cultured with primary macrophages in a transwell apparatus. Recruitment of FoxP3 green fluorescence protein positive (FoxP3GFP+) Treg-cells was assessed using the IVIS Imaging System or immunofluorescence staining. A role for macrophages in trafficking of Treg-cells and in the development of CRC was investigated in CD11b diphtheria toxin receptor (CD11b-DTR) transgenic C57BL/6J mice in which macrophages can be selectively depleted. Treg-cells remarkably infiltrated solid tumor, and predominantly expressed the homing chemokine receptor (CCR) 6 in the induced CRC model. Both CMT93 cancer cells and macrophages produced a large amount of CCL20, the sole ligand of CCR6 in vitro and in vivo. Injection of recombinant mouse CCL20 into tumor sites promoted its development with a marked recruitment of Treg-cells in the graft CRC model. Conditional macrophage ablation decreased CCL20 levels, blocked Treg-cell recruitment and inhibited tumor growth in CD11b-DTR mice grafted with CMT93. Conclusions/Significance TAMs recruit CCR6+ Treg-cells to tumor mass and promote its development via enhancing the production of CCL20 in a CRC mouse model. PMID:21559338

  6. 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.

  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 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...

  8. 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...

  9. 76 FR 13549 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

    Science.gov (United States)

    2011-03-14

    ...'s regulatory program more effective and less burdensome in achieving its regulatory objectives by... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration 15 CFR Chapter IX 50 CFR.... 13563 AGENCY: National Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Request for...

  10. Technology insertion of a COTS RAID server as an image buffer in the image chain of the Defense Mapping Agency's Digital Production System

    Science.gov (United States)

    Mehring, James W.; Thomas, Scott D.

    1995-11-01

    The Data Services Segment of the Defense Mapping Agency's Digital Production System provides a digital archive of imagery source data for use by DMA's cartographic user's. This system was developed in the mid-1980's and is currently undergoing modernization. This paper addresses the modernization of the imagery buffer function that was performed by custom hardware in the baseline system and is being replaced by a RAID Server based on commercial off the shelf (COTS) hardware. The paper briefly describes the baseline DMA image system and the modernization program, that is currently under way. Throughput benchmark measurements were made to make design configuration decisions for a commercial off the shelf (COTS) RAID Server to perform as system image buffer. The test program began with performance measurements of the RAID read and write operations between the RAID arrays and the server CPU for RAID levels 0, 5 and 0+1. Interface throughput measurements were made for the HiPPI interface between the RAID Server and the image archive and processing system as well as the client side interface between a custom interface board that provides the interface between the internal bus of the RAID Server and the Input- Output Processor (IOP) external wideband network currently in place in the DMA system to service client workstations. End to end measurements were taken from the HiPPI interface through the RAID write and read operations to the IOP output interface.

  11. 78 FR 9991 - Agency Information Collection Activities; Information Collection Renewal; Submission for OMB Review

    Science.gov (United States)

    2013-02-12

    ... Capital, Implementation of Basel III, Minimum Regulatory Capital Ratios, Capital Adequacy, Transition... a securitization. The Agencies, on August 30, 2012, proposed three rules (Basel III) that would... Basel III, Minimum Regulatory Capital Ratios, Capital Adequacy, Transition Provisions, and Prompt...

  12. 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

  13. 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

  14. The R2R3-MYB–Like Regulatory Factor EOBI, Acting Downstream of EOBII, Regulates Scent Production by Activating ODO1 and Structural Scent-Related Genes in Petunia[C][W

    Science.gov (United States)

    Spitzer-Rimon, Ben; Farhi, Moran; Albo, Boaz; Cna’ani, Alon; Ben Zvi, Michal Moyal; Masci, Tania; Edelbaum, Orit; Yu, Yixun; Shklarman, Elena; Ovadis, Marianna; Vainstein, Alexander

    2012-01-01

    Flower scent is a highly dynamic trait, under developmental, spatial, and diurnal regulation. The mechanism governing scent production is only beginning to be unraveled. In petunia (Petunia hybrida), EMISSION OF BENZENOIDS II (EOBII) controls transcription of both the shikimate pathway-regulating MYB factor ODORANT1 (ODO1) and phenylpropanoid scent-related structural genes. A promoter-activation screen identified an R2R3-MYB–like regulatory factor of phenylpropanoid volatile biosynthesis acting downstream of EOBII, designated EOBI. EOBI silencing led to downregulation of ODO1 and numerous structural scent-related genes from both the shikimate and phenylpropanoid pathways. The ability of EOBI to directly activate ODO1, as revealed by electrophoretic mobility shift assay and yeast one-hybrid analysis, place EOBI upstream of ODO1 in regulating substrate availability for volatile biosynthesis. Interestingly, ODO1-silenced transgenic petunia flowers accumulated higher EOBI transcript levels than controls, suggesting a complex feedback loop between these regulatory factors. The accumulation pattern of EOBI transcript relative to EOBII and ODO1, and the effect of up/downregulation of EOBII on transcript levels of EOBI and ODO1, further support these factors' hierarchical relationships. The dependence of scent production on EOBI expression and its direct interaction with both regulatory and structural genes provide evidence for EOBI’s wide-ranging involvement in the production of floral volatiles. PMID:23275577

  15. The R2R3-MYB-like regulatory factor EOBI, acting downstream of EOBII, regulates scent production by activating ODO1 and structural scent-related genes in petunia.

    Science.gov (United States)

    Spitzer-Rimon, Ben; Farhi, Moran; Albo, Boaz; Cna'ani, Alon; Ben Zvi, Michal Moyal; Masci, Tania; Edelbaum, Orit; Yu, Yixun; Shklarman, Elena; Ovadis, Marianna; Vainstein, Alexander

    2012-12-01

    Flower scent is a highly dynamic trait, under developmental, spatial, and diurnal regulation. The mechanism governing scent production is only beginning to be unraveled. In petunia (Petunia hybrida), EMISSION OF BENZENOIDS II (EOBII) controls transcription of both the shikimate pathway-regulating MYB factor ODORANT1 (ODO1) and phenylpropanoid scent-related structural genes. A promoter-activation screen identified an R2R3-MYB-like regulatory factor of phenylpropanoid volatile biosynthesis acting downstream of EOBII, designated EOBI. EOBI silencing led to downregulation of ODO1 and numerous structural scent-related genes from both the shikimate and phenylpropanoid pathways. The ability of EOBI to directly activate ODO1, as revealed by electrophoretic mobility shift assay and yeast one-hybrid analysis, place EOBI upstream of ODO1 in regulating substrate availability for volatile biosynthesis. Interestingly, ODO1-silenced transgenic petunia flowers accumulated higher EOBI transcript levels than controls, suggesting a complex feedback loop between these regulatory factors. The accumulation pattern of EOBI transcript relative to EOBII and ODO1, and the effect of up/downregulation of EOBII on transcript levels of EOBI and ODO1, further support these factors' hierarchical relationships. The dependence of scent production on EOBI expression and its direct interaction with both regulatory and structural genes provide evidence for EOBI's wide-ranging involvement in the production of floral volatiles.

  16. Biosimilars: a regulatory perspective from America.

    Science.gov (United States)

    Kay, Jonathan

    2011-05-12

    Biosimilars are protein products that are sufficiently similar to a biopharmaceutical already approved by a regulatory agency. Several biotechnology companies and generic drug manufacturers in Asia and Europe are developing biosimilars of tumor necrosis factor inhibitors and rituximab. A biosimilar etanercept is already being marketed in Colombia and China. In the US, several natural source products and recombinant proteins have been approved as generic drugs under Section 505(b)(2) of the Food, Drug, and Cosmetic Act. However, because the complexity of large biopharmaceuticals makes it difficult to demonstrate that a biosimilar is structurally identical to an already approved biopharmaceutical, this Act does not apply to biosimilars of large biopharmaceuticals. Section 7002 of the Patient Protection and Affordable Care Act of 2010, which is referred to as the Biologics Price Competition and Innovation Act of 2009, amends Section 351 of the Public Health Service Act to create an abbreviated pathway that permits a biosimilar to be evaluated by comparing it with only a single reference biological product. This paper reviews the processes for approval of biosimilars in the US and the European Union and highlights recent changes in federal regulations governing the approval of biosimilars in the US.

  17. How are things going. Obtaining feedback in a regulatory environment

    International Nuclear Information System (INIS)

    McGuire, J.V.; Walsh, M.E.; Boegel, A.J.; Morisseau, D.S.; Persendky, J.J.

    1984-08-01

    This study tested two procedures to gather feedback for a federal agency about its regulatory actions and its licensees' practices. The procedures, a workshop and a mailed survey, targeted a data source new to the agency. Results to date find the feedback workshop useful and the new data source cooperative and valuable. Participation in the workshops is surprising, given their historical backdrop, structure, and psychological literatures. These findings suggest that agencies may be ignoring important data sources for ill-informed reasons. Also, the findings suggest a possible need to restructure existing channels of communication between a regulatory agency and its licensees

  18. 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.)

  19. The text of the agreement of 14 October 1981 between Argentina and the Agency for the application of Safeguards in relation to the heavy water production plant at Arroyito

    International Nuclear Information System (INIS)

    1995-01-01

    The Agreement between the Republic of Argentina, the Federative Republic of Brazil, the Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials and the International Atomic Energy Agency for the Application of Safeguards came into force on 4 March 1994. As a result of the coming into force of the aforesaid Agreement for Argentina, the application of safeguards under the Agreement of 14 October 1981 between Argentina and the IAEA for the application of safeguards in relation to the heavy water production plant at Arroyito has been suspended

  20. Agency doctorates

    International Nuclear Information System (INIS)

    1970-01-01

    Staff members of the Agency working at the Seibersdorf laboratory are continuing to achieve high academic distinction. Two more - both Austrian - have now been awarded the degree of Doctor of Agriculture. Joachim Kramer, who is 26, graduated from the Hochschule fur Bodenkultur in 1967 with the degree of Diplom-Ingenieur and then started work in the plant breeding and genetics section of the laboratory under the direction of Dr. Knut Mikaelsen. The results of the research work he carried out were accepted as the subject of a thesis for which he has now been granted his doctorate. The doctoral promotion took place on 30 June, at a ceremony attended by Dr. Andre Finkelstein, Deputy Director General for Research and Isotopes. The subject of Dr. Kramer's thesis was a comprehensive study of the mutagenic effects of fast neutrons and gamma rays, and the influence of various modifying factors such as water content, oxygen and metabolic state of seeds at the time of irradiation. This work has contributed significantly to the understanding of the mechanisms by which these two types of ionizing radiation produce mutations in seeds. The knowledge gained will be of great importance in the efficient use of ionizing radiation in practical plant breeding. Paul Wassermann, who is 33 years old, joined the Agency in 1965. He, too, graduated from the Hochschule fur Bodenkultur as Diplom-Ingenieur in agriculture, having graduated with honours previously from the agricultural secondary school at Raumberg, Austria, in 1958. Dr. Wassermann's own words may be used to explain how he came to gain his doctorate. 'In October, 1966, I completed my studies at the Hochschule,' he writes. 'I was employed at the Agency laboratories in Seibersdorf, working in the plant and soils group. Encouraged by the interesting research which was performed there, a thesis entitled 'the Fate of Nitrogen in Submerged Rice Soils' was started, which finally led to the doctor's degree in Agriculture in June this year

  1. 77 FR 61592 - Arkansas Electric Cooperative Corporation; Mississippi Delta Energy Agency; Clarksdale Public...

    Science.gov (United States)

    2012-10-10

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL12-110-000] Arkansas Electric Cooperative Corporation; Mississippi Delta Energy Agency; Clarksdale Public Utilities Commission.... 825(h), Arkansas Electric Cooperative Corporation, Mississippi Delta Energy Agency, and its two...

  2. The European Medicines Agency's strategies to meet the challenges of Alzheimer disease.

    Science.gov (United States)

    Haas, Manuel; Mantua, Valentina; Haberkamp, Marion; Pani, Luca; Isaac, Maria; Butlen-Ducuing, Florence; Vamvakas, Spiros; Broich, Karl

    2015-04-01

    Regulatory agencies have a key role in facilitating the development of new drugs for Alzheimer disease, particularly given the challenges associated with early intervention. Here, we highlight the strategies of the European Medicines Agency to help address such challenges.

  3. 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)

  4. Development of the Regulatory Framework in Mexico

    International Nuclear Information System (INIS)

    Carreño Padilla, A. L.; Paz García Beltran, A.B.; Godínez Sánchez, V.

    2015-01-01

    The present study describes and introduces in a simplified way the process for issuing a Mexican Official Standard of Nuclear series, setting out the departments and agencies involved in this process, and also describing the main challenges identified for preparation, issuance and review of them. Furthermore, topics that are currently in the process of standardisation in Mexico in radiation and nuclear safety are mentioned. The National Commission for Nuclear Safety and Safeguards is the regulatory body empowered and commissioned in Mexico to issue and amends the Official Mexican Standards in nuclear and radiation safety, whose duties and responsibilities are set out in the Regulatory Law on Nuclear Matters of Article 27. The Mexican Standards are of social kind because they are focused to prevent risks that could affect human been health, animal or plants damages, and are also associated to safety in the workplaces, to avoid damages which may be irreparable to the environment and population. Normalization is the process by which all the activities concerning public health, environment protection, labor protection, among others, are ruled on in both, private and public sectors. Through this process, the rules, features or products specifications are set for a product or a regulated service. The objective of a standard is to get an optimum degree of order in a given activity. The objective of creating a regulation is to develop legal certainty, to avoid imminent harm or to reduce existing damages on health, the environment and the Economy. Currently, the regulation for nuclear and radiological safety, physical security, as well as for safeguards in Mexico, is under constant development, looking for to cover the safety needs of employees, licencees, environment and society in a whole; many of these needs are supported by the international recommendations of the IAEA. (author)

  5. 78 FR 34386 - Agency Forms Undergoing Paperwork Act Review

    Science.gov (United States)

    2013-06-07

    ... representatives in state regulatory agencies in the 50 states and the District of Columbia primarily via telephone.... Nursing homes and skilled nursing facilities are also excluded, unless they have a unit or wing meeting...

  6. 76 FR 76413 - Agency Forms Undergoing Paperwork Reduction Act Review

    Science.gov (United States)

    2011-12-07

    ... representatives in state regulatory agencies in the 50 states and the District of Columbia primarily via telephone... exclusively are excluded. Nursing homes and skilled nursing facilities are also excluded, unless they have a...

  7. OECD Nuclear Energy Agency. 5 activity report. 1976

    International Nuclear Information System (INIS)

    1977-01-01

    The main activities of the Agency are reviewed: nuclear power trends; regulatory aspects of nuclear power; technical developments: Eurochemic, Halden, Dragon, food irradiation; gas-cooled fast reactors, isotopic batteries; nuclear data Centers

  8. OECD Nuclear Energy Agency. 3. Activity report, 1974

    International Nuclear Information System (INIS)

    1975-01-01

    The main activities of the Agency are reviewed: study of nuclear power trends; regulatory aspects of nuclear power; technical developments: Eurochemic, Halden, Dragon, food irradiation, gas-cooled fast reactors, direct conversion, isotopic batteries; nuclear energy information

  9. Regulatory Acceptance of Alternative Methods in the Development and Approval of Pharmaceuticals.

    Science.gov (United States)

    Beken, Sonja; Kasper, Peter; van der Laan, Jan-Willem

    Animal studies may be carried out to support first administration of a new medicinal product to either humans or the target animal species, or before performing clinical trials in even larger populations, or before marketing authorisation, or to control quality during production. Ethical and animal welfare considerations require that animal use is limited as much as possible. Directive 2010/63/EU on the protection of animals used for scientific purposes unambiguously fosters the application of the principle of the 3Rs when considering the choice of methods to be used.As such, today, the 3Rs are embedded in the relevant regulatory guidance both at the European (European Medicines Agency (EMA)) and (Veterinary) International Conference on Harmonization ((V)ICH) levels. With respect to non-clinical testing requirements for human medicinal products, reduction and replacement of animal testing has been achieved by the regulatory acceptance of new in vitro methods, either as pivotal, supportive or exploratory mechanistic studies. Whilst replacement of animal studies remains the ultimate goal, approaches aimed at reducing or refining animal studies have also been routinely implemented in regulatory guidelines, where applicable. The chapter provides an overview of the implementation of 3Rs in the drafting of non-clinical testing guidelines for human medicinal products at the level of the ICH. In addition, the revision of the ICH S2 guideline on genotoxicity testing and data interpretation for pharmaceuticals intended for human use is discussed as a case study.In October 2010, the EMA established a Joint ad hoc Expert Group (JEG 3Rs) with the mandate to improve and foster the application of 3Rs principles to the regulatory testing of medicinal products throughout their lifecycle. As such, a Guideline on regulatory acceptance of 3R testing approaches was drafted that defines regulatory acceptance and provides guidance on the scientific and technical criteria for regulatory

  10. Regulatory perspectives of concept assessment

    International Nuclear Information System (INIS)

    Flavelle, Peter A.

    1987-09-01

    The Atomic Energy Control Board is the head agency for the regulatory review of the Assessment of the Canadian Concept for Nuclear Fuel Waste Disposal being done by Atomic Energy of Canada Limited and Ontario Hydro. This paper describes the regulatory perspective of how the Concept Assessment could demonstrate the feasibility of a disposal conforming to regulatory requirements. The long-term aspects of Concept Assessment encourage the use of various predictive techniques for different time scales. Each technique will have a different potential for establishing confidence in the predictions. The predicted performance of a facility during operation should have a very high confidence, as it can be based on standard engineering calculations and the predictions can be validated later by monitoring during operation. The predictions of the transient period following closure of the facility should achieve a medium level of confidence, since they can be based on extrapolations of predictions of operational performance, using models that can be calibrated with monitoring data and with averaged input data derived from natural analog studies. Predictions based on fundamental processes will have a medium level of confidence when made to intermediate times after closure. Long-term predictions using generic or typical input data or Monte Carlo calculations of simplified models will have the least confidence and yet they can still contribute to the confidence that the disposal concept will conform to regulatory requirements

  11. Monitoring Quality of Biotherapeutic Products Using Multivariate Data Analysis.

    Science.gov (United States)

    Rathore, Anurag S; Pathak, Mili; Jain, Renu; Jadaun, Gaurav Pratap Singh

    2016-07-01

    Monitoring the quality of pharmaceutical products is a global challenge, heightened by the implications of letting subquality drugs come to the market on public safety. Regulatory agencies do their due diligence at the time of approval as per their prescribed regulations. However, product quality needs to be monitored post-approval as well to ensure patient safety throughout the product life cycle. This is particularly complicated for biotechnology-based therapeutics where seemingly minor changes in process and/or raw material attributes have been shown to have a significant effect on clinical safety and efficacy of the product. This article provides a perspective on the topic of monitoring the quality of biotech therapeutics. In the backdrop of challenges faced by the regulatory agencies, the potential use of multivariate data analysis as a tool for effective monitoring has been proposed. Case studies using data from several insulin biosimilars have been used to illustrate the key concepts.

  12. 77 FR 7968 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2012-02-13

    ... Regulation Sequence No. Title Identifier No. 392 Non-Federal Oil and Gas 1024-AD78 Rights. National Park.... Timetable: Action Date FR Cite NPRM 07/00/12 Regulatory Flexibility Analysis Required: Yes. Agency Contact... anaconda, and Beni anaconda. Timetable: Action Date FR Cite ANPRM 01/31/08 73 FR 5784 ANPRM Comment Period...

  13. 78 FR 1570 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2013-01-08

    ... Deregulatory Priorities. Gregory H. Woods, General Counsel. Energy Efficiency and Renewable Energy--Proposed... Action 10/01/12 77 FR 59719 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Stephen Witkowski, Phone: 202 586-7463, Email: stephen[email protected] . RIN: 1904-AB90 [FR Doc. 2012-31497...

  14. 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...

  15. 76 FR 18457 - Regulatory Review Schedule; Tribal Consultation

    Science.gov (United States)

    2011-04-04

    ... that the NIGC provide tribal gaming commissions access to licensing information via an online database... DEPARTMENT OF THE INTERIOR National Indian Gaming Commission 25 CFR Chapter III Regulatory Review Schedule; Tribal Consultation AGENCY: National Indian Gaming Commission. ACTION: Notice of Regulatory...

  16. 76 FR 411 - Regulatory Guidance Concerning Electronic Signatures and Documents

    Science.gov (United States)

    2011-01-04

    ... guidance, including memoranda and letters, may no longer be relied upon to the extent they are inconsistent... Concerning Electronic Signatures and Documents AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of regulatory guidance. SUMMARY: FMCSA issues regulatory guidance concerning the...

  17. 76 FR 7762 - Drinking Water: Regulatory Determination on Perchlorate

    Science.gov (United States)

    2011-02-11

    ...-9262-8] RIN 2040-AF08 Drinking Water: Regulatory Determination on Perchlorate AGENCY: Environmental...'s) regulatory determination for perchlorate in accordance with the Safe Drinking Water Act (SDWA... substantial likelihood that perchlorate will occur in public water systems with a frequency and at levels of...

  18. Environmental Regulatory Update Table, November--December 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1994-01-01

    The Environmental Regulatory Update Table provides information on regulatory of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  19. Environmental regulatory update table November--December 1994

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Mayer, S.J.; Salk, M.S.

    1995-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  20. Environmental Regulatory Update Table, January--February 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  1. Environmental sciences division: Environmental regulatory update table July 1988

    International Nuclear Information System (INIS)

    Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1988-08-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

  2. Environmental Regulatory Update Table, May--June 1994

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Salk, M.S.

    1994-07-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  3. Environmental Regulatory Update Table, May/June 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-07-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  4. Environmental regulatory update table, March--April 1994

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E. [Oak Ridge National Lab., TN (United States). Health Sciences Research Div.; Salk, M.S. [Oak Ridge National Lab., TN (United States). Environmental Sciences Div.

    1994-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  5. Environmental Regulatory Update Table July/August 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-09-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  6. Environmental Regulatory Update Table, March/April 1993. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-05-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  7. Environmental Regulatory Update Table, March/April 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-05-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  8. Environmental Regulatory Update Table, January/February 1992

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1992-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action. This table is for January/February 1992.

  9. Environmental Regulatory Update Table, November--December 1992

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.; Salk, M.S.

    1993-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly wit information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  10. Environmental Regulatory Update Table, July--August 1992

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.; Salk, M.S.

    1992-09-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  11. Environmental Regulatory Update Table, September/October 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-11-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operation and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  12. Environmental Regulatory Update Table, January--February 1994

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1994-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations ad contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  13. Environmental regulatory update table, September--October 1992

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.; Salk, M.S.

    1992-11-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  14. Environmental regulatory update table, July/August 1994

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Salk, M.S.

    1994-09-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  15. Environmental Regulatory Update Table, March/April 1992

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1992-05-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  16. Environmental regulatory update table, July/August 1994

    International Nuclear Information System (INIS)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Salk, M.S.

    1994-09-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action

  17. 78 FR 39284 - Technical Guidance for Assessing Environmental Justice in Regulatory Analysis

    Science.gov (United States)

    2013-07-01

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OA-2013-0320; FRL-9830-1] Technical Guidance for Assessing Environmental Justice in Regulatory Analysis AGENCY: Environmental Protection Agency (EPA). ACTION: Notice... Environmental Protection Agency (EPA) issued for public comment a document entitled, ``Technical Guidance for...

  18. Regulatory aspects of mixed waste

    International Nuclear Information System (INIS)

    Boyle, R.R.; Orlando, D.A.

    1990-01-01

    Mixed waste is waste that satisfies the definition of low-level radioactive waste in the Low-Level Radioactive Waste Policy Amendments Act of 1985 (LLRWPAA) and contains hazardous waste that is either: (1) listed as a hazardous waste in 40 CFR 261, Subpart D; or (2) causes the waste to exhibit any of the characteristics identified in 40 CFR 261, Subpart C. Low-level radioactive waste is defined in the LLRWPAA as radioactive material that is not high level waste, spent nuclear fuel, or byproduct material, as defined in Section 11e(2) of the Atomic Energy Act of 1954, and is classified as low-level waste by the U.S. Nuclear Regulatory Commission (NRC). This paper discusses dual regulatory (NRC and Environmental Protection Agency) responsibility, overview of joint NRC/EPA guidance, workshops, national mixed waste survey, and principal mixed waste uncertainties

  19. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2013-01-01

    - International co-operation: Law ratifying the agreement between the International Atomic Energy Agency and Greece in the area of education and training; - Nuclear safety and radiological protection: Ministerial decision establishing requirements for nuclear safety and regulatory control of research reactors; Moldova - General legislation: New comprehensive law governing nuclear and radiological activities; United States - Issuance of the 'Strategy for the Management and Disposal of Used Nuclear Fuel and High-Level Radioactive Waste'; - Ongoing activities: The Blue Ribbon Commission noted the need for near-term actions that can lay the groundwork for the next generation of nuclear waste policies and programmes included in its recommendations; - Physical protection of by-product material final rulemaking: On 19 March 2013, the NRC published a final rule amending its regulations to establish security requirements for the use and transport of category 1 and category 2 quantities of radioactive material; - Update on the NRC's response to the events at the Fukushima Daiichi nuclear site regarding filtered vents and consideration of economic consequences

  20. Controlling Methane Emissions in the Natural Gas Sector. A Review of Federal and State Regulatory Frameworks Governing Production, Gathering, Processing, Transmission, and Distribution

    Energy Technology Data Exchange (ETDEWEB)

    Paranhos, Elizabeth [Energy Innovation Partners, Seoul (South Korea); Kozak, Tracy G. [Energy Innovation Partners, Seoul (South Korea); Boyd, William [Univ. of Colorado, Boulder, CO (United States); Bradbury, James [U.S. Department of Energy, Washington, DC (United States); Steinberg, D. C. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Arent, D. J. [Joint Inst. for Strategic Energy Alaysis, Washington, DC (United States)

    2015-04-23

    This report provides an overview of the regulatory frameworks governing natural gas supply chain infrastructure siting, construction, operation, and maintenance. Information was drawn from a number of sources, including published analyses, government reports, in addition to relevant statutes, court decisions and regulatory language, as needed. The scope includes all onshore facilities that contribute to methane emissions from the natural gas sector, focusing on three areas of state and federal regulations: (1) natural gas pipeline infrastructure siting and transportation service (including gathering, transmission, and distribution pipelines), (2) natural gas pipeline safety, and (3) air emissions associated with the natural gas supply chain. In addition, the report identifies the incentives under current regulatory frameworks to invest in measures to reduce leakage, as well as the barriers facing investment in infrastructure improvement to reduce leakage. Policy recommendations regarding how federal or state authorities could regulate methane emissions are not provided; rather, existing frameworks are identified and some of the options for modifying existing regulations or adopting new regulations to reduce methane leakage are discussed.

  1. 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)

  2. 77 FR 70741 - Agency Information Collection Extension

    Science.gov (United States)

    2012-11-27

    ... Management and Budget (OMB) to revise a currently-approved data collection under the provisions of the... analysis tools for federal/state agencies, AFV suppliers, vehicle fleet managers, and other interested... sent to the: DOE Desk Officer, Office of Information and Regulatory Affairs, Office of Management and...

  3. Validation of a standard field test method in four countries to assess the toxicity of residues in dung of cattle treated with veterinary medical products

    NARCIS (Netherlands)

    Floate, Kevin D.; Düring, Rolf Alexander; Hanafi, Jamal; Jud, Priska; Lahr, Joost; Lumaret, Jean Pierre; Scheffczyk, Adam; Tixier, Thomas; Wohde, Manuel; Römbke, Jörg; Sautot, Lucille; Blanckenhorn, Wolf U.

    2016-01-01

    Registration of veterinary medical products includes the provision that field tests may be required to assess potential nontarget effects associated with the excretion of product residues in dung of treated livestock (phase II, tier B testing). However, regulatory agencies provide no guidance on

  4. Benefit-Risk Assessment, Communication, and Evaluation (BRACE) throughout the life cycle of therapeutic products : overall perspective and role of the pharmacoepidemiologist

    NARCIS (Netherlands)

    Radawski, Christine; Morrato, Elaine; Hornbuckle, Kenneth; Bahri, Priya; Smith, Meredith; Juhaeri, Juhaeri; Mol, Peter; Levitan, Bennett; Huang, Han-Yao; Coplan, Paul; Li, Hu

    2015-01-01

    Purpose Optimizing a therapeutic product's benefit-risk profile is an on-going process throughout the product's life cycle. Different, yet related, benefit-risk assessment strategies and frameworks are being developed by various regulatory agencies, industry groups, and stakeholders. This paper

  5. 77 FR 70846 - Regulatory Guide 1.182, “Assessing and Managing Risk Before Maintenance Activities at Nuclear...

    Science.gov (United States)

    2012-11-27

    ... NUCLEAR REGULATORY COMMISSION [NRC-2012-0285] Regulatory Guide 1.182, ``Assessing and Managing Risk Before Maintenance Activities at Nuclear Power Plants'' AGENCY: Nuclear Regulatory Commission... withdrawing Regulatory Guide (RG)1.182, Revision (Rev.) 0, ``Assessing and Managing Risk Before Maintenance...

  6. The self-antigen, thyroglobulin, induces antigen-experienced CD4+ T cells from healthy donors to proliferate and promote production of the regulatory cytokine, interleukin-10, by monocytes

    DEFF Research Database (Denmark)

    Nielsen, Claus Kim Hostein; Galdiers, Marcel P; Hedegaard, Chris Juul

    2010-01-01

    Thyroglobulin (TG), as autoantigen, induces in vitro proliferation of T and B cells from normal individuals, but the cytokine production differs from that in patients with autoimmune thyroid disease. Here, we investigate whether normal T cells responding to TG are naive, or have previously....... Whereas TT induced pro-inflammatory cytokines [interleukin-2 (IL-2)/interferon-gamma (IFN-gamma)/IL-4/IL-5], TG evoked persistent release of the regulatory IL-10. Some donors, however, also responded with late IFN-gamma production, suggesting that the regulation by IL-10 could be overridden. Although...... monocytes were prime producers of IL-10 in the early TG response, a few IL-10-secreting CD4(+) T cells, primarily with CD45RO(+) memory phenotype, were also detected. Furthermore, T-cell depletion from the mononuclear cell preparation abrogated monocyte IL-10 production. Our findings indicate active...

  7. The Independence of Vietnam Regulatory Body

    International Nuclear Information System (INIS)

    Nguyen, Hoang Anh; Choi, Kwang Sik

    2011-01-01

    In the field of peaceful purposes, the activity of nuclear agencies is often divided into 2 systems: the nuclear application system and the safety system. Depending on the magnitude of atomic energy application development, the responsibility of the safety system was assigned to a few agencies in each country. In Vietnam, the nuclear safety responsibility is assigned primarily to the radiation and nuclear safety agency. However, the provisions of the normative system of law prevailing in other sectors such as investment, construction, electricity or environmental protection, many agencies are responsible for ensuring safety in each sector, leading to a conflict of interest among those agencies. This is the weakness in the management system of Vietnam compared to other countries with nuclear power development. The purpose of this paper is to analyze the state of Vietnam's legal framework in nuclear safety regulation and its dependence of regulatory body aspects and promoting the way to overcome it

  8. 76 FR 13000 - Transfer of Commercial First-Class Mail Parcels to Competitive Product List

    Science.gov (United States)

    2011-03-09

    ...: On February 24, 2011, the United States Postal Service[supreg] filed with the Postal Regulatory Commission a Request of the United States Postal Service to transfer commercial First-Class Mail Parcels from... POSTAL SERVICE Transfer of Commercial First-Class Mail Parcels to Competitive Product List AGENCY...

  9. 75 FR 52378 - Transfer of Commercial Standard Mail Parcels to Competitive Product List

    Science.gov (United States)

    2010-08-25

    ..., 2010, the United States Postal Service[reg] filed with the Postal Regulatory Commission a Request of the United States Postal Service to transfer commercial Standard Mail Parcels from the Mail... POSTAL SERVICE Transfer of Commercial Standard Mail Parcels to Competitive Product List AGENCY...

  10. 77 FR 28410 - Product Change-Parcel Select Negotiated Service Agreement

    Science.gov (United States)

    2012-05-14

    ... filed with the Postal Regulatory Commission a Request of the United States Postal Service to Add Parcel... POSTAL SERVICE Product Change--Parcel Select Negotiated Service Agreement AGENCY: Postal Service\\TM\\. ACTION: Notice. SUMMARY: The Postal Service gives notice of filing a request with the Postal...

  11. 75 FR 74755 - Product Change-Parcel Return Service Negotiated Service Agreement

    Science.gov (United States)

    2010-12-01

    ... POSTAL SERVICE Product Change--Parcel Return Service Negotiated Service Agreement AGENCY: Postal.... SUPPLEMENTARY INFORMATION: The United States Postal Service[supreg] hereby gives notice that on November 17, 2010, it filed with the Postal Regulatory Commission a Request of the United States Postal Service to...

  12. 76 FR 396 - Product Change-Priority Mail-Non-Published Rates

    Science.gov (United States)

    2011-01-04

    ... POSTAL SERVICE Product Change--Priority Mail--Non-Published Rates AGENCY: Postal Service TM . ACTION: Notice. SUMMARY: Postal Service notice of filing of a request with the Postal Regulatory... States Postal Service Concerning Priority Mail--Non-Published Rates and Notice of Filing Materials Under...

  13. Schedules for Regulatory Regimes

    International Nuclear Information System (INIS)

    Austvik, Ole Gunnar

    2003-01-01

    The idea of regulating transporters' terms of operations is that if the market itself does not produce optimal outcomes, then it can be mimicked to do so through regulatory and other public instruments. The first-best solution could be a subsidized (publicly owned) enterprise that sets tariffs according to marginal costs. This has been the tradition in many European countries in the aftermath of WW2. Due to lack of innovative pressure on and x-inefficiency in these companies, this solution is today viewed as inferior to the system of regulating independent (privately owned) firms. When the European gas market becomes liberalized, part of the process in many countries is to (partially) privatise the transport utilities. Privatised or not, in a liberalized market, the transport utilities should face an independent authority that overviews their operations not only in technical, but also in economic terms. Under regulation, a ''visible hand'' is introduced to correct the imperfect market's ''invisible hand''. By regulating the framework and conditions for how firms may operate, public authorities seek to achieve what is considered optimal for the society. The incentives and disincentives given for pricing and production should create mechanisms leading to an efficient allocation of resources and ''acceptable'' distribution of income. As part of intervening into firms' behavior, regulation may be introduced to direct the firm to behave in certain ways. The framework and regulatory mechanisms for the market must then be constructed in a way that companies voluntarily produce an amount at a price that gives maximal profits and simultaneously satisfies social goals. The regulations should lead to consistency between the company's desire to maximize profits and the society's desire for maximizing welfare, as in a perfectly competitive market. This is the core of regulatory economics

  14. 78 FR 54517 - Water Quality Standards Regulatory Clarifications

    Science.gov (United States)

    2013-09-04

    ... 131 Water Quality Standards Regulatory Clarifications; Proposed Rule #0;#0;Federal Register / Vol. 78... AGENCY 40 CFR Part 131 [EPA-HQ-OW-2010-0606; FRL-9839-7] RIN 2040-AF 16 Water Quality Standards... Environmental Protection Agency (EPA) is proposing changes to the federal water quality standards (WQS...

  15. 76 FR 61402 - Draft Nuclear Regulatory Commission Fiscal Year 2012-2016 Strategic Plan

    Science.gov (United States)

    2011-10-04

    ...-2016 Strategic Plan AGENCY: Nuclear Regulatory Commission. ACTION: Draft NUREG; request for comment... comment on draft NUREG-1614, Volume 5. ``U.S. Nuclear Regulatory Commission, FY 2012-2016 Strategic Plan,'' dated September 2011. The NRC's draft FY 2012-2016 strategic plan describes the agency's mission and...

  16. 77 FR 15142 - Updated Nuclear Regulatory Commission Fiscal Years 2008-2013 Strategic Plan

    Science.gov (United States)

    2012-03-14

    ... 2008-2013 Strategic Plan AGENCY: Nuclear Regulatory Commission. ACTION: Strategic plan. SUMMARY: The U...-1614, Volume 5, ``U.S. Nuclear Regulatory Commission, Fiscal Years [FY] 2008-2013 Strategic Plan,'' dated February 2012. The updated FY 2008-2013 strategic plan describes the agency's mission and...

  17. 75 FR 61485 - Regulatory Training Session With Air Carriers, EPA Regional Partners and Other Interested Parties...

    Science.gov (United States)

    2010-10-05

    ... ENVIRONMENTAL PROTECTION AGENCY [FRL-9210-6] Regulatory Training Session With Air Carriers, EPA... Agency (EPA) will hold a two-day training session on the regulatory requirements of the Aircraft Drinking... session will be provided in early 2011. ADDRESSES: The training will be held at the Rosslyn Holiday Inn at...

  18. Regulatory challenges

    International Nuclear Information System (INIS)

    Austvik, Ole Gunnar

    2003-01-01

    The problem for policy makers wanting to liberalize natural gas markets is that its concentrated structure may also be the socially most efficient one. Because of scale economies, more firms operating in the market may incur higher transportation costs unless the market grows sufficiently in each geographic segment. This argument goes for product extension through vertical (or horizontal) integration and the exploitation of economies of scope as well. Thus, the challenge for governments is to intervene in a way that preserves a market structure that has the potential to minimize cost, and at the same lime change its behavior in order to avoid possible lax cost control and exploitation of market power. The existence of scope advantages indicates that liberalization of the market should open for the possibility to bundle services in competition with provision of unbundled services. If operations are unbundled and there exist economies of scope, the gain from increased competition should be weighed against the losses of less efficient operations of each firm. Thus, with the growth in the European market, gradually more arguments support the idea of unbundling. The significant scale economy in trunk pipelines, sunk investments and capital immobility, possible economies of scope in vertical integration and companies' bundling of services influences vertical and horizontal ownership relations and contractual terms in the European gas market. In specific segments of the markets, these relationships may promote efficient investments and pricing without public interference, but the strong concentration of market power indicates that this is rather the exception than the rule. In order to design an efficient and welfare maximizing way of regulating the market one needs a closer identification of the actual goal of the regulation. Microeconomic theory is often used for this purpose. The author discusses the alternatives of laissez-faire, nationalization or regulation for the

  19. Existing Regulatory Approaches to Reducing Exposures to Chemical- and Product-Based Risk and Their Applicability to Diet-Related Chronic Disease.

    Science.gov (United States)

    Cohen, Deborah A; Knopman, Debra S

    2018-04-17

    We aimed to identify and categorize the types of policies that have been adopted to protect Americans from harmful exposures that could also be relevant for addressing diet-related chronic diseases. This article examines and categorizes the rationales behind government regulation. Our interest in the historical analysis is to inform judgments about how best to address newly emergent risks involving diet-related chronic disease within existing regulatory and information-based frameworks. We assessed exemplars of regulation with respect to harmful exposures from air, water, and food, as well as regulations that are intended to modify voluntary behaviors. Following the comparative analysis, we explored how exposures that lead to diet-related chronic diseases among the general population fit within models of regulation adopted for other comparable risks. We identified five rationales and five approaches that protect people from harmful exposures. Reasons for regulation include: protection from involuntary exposure to risk, high risk of death or chronic illness, ubiquity of risk, counteraction to limit compulsive behaviors, and promotion of population health. Regulatory approaches include: mandatory limits on use, mandatory limits on exposure, mandatory controls on quality, mandatory labeling, and voluntary guidance. In contrast to the use of mandates, the prevention of diet-related chronic diseases thus far has largely relied on information-only approaches and voluntary adoption of guidelines. There is ample precedent for mandatory regulatory approaches that could address harms related to exposure to unhealthy diets, but several barriers to action would need to be overcome. © 2018 Society for Risk Analysis.

  20. CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin-10 production predominantly by regulatory B cells

    DEFF Research Database (Denmark)

    Fjelbye, Jonas; Antvorskov, Julie C; Buschard, Karsten

    2015-01-01

    .05) and peritoneal cavity (80.8% decrease; P challenge, which suggests an important regulatory and protective role of CD1d-dependent NKT cells in CHS in our model, at least in part via regulation of IL-10 producing B(regs) ....... knockout (CD1d KO) and wild-type (Wt) mice after contact allergen exposure. For induction of CHS, C57BL/6 CD1d KO mice (n = 6) and C57BL/6 Wt mice (n = 6) were sensitised with 1% (w/v) dinitrochlorobenzene (DNCB) or vehicle for three consecutive days and subsequently challenged with a single dose of 0...