77 FR 71803 - Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products...

Science.gov (United States)

2012-12-04

... PET Drug Products--Questions and Answers.'' This guidance provides questions and answers that address.... 2201, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in... availability of a guidance entitled ``FDA Oversight of PET Drug Products--Questions and Answers.'' In 1997...

Hospital board oversight of quality and safety: a stakeholder analysis exploring the role of trust and intelligence.

Science.gov (United States)

Millar, Ross; Freeman, Tim; Mannion, Russell

2015-06-16

Hospital boards, those executive members charged with developing appropriate organisational strategies and cultures, have an important role to play in safeguarding the care provided by their organisation. However, recent concerns have been raised over boards' ability to enact their duty to ensure the quality and safety of care. This paper offers critical reflection on the relationship between hospital board oversight and patient safety. In doing so it highlights new perspectives and suggestions for developing this area of study. The article draws on 10 interviews with key informants and policy actors who form part of the 'issue network' interested in the promotion of patient safety in the English National Health Service. The interviews surfaced a series of narratives regarding hospital board oversight of patient safety. These elaborated on the role of trust and intelligence in highlighting the potential dangers and limitations of approaches to hospital board oversight which have been narrowly focused on a risk-based view of organisational performance. In response, a need to engage with the development of trust based organisational relationships is identified, in which effective board oversight is built on 'trust' characterised by styles of leadership and behaviours that are attentive to the needs and concerns of both staff and patients. Effective board oversight also requires the gathering and triangulating of 'intelligence' generated from both national and local information sources. We call for a re-imagination of hospital board oversight in the light of these different perspectives and articulate an emerging research agenda in this area.

Regulatory oversight of nuclear safety in Finland. Annual report 2011

Energy Technology Data Exchange (ETDEWEB)

Kainulainen, E. (ed.)

2012-07-01

The report constitutes the report on regulatory control in the field of nuclear energy which the Radiation and Nuclear Safety Authority (STUK) is required to submit once a year to the Ministry of Employment and the Economy pursuant to Section 121 of the Nuclear Energy Decree. The report is also delivered to the Ministry of Environment, the Finnish Environment Institute, and the regional environmental authorities of the localities in which a nuclear facility is located. The regulatory control of nuclear safety in 2011 included the design, construction and operation of nuclear facilities, as well as nuclear waste management and nuclear materials. The first parts of the report explain the basics of nuclear safety regulation included as part of STUK's responsibilities, as well as the objectives of the operations, and briefly introduce the objects of regulation. The chapter concerning the development and implementation of legislation and regulations describes changes in nuclear legislation, as well as the progress of STUK's YVL Guide revision work. The section concerning the regulation of nuclear facilities contains an overall safety assessment of the nuclear facilities currently in operation or under construction. The chapter concerning the regulation of the final disposal project for spent nuclear fuel de-scribes the preparations for the final disposal project and the related regulatory activities. The section concerning nuclear non-proliferation describes the nuclear non-proliferation control for Finnish nuclear facilities and final disposal of spent nuclear fuel, as well as measures required by the Additional Protocol of the Safeguards Agreement. The chapter describing the oversight of security arrangements in the use of nuclear energy discusses oversight of the security arrangements in nuclear power plants and other plants, institutions and functions included within the scope of STUK's regulatory oversight. The chapter also discusses the national and

Approaches to the mathematical description of NPP operational safety management and oversight

International Nuclear Information System (INIS)

Bilej, D.V.; Berzhanskij, S.V.

2014-01-01

The paper presents analysis of features related to NPP operational safety management and oversight. According to analysis results, approaches are proposed to perform mathematical description of specific processes and to develop a scale for management to the current safety level as regards NPP power generation. Proposed approaches are making experimental equations and process approach of ISO-9001 quality system

Governmental oversight of prescribing medications: history of the US Food and Drug Administration and prescriptive authority.

Science.gov (United States)

Plank, Linda S

2011-01-01

The evolution of drug regulation and awarding of prescriptive authority is a complex and sometimes convoluted process that can be confusing for health care providers. A review of the history of how drugs have been manufactured and dispensed helps explain why this process has been so laborious and complicated. Because the federal and state governments have the responsibility for protecting the public, most regulations have been passed with the intentions of ensuring consumer safety. The current system of laws and regulations is the result of many years of using the legal system to correct drug marketing that had adverse health consequences. Government oversight will continue as prescribing medications transitions to an electronic form and as health care professionals in addition to physicians seek to gain prescriptive authority. © 2011 by the American College of Nurse-Midwives.

Institutional Oversight of Occupational Health and Safety for Research Programs Involving Biohazards.

Science.gov (United States)

Dyson, Melissa C; Carpenter, Calvin B; Colby, Lesley A

2017-06-01

Research with hazardous biologic materials (biohazards) is essential to the progress of medicine and science. The field of microbiology has rapidly advanced over the years, partially due to the development of new scientific methods such as recombinant DNA technology, synthetic biology, viral vectors, and the use of genetically modified animals. This research poses a potential risk to personnel as well as the public and the environment. Institutions must have appropriate oversight and take appropriate steps to mitigate the risks of working with these biologic hazards. This article will review responsibilities for institutional oversight of occupational health and safety for research involving biologic hazards.

Maintaining Oversight of Licensee Safety Culture. CSNI/WGHOF Survey Results

International Nuclear Information System (INIS)

2008-01-01

In preparation for this workshop, a survey was sent to members of the WGHOF in Autumn 2006. Purpose of the Survey was to explore and share the methods and approaches used to maintain oversight of licensee safety culture. 13 countries responded to the survey. The responses were used in the development of discussion topics and themes for this workshop. This presentation (slides) summarizes the results of the survey

Lessons Learned from a Five-year Evaluation of the Belgian Safety Culture Oversight Process

International Nuclear Information System (INIS)

Bernard, B.

2016-01-01

The Belgian Regulatory Body has implemented a Safety Culture oversight process since 2010. In a nutshell, this process is based on field observations provided by inspectors or safety analysts during any contact with a licencee (inspections, meetings, phone calls, etc). These observations are recorded within an observation (excel) sheet—aiming at describing factual and contextual issues — and are linked to IAEA Safety Culture attributes. It should be stressed that the purpose of the process is not to give a comprehensive view of a licencee safety culture but to address findings that require attention or action on the part of a licencee. In other words, gathering safety culture observations aims at identifying cultural, organizational or behavioural issues in order to feed a regulatory response to potential problems. Safety Culture Observations (SCO) are then fully integrated in routine inspection activities and must be seen as an input of the overall oversight process. As a result, the assessment of the SCO is inserted within the yearly safety evaluation report performed by Bel V and transmitted to the licencee. However, observing safety culture is not a natural approach for engineers. Guidance, training and coaching must be provided in order to open up safety dimensions to be captured. In other words, a SCO process requires a continuous support in order to promote a holistic and systemic view of safety.

State safety oversight program : audit of the tri-state oversight committee and the Washington metropolitan area transit authority, final audit report, March 4, 2010.

Science.gov (United States)

2010-03-04

The Federal Transit Administration (FTA) conducted an on-site audit of the safety program implemented by the Washington Metropolitan Area Transit Authority (WMATA) and overseen by the Tri-State Oversight Committee (TOC) between December 14 and 17, 20...

Nuclear Oversight Function at Krsko NPP

International Nuclear Information System (INIS)

Bozin, B.; Kavsek, D.

2010-01-01

The nuclear oversight function is used at the Krsko NPP constructively to strengthen safety and improve performance. Nuclear safety is kept under constant examination through a variety of monitoring techniques and activities, some of which provide an independent review. The nuclear oversight function at the Krsko NPP is accomplished by Quality and Nuclear Oversight Division (SKV). SKV has completed its mission through a combination of compliance, performance and effectiveness-based assessments. The performance-based assessment is an assessment using various techniques (observations, interviews, walk-downs, document reviews) to assure compliance with standards and regulations, obtain insight into performance, performance trends and also to identify opportunities to improve effectiveness of implementation. Generally, the performance-based approach to oversight function is based on some essential elements. The most important one which is developed and implemented is an oversight program (procedure). The program focuses on techniques, activities and objectives commensurate with their significance to plant operational safety. These techniques and activities are: self-assessments, assessments, audits, performance indicators, monitoring of corrective action program (CAP), industry independent reviews (such as IAEA's OSART and WANO Peer Review), industry benchmarking etc. Graded approach is an inherent product of a performance based program and ranking process. It is important not only to focus on the highest ranked performance based attributes but to lead to effective utilization of an oversight program. The attributes selected for oversight need to be based on plant specific experience, current industry operating experience, supplier's performance and quality issues. Collaboration within the industry and effective utility oversight of processes and design activities are essential for achieving good plant performance. So the oversight program must integrate relevant

Information exchange - DOE oversight programs

International Nuclear Information System (INIS)

Tubbs, D.C.; Field, H.C.

1988-01-01

Oversight programs are conducted by the U.S. Department of Energy to review activities carried out by field and contractor organizations. Two of these oversight programs focus on safeguards and security and on safety and health activities. These two programs are independent, but share many common objectives and review techniques. The mutual potential benefit was recognized from an exchange of information on review techniques. The first step in this exchange was the participation by an Office of Security Evaluations (OSE) staff member with the Office of Nuclear Safety (ONS) during their planning, conduct and reporting of a Technical Safety Appraisal (TSA). This paper briefly describes the OSE and ONS programs. It also identifies and analyzes the similarities and differences of the two programs. The purpose of this paper is to provide perspectives on the approach taken, the techniques used and the differences between two oversight programs conducted by the Department of Energy

Drug Safety

Science.gov (United States)

... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

Regulatory Oversight of Radioactive Sources through the Integrated Management of Safety and Security

International Nuclear Information System (INIS)

Horvath, K.

2016-01-01

The Hungarian Atomic Energy Authority (HAEA) has full regulatory competence; its mission is to oversee the safety and security of all the peaceful applications of atomic energy. All the radioactive sources having activity above the exemption level is registered and licensed both from safety and security points of view. The Hungarian central register of radioactive sources contains about 7,000 radioactive sources and 450 license holders. In order to use its limited resources the HAEA has decided to introduce an integrated regulatory oversight programme. Accordingly, during the licensing process and inspection activities the HAEA intends to assess both safety and security aspects at the same time. The article describes the Hungarian the various applications of radioactive materials, and summarizes the preparation activities of the HAEA. (author)

Review of the OSHA framework for oversight of occupational environments.

Science.gov (United States)

Choi, Jae-Young; Ramachandran, Gurumurthy

2009-01-01

The OSHA system for oversight of chemicals in the workplace was evaluated to derive lessons for oversight of nanotechnology. Criteria relating to the development, attributes, evolution, and outcomes of the system were used for evaluation that was based upon quantitative expert elicitation and historical literature analysis. The oversight system had inadequate resources in terms of finances, expertise, and personnel, and insufficient incentive for compliance. The system showed a lack of flexibility in novel situations. There were minimal requirements on companies for data on health and safety of their products. These factors have a strong influence on public confidence and health and safety. The oversight system also scored low on attributes such as public input, transparency, empirical basis, conflict of interest, and informed consent. The experts in our sample tend to believe that the current oversight system for chemicals in the workplace is neither adequate nor effective. It is very likely that the performance of the OSHA oversight system for nanomaterials will be equally inadequate.

Designing oversight for nanomedicine research in human subjects: systematic analysis of exceptional oversight for emerging technologies

International Nuclear Information System (INIS)

Wolf, Susan M.; Jones, Cortney M.

2011-01-01

The basic procedures and rules for oversight of U.S. human subjects research have been in place since 1981. Certain types of human subjects research, however, have provoked creation of additional mechanisms and rules beyond the Department of Health and Human Services (DHHS) Common Rule and Food and Drug Administration (FDA) equivalent. Now another emerging domain of human subjects research—nanomedicine—is prompting calls for extra oversight. However, in 30 years of overseeing research on human beings, we have yet to specify what makes a domain of scientific research warrant extra oversight. This failure to systematically evaluate the need for extra measures, the type of extra measures appropriate for different challenges, and the usefulness of those measures hampers efforts to respond appropriately to emerging science such as nanomedicine. This article evaluates the history of extra oversight, extracting lessons for oversight of nanomedicine research in human beings. We argue that a confluence of factors supports the need for extra oversight, including heightened uncertainty regarding risks, fast-evolving science yielding complex and increasingly active materials, likelihood of research on vulnerable participants including cancer patients, and potential risks to others beyond the research participant. We suggest the essential elements of the extra oversight needed.

Designing oversight for nanomedicine research in human subjects: systematic analysis of exceptional oversight for emerging technologies

Science.gov (United States)

Wolf, Susan M.; Jones, Cortney M.

2011-04-01

The basic procedures and rules for oversight of U.S. human subjects research have been in place since 1981. Certain types of human subjects research, however, have provoked creation of additional mechanisms and rules beyond the Department of Health & Human Services (DHHS) Common Rule and Food and Drug Administration (FDA) equivalent. Now another emerging domain of human subjects research—nanomedicine—is prompting calls for extra oversight. However, in 30 years of overseeing research on human beings, we have yet to specify what makes a domain of scientific research warrant extra oversight. This failure to systematically evaluate the need for extra measures, the type of extra measures appropriate for different challenges, and the usefulness of those measures hampers efforts to respond appropriately to emerging science such as nanomedicine. This article evaluates the history of extra oversight, extracting lessons for oversight of nanomedicine research in human beings. We argue that a confluence of factors supports the need for extra oversight, including heightened uncertainty regarding risks, fast-evolving science yielding complex and increasingly active materials, likelihood of research on vulnerable participants including cancer patients, and potential risks to others beyond the research participant. We suggest the essential elements of the extra oversight needed.

Evaluating oversight systems for emerging technologies: a case study of genetically engineered organisms.

Science.gov (United States)

Kuzma, Jennifer; Najmaie, Pouya; Larson, Joel

2009-01-01

The U.S. oversight system for genetically engineered organisms (GEOs) was evaluated to develop hypotheses and derive lessons for oversight of other emerging technologies, such as nanotechnology. Evaluation was based upon quantitative expert elicitation, semi-standardized interviews, and historical literature analysis. Through an interdisciplinary policy analysis approach, blending legal, ethical, risk analysis, and policy sciences viewpoints, criteria were used to identify strengths and weaknesses of GEOs oversight and explore correlations among its attributes and outcomes. From the three sources of data, hypotheses and broader conclusions for oversight were developed. Our analysis suggests several lessons for oversight of emerging technologies: the importance of reducing complexity and uncertainty in oversight for minimizing financial burdens on small product developers; consolidating multi-agency jurisdictions to avoid gaps and redundancies in safety reviews; consumer benefits for advancing acceptance of GEO products; rigorous and independent pre- and post-market assessment for environmental safety; early public input and transparency for ensuring public confidence; and the positive role of public input in system development, informed consent, capacity, compliance, incentives, and data requirements and stringency in promoting health and environmental safety outcomes, as well as the equitable distribution of health impacts. Our integrated approach is instructive for more comprehensive analyses of oversight systems, developing hypotheses for how features of oversight systems affect outcomes, and formulating policy options for oversight of future technological products, especially nanotechnology products.

42 CFR 137.368 - Is the Secretary responsible for oversight and compliance of health and safety codes during...

Science.gov (United States)

2010-10-01

... compliance of health and safety codes during construction projects being performed by a Self-Governance Tribe... SERVICES TRIBAL SELF-GOVERNANCE Construction Roles of the Secretary in Establishing and Implementing Construction Project Agreements § 137.368 Is the Secretary responsible for oversight and compliance of health...

Oversight and management of a cell therapy clinical trial network: experience and lessons learned.

Science.gov (United States)

Moyé, Lemuel A; Sayre, Shelly L; Westbrook, Lynette; Jorgenson, Beth C; Handberg, Eileen; Anwaruddin, Saif; Wagner, Kristi A; Skarlatos, Sonia I

2011-09-01

The Cardiovascular Cell Therapy Research Network (CCTRN), sponsored by the National Heart, Lung, and Blood Institute (NHLBI), was established to develop, coordinate, and conduct multiple collaborative protocols testing the effects of cell therapy on cardiovascular diseases. The Network was born into a difficult political and ethical climate created by the recent removal of a dozen drugs from the US formulary and the temporary halting of 27 gene therapy trials due to safety concerns. This article describes the Network's challenges as it initiated three protocols in a polarized cultural atmosphere at a time when oversight bodies were positioning themselves for the tightest vigilance of promising new therapies. Effective strategies involving ongoing education, open communication, and relationship building with the oversight community are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Brief introduction of USA new reactor oversight process and suggestions for our country

International Nuclear Information System (INIS)

Hao Xiaofeng; Chen Rui; Zhou Limin; Wang Xiuqing

2002-01-01

The NRC New Reactor Oversight Process focuses the nuclear safety supervision on the 3 areas: Reactor Safety, Radiation safety and Plant Security. Within the 3 areas, 7 cornerstones are detailed for the purpose. They are Initiating Events, Mitigating Systems, Barrier Integrity, Emergency Preparedness, Occupational Radiation Protection, Public Radiation Safety and Physical Protection. On cooperating with the inspections, the new process ensures a more effective, objective and timely evaluation of the safety level of the operating nuclear power plants. On considering the practices and the status in China nuclear safety supervision, the authors have to learn something from the NRC New Reactor Oversight Process. The authors must make an optimization on Chinese limited resources and put the emphasis on the issues with high risk in order to prevent the occurrence of the accidents. Properly inducing some ideas and methodology from the NRC New Reactor Oversight Process will benefit the development and perfection of the supervision mode of the NNSA

Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 2: Appendices

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-31

On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 2 contains copies of the documents which established the relationship between NRC, DOE, USEC, and DOL (Dept of Labor) required to facilitate regulatory oversight transition.

Regulatory Oversight Program, July 1, 1993 - March 3, 1997. Volume 2: Appendices

International Nuclear Information System (INIS)

1997-01-01

On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 2 contains copies of the documents which established the relationship between NRC, DOE, USEC, and DOL (Dept of Labor) required to facilitate regulatory oversight transition

Aviation Safety: FAA Oversight of Repair Stations Needs Improvement

Science.gov (United States)

1997-10-24

This report by the General Accounting Office examines the Federal Aviation : Administration's (FAA) oversight of the aviation repair station industry. : Specifically, this report addresses the following questions: (1) What is the : nature and scope o...

Contemporary Approaches to Safety Culture: Lessons from Developing a Regulatory Oversight Approach

International Nuclear Information System (INIS)

Goebel, V.; Heppell-Masys, K.

2016-01-01

The Canadian Nuclear Safety Commission (CNSC) regulates the use of nuclear energy and materials to protect health, safety, security and the environment, and to implement Canada’s international commitments on the peaceful use of nuclear energy; and to disseminate objective scientific, technical and regulatory information to the public. In the late 1990s, the CNSC conducted research into an Organization and Management (O&M) assessment method. Based on this research the CNSC conducted O&M assessments at all Canadian nuclear power plants and conducted additional assessments of nuclear research and uranium mine and mill operations. The results of these assessments were presented to licencees and used to inform their ongoing actions related to safety culture. Additional safety culture outreach and oversight activities provided licencees with opportunities to develop effective safety culture assessment methods, to share best practices across industry, and to strive for continual improvement of their organizations. Recent changes to the Canadian Standards Association (CSA) management system standard have resulted in the inclusion of requirements associated to safety culture and human performance. Representatives from several sectors of Canada’s nuclear industry, as well as participation from regulators such as the CNSC took part to the development of this consensus standard. Specifically, these requirements focus on monitoring and understanding safety culture, integrating safety into all of the requirements of the management system, committing workers to adhere to the management system and supporting excellence in workers’ performance. The CNSC is currently developing a regulatory document on safety culture which includes key concepts applicable to all licencees and specific requirements related to self-assessment, and additional guidance for nuclear power plants. Developing a regulatory document on safety culture requires consultation and fact finding initiatives at

Dynamic oversight: implementation gaps and challenges

Science.gov (United States)

Howard, John

2011-04-01

Nanotechnology is touted as a transformative technology in that it is predicted to improve many aspects of human life. There are hundreds of products in the market that utilize nanostructures in their design, such as composite materials made out of carbon or metal oxides. Potential risks to consumers, to the environment, and to workers from the most common passive nanomaterial—carbon nanotubes—are emerging through scientific research. Newer more active nanostructures—such as cancer therapies and targeted drug systems—are also increasing in use and are raising similar risk concerns. Governing the risks to workers is the subject of this commentary. The Occupational Safety and Health Act of 1970 grants the Occupational Safety and Health Administration the legal authority to set occupational health standards to insure that no worker suffers material impairment of health from work. However, setting a standard to protect workers from nanotechnology risks may occur some time in the future because the risks to workers have not been well characterized scientifically. Alternative risk governances—such as dynamic oversight through stakeholder partnerships, "soft law" approaches, and national adoption of international consensus standards—are evaluated in this article.

Dynamic oversight: implementation gaps and challenges

International Nuclear Information System (INIS)

Howard, John

2011-01-01

Nanotechnology is touted as a transformative technology in that it is predicted to improve many aspects of human life. There are hundreds of products in the market that utilize nanostructures in their design, such as composite materials made out of carbon or metal oxides. Potential risks to consumers, to the environment, and to workers from the most common passive nanomaterial—carbon nanotubes—are emerging through scientific research. Newer more active nanostructures—such as cancer therapies and targeted drug systems—are also increasing in use and are raising similar risk concerns. Governing the risks to workers is the subject of this commentary. The Occupational Safety and Health Act of 1970 grants the Occupational Safety and Health Administration the legal authority to set occupational health standards to insure that no worker suffers material impairment of health from work. However, setting a standard to protect workers from nanotechnology risks may occur some time in the future because the risks to workers have not been well characterized scientifically. Alternative risk governances—such as dynamic oversight through stakeholder partnerships, “soft law” approaches, and national adoption of international consensus standards—are evaluated in this article.

Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 3

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-31

On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations (ORO) to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 3 contains copies of two reports that document the DOE/ORO regulatory oversight inspection and enforcement history for each gaseous diffusion plant site. Each report provides a formal mechanism by which DOE/ORO could communicate the inspection and enforcement history to NRC. The reports encompass the inspection activities that occurred during July 1, 1993 through March 2, 1997.

Oversight and Influencing of Licensee Leadership and Management for Safety, Including Safety Culture - Regulatory Approaches and Methods. Proceedings of an NEA/IAEA Workshop, Chester, United Kingdom, 26-28 September 2011

International Nuclear Information System (INIS)

2012-01-01

Both regulators and the nuclear industry recognise the need for licensees to develop a strong, positive safety culture to support successful and sustainable nuclear safety performance. A number of reports have been issued by the IAEA and the NEA on the role of the regulator in relation to oversight of safety culture (References 1 to 5). There has been less clarity on how this should be achieved - in particular, with regard to strategies and practical approaches for maintaining oversight of, and influencing, those facets of licensee leadership and management which have a profound influence on safety culture. In recognition of this, the CSNI Working Group on Human and Organisational Factors (WGHOF), together with the CNRA Working Group on Inspection Practices (WGIP) and the IAEA, organised a workshop in Chester, United Kingdom, in May 2007 to provide a forum for gathering and sharing international experience, including good practices and learning points. The results of the workshop are reported in Reference 6. Workshop participants agreed that, in view of the rapidly developing approaches in this area, it would be sensible to hold a further workshop ('Chester 2') in 3-5 years in order to discuss how regulatory approaches have moved on and to share lessons learned from their application. In 2010, the WGIP hosted a workshop which included regulatory approaches for the assessment of licensee safety culture as a discussion topic. The outputs of the workshop included a list of commendable practices for monitoring and evaluating licensee safety culture (Reference 7). The 'Chester 2' workshop took place in September 2011. This report sets out the findings of the workshop, organised by the UK Office for Nuclear Regulation (ONR) on behalf of the CSNI/WGHOF and the IAEA. The workshop was attended by over 40 representatives of nuclear regulatory bodies and licensees from 15 countries plus IAEA and NEA. The workshop featured keynote papers on learning from major events, and from

75 FR 39954 - Oversight of Laboratory Developed Tests; Public Meeting; Change of Meeting Location

Science.gov (United States)

2010-07-13

...] Oversight of Laboratory Developed Tests; Public Meeting; Change of Meeting Location AGENCY: Food and Drug... location for the upcoming public meeting entitled ``Oversight of Laboratory Developed Tests.'' A new... the public meeting, FDA is announcing in this notice a new location for the public meeting. II. New...

Improving regulatory oversight of maintenance programs

International Nuclear Information System (INIS)

Cook, S.

2008-01-01

Safe nuclear power plant operation requires that risks due to failure or unavailability of Structures, Systems and Components (SSCs) be minimized. Implementation of an effective maintenance program is a key means for achieving this goal. In its regulatory framework, the important relationship between maintenance and safety is acknowledged by the CNSC. A high level maintenance program requirement is included in the Class I Facilities Regulations. In addition, the operating licence contains a condition based on the principle that the design function and performance of SSCs needs to remain consistent with the plant's design and analysis documents. Nuclear power plant licensees have the primary responsibility for safe operation of their facilities and consequently for implementation of a successful maintenance program. The oversight role of the Canadian Nuclear Safety Commission (CNSC) is to ensure that the licensee carries out that responsibility. The challenge for the CNSC is how to do this consistently and efficiently. Three opportunities for improvement to regulatory maintenance oversight are being pursued. These are related to the regulatory framework, compliance verification inspection activities and monitoring of self-reporting. The regulatory framework has been improved by clarifying expectations through the issuance of S-210 'Maintenance Programs for Nuclear Power Plants'. Inspection activities have been improved by introducing new maintenance inspections into the baseline program. Monitoring is being improved by making better use of self-reported and industry produced maintenance related performance indicators. As with any type of program change, the challenge is to ensure the consistent and optimal application of regulatory activities and resources. This paper is a summary of the CNSC's approach to improving its maintenance oversight strategy. (author)

Independent oversight review of the Department of Energy Quality Assurance Program for suspect/counterfeit parts. Revision 1

International Nuclear Information System (INIS)

1996-05-01

To address the potential threat that suspect/counterfeit parts could pose to DOE workers and the public, the Office of the Deputy Assistant Secretary for Oversight initiated a number of activities beginning in mid-1995. Oversight placed increased emphasis on the field's quality assurance-suspect/counterfeit parts programs during safety management evaluations, in keeping with the Office of Environment, Safety and Health (EH) oversight responsibilities, which include oversight of the Department's quality assurance (QA) programs. In addition, Oversight reviewed relevant policy documents and occurrence reports to determine the nature and magnitude of the problem within the Department. The results of that review, contained in an Office of Oversight report, Independent Oversight Analysis of Suspect/Counterfeit Parts Within the Department of Energy (November 1995), indicate a lack of consistency and comprehensiveness in the Department's QA-suspect/counterfeit parts program. A detailed analysis of the causes and impacts of the problem was recommended. In response, this review was initiated to determine the effectiveness of the Department's QA program for suspect/counterfeit parts. This study goes beyond merely assessing and reporting the status of the program, however. It is the authors intention to highlight the complex issues associated with suspect/counterfeit parts in the Department today and to present approaches that DOE managers might consider to address these issues

Independent oversight review of the Department of Energy Quality Assurance Program for suspect/counterfeit parts. Revision 1

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-05-01

To address the potential threat that suspect/counterfeit parts could pose to DOE workers and the public, the Office of the Deputy Assistant Secretary for Oversight initiated a number of activities beginning in mid-1995. Oversight placed increased emphasis on the field`s quality assurance-suspect/counterfeit parts programs during safety management evaluations, in keeping with the Office of Environment, Safety and Health (EH) oversight responsibilities, which include oversight of the Department`s quality assurance (QA) programs. In addition, Oversight reviewed relevant policy documents and occurrence reports to determine the nature and magnitude of the problem within the Department. The results of that review, contained in an Office of Oversight report, Independent Oversight Analysis of Suspect/Counterfeit Parts Within the Department of Energy (November 1995), indicate a lack of consistency and comprehensiveness in the Department`s QA-suspect/counterfeit parts program. A detailed analysis of the causes and impacts of the problem was recommended. In response, this review was initiated to determine the effectiveness of the Department`s QA program for suspect/counterfeit parts. This study goes beyond merely assessing and reporting the status of the program, however. It is the authors intention to highlight the complex issues associated with suspect/counterfeit parts in the Department today and to present approaches that DOE managers might consider to address these issues.

Recommendations for oversight of nanobiotechnology: dynamic oversight for complex and convergent technology

International Nuclear Information System (INIS)

Ramachandran, Gurumurthy; Wolf, Susan M.; Paradise, Jordan; Kuzma, Jennifer; Hall, Ralph; Kokkoli, Efrosini; Fatehi, Leili

2011-01-01

Federal oversight of nanobiotechnology in the U.S. has been fragmented and incremental. The prevailing approach has been to use existing laws and other administrative mechanisms for oversight. However, this “stay-the-course” approach will be inadequate for such a complex and convergent technology and may indeed undermine its promise. The technology demands a new, more dynamic approach to oversight. The authors are proposing a new oversight framework with three essential features: (a) the oversight trajectory needs to be able to move dynamically between “soft” and “hard” approaches as information and nano-products evolve; (b) it needs to integrate inputs from all stakeholders, with strong public engagement in decision-making to assure adequate analysis and transparency; and (c) it should include an overarching coordinating entity to assure strong inter-agency coordination and communication that can meet the challenge posed by the convergent nature of nanobiotechnology. The proposed framework arises from a detailed case analysis of several key oversight regimes relevant to nanobiotechnology and is informed by inputs from experts in academia, industry, NGOs, and government.

Proceedings of the CSNI/IAEA workshop on maintaining oversight of licensee safety culture - methods and approaches. Held from 21 to 23 May 2007 in Chester, UK

International Nuclear Information System (INIS)

2008-01-01

Weaknesses in safety culture have contributed to a number of high profile events in the nuclear and other high hazard sectors. The nuclear industry also faces challenges such as deregulation, out-sourcing, phase-out, upgrading and new builds which, if not properly planned and implemented, have the potential to make a negative impact on safety culture. These factors have fostered an increasing awareness of the need for licensees to develop a strong safety culture to support successful and sustainable nuclear safety performance. Regulatory bodies are taking a growing interest in this issue, and several are actively working to develop and implement approaches to maintaining oversight of licensee safety culture. However, these approaches are not yet well-established, and it was considered prudent to share experiences and developing methodologies in order to disseminate good practices and avoid potential pitfalls. An NEA/CSNI/IAEA workshop was therefore held in Chester, UK, in May 2007 in order to explore and discuss the approaches that different regulatory bodies are taking to maintain oversight of licensee safety culture. It was organised by the UK Nuclear Installations Inspectorate on behalf of the CSNI's Working Group on Human and Organisational Factors. This report sets out the findings of the Chester workshop. The workshop was attended by 50 representatives of nuclear regulatory bodies in 20 countries plus IAEA, WANO, EU and NEA. It included both specialists in safety culture and site/resident inspectors, whose attendance was facilitated by the CNRA's Working Group on Inspection Practices. The workshop comprised structured discussion sessions, in which a set of issues were explored by small discussion groups and then discussed in plenary, complemented by short presentations on national regulatory positions. The workshop revealed a broad consensus that nuclear regulators should have processes in place to maintain oversight of licensee safety culture. The approaches

Drug safety and the impact of drug warnings

DEFF Research Database (Denmark)

Hostenkamp, G.; Fischer, K. E.; Borch-Johnsen, K.

2016-01-01

Objective To analyse the impact of drug safety warnings from the European Medicines Agency (EMA) on drug utilisation and their interaction with information released through national reimbursement bodies. Methods Insurance claims data on anti-diabetic drug prescriptions in primary care in Germany...

Environment, safety, and health. Status of DOE's reorganization of its safety oversight function

International Nuclear Information System (INIS)

Bannerman, Carl J.; Cannon, Doris E.; Jones, Gary L.; Ulrich, Timothy W.

1990-01-01

Several major events that preceded the Secretary's decision to restructure DOE's management of its nuclear facilities were identified. The proposed restructuring plan, in concept, is designed to set in place an oversight framework, which will provide confidence in DOE's ability to operate its nuclear facilities in a safe manner. Further, on the basis of the previous work in this area as well as other independent studies, several issues were identified that may affect the success of the proposed restructuring plan

Alcohol and prescription drug safety in older adults

Directory of Open Access Journals (Sweden)

Zanjani F

2013-02-01

Full Text Available Faika Zanjani,1,2 Aasha I Hoogland,1 Brian G Downer11Department of Gerontology, 2Building Interdisciplinary Research Careers in Women's Health University of Kentucky, Lexington, KY, USABackground: The objectives of this study were to investigate older adults' knowledge of prescription drug safety and interactions with alcohol, and to identify pharmacists' willingness to disseminate prescription drug safety information to older adults.Methods: The convenience sample consisted of 48 older adults aged 54–89 years who were recruited from a local pharmacy and who completed surveys addressing their alcohol consumption, understanding of alcohol and prescription drug interactions, and willingness to change habits regarding alcohol consumption and prescription drugs. To address pharmacist willingness, 90 pharmacists from local pharmacies volunteered and answered questions regarding their willingness to convey prescription drug safety information to older adults.Results: Older adults reported low knowledge of alcohol and prescription drug safety, with women tending to be slightly more knowledgeable. More importantly, those who drank in the previous few months were less willing to talk to family and friends about how alcohol can have harmful interactions with prescription drugs, or to be an advocate for safe alcohol and prescription drug use than those who had not had a drink recently. Pharmacists reported that they were willing to convey prescription drug safety information to older adults via a variety of formats, including displaying or distributing a flyer, and directly administering a brief intervention.Conclusion: In this study, older adults were found to have inadequate knowledge of prescription drug safety and interactions with alcohol, but pharmacists who regularly come in contact with older adults indicated that they were ready and willing to talk to older adults about prescription drug safety. Future research should focus on interventions

49 CFR 659.27 - Internal safety and security reviews.

Science.gov (United States)

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Internal safety and security reviews. 659.27... State Oversight Agency § 659.27 Internal safety and security reviews. (a) The oversight agency shall... safety and security reviews in its system safety program plan. (b) The internal safety and security...

Investigation and consideration on the framework of oversight-based safety regulation. U.S. NRC 'Risk-Informed, Performance-Based' Regulation

International Nuclear Information System (INIS)

Saji, Gen

2001-01-01

Regulation on safety, environment and health in Japan has before today been intended to correspond with an accident at forms of reinforcement of national standards and monitoring, if any. However, as it was thought that such regulation reinforcement was afraid to bring some social rigidity, and to weaken independent responsibility, as a result, because of anxiety of losing peoples' merits inversely, some fundamental directivity such as respect of self-responsibility principle' and 'necessary and least limit of regulation' were selected as a part of political innovation. On the other hand, at a background of wide improvements on various indexing values showing operation results of nuclear power stations in U.S.A., private independent effort on upgrading of safety is told to largely affect at beginning of INPO (Institute of Nuclear Power Operations), without regulation reinforcement of NRC side. This is a proof of concrete effect of transfer to oversight-based safety regulation. Here were introduced on nuclear safety in U.S.A. at a base of some references obtained on entering the 'MIT summer specialist program. Nuclear system safety', on focussing at new safety regulation of NRC and its effect and so on, and adding some considerations based on some knowledge thereafter. (G.K.)

Nuclear health and safety

International Nuclear Information System (INIS)

1991-08-01

This paper is a review of environmental and safety programs at facilities in the Naval Reactors Program which shows no basis for allegations that unsafe conditions exist there or that the environment is being harmed by activities conducted there. The prototype reactor design provides safety measures that are consistent with commercial nuclear power plants. Minor incidents affecting safety and the environment have occurred, however, and dents affecting safety and the environment have occurred, however, and as with other nuclear facilities, past activities have caused environmental problems that require ongoing monitoring and vigilance. While the program has historically been exempt from most oversight, some federal and state environmental oversight agencies have recently been permitted access to Naval Reactors facilities for oversight purposes. The program voluntarily cooperates with the Nuclear Regulatory Commission regarding reactor modifications, safety improvements, and component reliability. In addition, the program and its contractors have established an extensive internal oversight program that is geared toward reporting the slightest deviations from requirements or procedures. Given the program's classification policies and requirements, it does not appear that the program routinely overclassifies information to prevent its release to the public or to avoid embarrassment. However, GAO did not some instances in which documents were improperly classified

Drug Safety Crises Management in Pharmacovigilance

Directory of Open Access Journals (Sweden)

Gloria Shalviri

2018-05-01

Full Text Available Background: Adverse drug events can cause serious consequences including death. A published report by Lazarou et al in 1998 showed that adverse drug events were the 4th to 6th leading cause of death in the United States. These events may lead to drug safety crises in some issues, which need to take crises management process for solving the problem and/or preventing similar events.Objectives: To evaluate nature of drug safety crises based on adverse events reported to Iranian Pharmacovigilance Center from 1999 through 2012. To mention success and failure outcomes of crises management process taken against detected crises.Methods: All adverse drug events received by Iranian Pharmacovigilance Center from 1999 through 2012 were evaluated for reports with fatal outcome. All alerting letters and manuscripts published by the Center during the same period were reviewed for detailed information on detected crises. World Health Organization definition was used for detecting drug safety crises.Results: Among 42036 registered cases in our database, 463 deaths were recorded. The most frequent suspected drug for adverse events with fatal outcome was ceftriaxone (100 cases. Ten different drug safety crises issues were detected during the study period and their successful or failure outcomes were evaluated. There were 112 issued alerting letters and 17 published manuscript during the same period which was monitored for detailed information.  Conclusion: It is necessary for national pharmacovigilance centers to have prepared programs for crises management. This could be useful for reducing drug related mortality.

Adverse drug reaction and concepts of drug safety in Ayurveda: An overview

Science.gov (United States)

Ajanal, Manjunath; Nayak, Shradda; Prasad, Buduru Sreenivasa; Kadam, Avinash

2013-01-01

Drug safety is a very basic and fundamental concept in medical practice. ADRs play an important role in assessing patient safety in any system of medicine. Pharmacovigilance study is thus significant to understand treatment outcomes. Current raised issue with respect to complementary and alternative system medicine (CAM) like Ayurveda is increased in number of safety reports along with report misinterpretation; this generates the negative impact on system. Although, Ayurveda which is holistic system of medicine from India has elaborated the causes and methods of drug-induced consequences along with preventive measures the available data in classical texts is scattered. The compilation and analysis along with modern concept drug safety is need of the hour. Present literature review was conducted from various compendium of Ayurveda and electronic data base with search terms of ‘Vyapad’, ‘Viruddha’, ‘Ahita’, ‘herb–herb interaction’, ‘idiosyncrasy’, ‘Prakritiviruddha’ etc. The reported information was analysed for the possible correlation on concept of ADR and Pharmacovigilance of current science. Overall review demonstrated that drug interaction, iatrogenic, over dose, administration of unsuitable drugs, reprehensive drug administration with respect to disease, complication from five procedural therapies (Panchakarma) and reprehensible preparation of mineral drug are nearer to the modern causes of ADR. Thus, concept of drug safety and ADR is not new to the Ayurveda. The concept “Drug which is not appropriate to be used as medicine”(Abheshaja) of Ayurveda sounds similar as that of modern pharmacovigilance. PMID:24563588

Regulatory Expectations for Safety Culture

Energy Technology Data Exchange (ETDEWEB)

Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2014-05-15

The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety.

Regulatory Expectations for Safety Culture

International Nuclear Information System (INIS)

Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung

2014-01-01

The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety

Patient Drug Safety Reporting: Diabetes Patients' Perceptions of Drug Safety and How to Improve Reporting of Adverse Events and Product Complaints.

Science.gov (United States)

Patel, Puja; Spears, David; Eriksen, Betina Østergaard; Lollike, Karsten; Sacco, Michael

2018-03-01

Global health care manufacturer Novo Nordisk commissioned research regarding awareness of drug safety department activities and potential to increase patient feedback. Objectives were to examine patients' knowledge of pharmaceutical manufacturers' responsibilities and efforts regarding drug safety, their perceptions and experiences related to these efforts, and how these factors influence their thoughts and behaviors. Data were collected before and after respondents read a description of a drug safety department and its practices. We conducted quantitative survey research across 608 health care consumers receiving treatment for diabetes in the United States, Germany, United Kingdom, and Italy. This research validated initial, exploratory qualitative research (across 40 comparable consumers from the same countries) which served to guide design of the larger study. Before reading a drug safety department description, 55% of respondents were unaware these departments collect safety information on products and patients. After reading the description, 34% reported the department does more than they expected to ensure drug safety, and 56% reported "more confidence" in the industry as a whole. Further, 66% reported themselves more likely to report an adverse event or product complaint, and 60% reported that they were more likely to contact a drug safety department with questions. The most preferred communication methods were websites/online forums (39%), email (27%), and telephone (25%). Learning about drug safety departments elevates consumers' confidence in manufacturers' safety efforts and establishes potential for patients to engage in increased self-monitoring and reporting. Study results reveal potentially actionable insights for the industry across patient and physician programs and communications.

Impact of biomarker development on drug safety assessment

International Nuclear Information System (INIS)

Marrer, Estelle; Dieterle, Frank

2010-01-01

Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

Tennessee Oversight Agreement annual report, May 31, 1994--June 30, 1995

International Nuclear Information System (INIS)

1995-01-01

The Tennessee Department of Environment and Conservation's DOE Oversight Division (TDEC/DOE-O) is responsible for assuring the citizens of Tennessee that their health, safety and environment on the Oak Ridge Reservation are protected and that appropriate remedial action is taken to provide this protection. TDEC/DOE-O has five program sections that reflect the organizational structure of the TDEC Bureau of Environment Divisions, as well as DOE's Environmental Safety and Health, Waste Management, and Environmental Restoration Programs

12 CFR 985.4 - Finance Board oversight.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Finance Board oversight. 985.4 Section 985.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD OFFICE OF FINANCE THE OFFICE OF FINANCE § 985.4 Finance Board oversight. (a) Oversight and enforcement actions. The Finance Board shall have the same regulatory oversight authority and enforcement powers...

A Study on Drug Safety Monitoring Program in India

Science.gov (United States)

Ahmad, A.; Patel, Isha; Sanyal, Sudeepa; Balkrishnan, R.; Mohanta, G. P.

2014-01-01

Pharmacovigilance is useful in assuring the safety of medicines and protecting the consumers from their harmful effects. A number of single drugs as well as fixed dose combinations have been banned from manufacturing, marketing and distribution in India. An important issue about the availability of banned drugs over the counter in India is that sufficient adverse drug reactions data about these drugs have not been reported. The most common categories of drugs withdrawn in the last decade were nonsteroidal antiinflammatory drugs (28%), antidiabetics (14.28%), antiobesity (14.28%), antihistamines (14.28%), gastroprokinetic drugs (7.14%), breast cancer and infertility drugs (7.14%), irritable bowel syndrome and constipation drugs (7.14%) and antibiotics (7.14%). Drug withdrawals from market were made mainly due to safety issues involving cardiovascular events (57.14%) and liver damage (14.28%). Majority of drugs have been banned since 3-5 years in other countries but are still available for sale in India. The present study compares the drug safety monitoring systems in the developed countries such as the USA and UK and provides implications for developing a system that can ensure the safety and efficacy of drugs in India. Absence of a gold standard for a drug safety surveillance system, variations in culture and clinical practice across countries makes it difficult for India to completely adopt another country's practices. There should be a multidisciplinary approach towards drug safety that should be implemented throughout the entire duration spanning from drug discovery to usage by consumers. PMID:25425751

Regulatory oversight strategy for chemistry program at Canadian nuclear power plants

International Nuclear Information System (INIS)

Kameswaran; Ram

2012-09-01

Chemistry program is one of the essential programs for the safe operation of a nuclear power plant. It helps to ensure the necessary integrity, reliability and availability of plant structures, systems and components important to safety. Additionally, the program plays an important role in asset preservation, limiting radiation exposure and environmental protection. A good chemistry program will minimize corrosion of materials, reduce activation products, minimize of the buildup of radioactive material leading to occupational radiation exposure and it helps limit the release of chemicals and radioactive materials to the environment. The legal basis for the chemistry oversight at Canadian NPPs is established by the Nuclear Safety and Control Act and its associated regulations. It draws on the Canadian Nuclear Safety Commission's regulatory framework and NPP operating license conditions that include applicable standards such as CAN/CSA N286-05 Management System Requirements for Nuclear Power Plants. This paper focuses on the regulatory oversight strategy used in Canada to assess the performance of chemistry program at the nuclear power plants (NPPs) licensed by CNSC. The strategy consists of a combination of inspection and performance monitoring activities. The activities are further supported from information gathered through staff inspections of cross-cutting areas such as maintenance, corrective-action follow-ups, event reviews and safety related performance indicators. (authors)

Regulatory Oversight Program, July 1, 1993 - March 3, 1997. Volume 1

International Nuclear Information System (INIS)

1997-09-01

On July 1, 1993, a Regulatory Oversight (RO) organization was established within the United States Department of Energy (DOE), Oak Ridge Operations (ORO) to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the RO program was to ensure continued plant safety, safeguards and security while the Paducah and Portsmouth gaseous diffusion plants (GDPs) transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). These activities were performed under the authority of the lease agreement between DOE and USEC until NRC issued a Certificate of Compliance or approved a Compliance Plan pursuant to Section 1701 of the Atomic Energy Act of 1954, as amended, and assumed regulatory responsibility. This report chronicles the formal development, operation and key activities of the RO organization from its beginning in July 1993, until the turnover of the regulatory oversight responsibility to the NRC on March 3, 1997. Through its evolution to closure, the RO program was a formal, proceduralized effort designed to provide consistent regulation and to facilitate transition to NRC. The RO Program was also a first-of-a-kind program for DOE. The process, experience, and lessons learned summarized herein should be useful as a model for transition of other DOE facilities to privatization or external regulation

Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 1

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-09-01

On July 1, 1993, a Regulatory Oversight (RO) organization was established within the United States Department of Energy (DOE), Oak Ridge Operations (ORO) to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the RO program was to ensure continued plant safety, safeguards and security while the Paducah and Portsmouth gaseous diffusion plants (GDPs) transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). These activities were performed under the authority of the lease agreement between DOE and USEC until NRC issued a Certificate of Compliance or approved a Compliance Plan pursuant to Section 1701 of the Atomic Energy Act of 1954, as amended, and assumed regulatory responsibility. This report chronicles the formal development, operation and key activities of the RO organization from its beginning in July 1993, until the turnover of the regulatory oversight responsibility to the NRC on March 3, 1997. Through its evolution to closure, the RO program was a formal, proceduralized effort designed to provide consistent regulation and to facilitate transition to NRC. The RO Program was also a first-of-a-kind program for DOE. The process, experience, and lessons learned summarized herein should be useful as a model for transition of other DOE facilities to privatization or external regulation.

13 CFR 120.1005 - Bureau of PCLP Oversight.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Bureau of PCLP Oversight. 120.1005 Section 120.1005 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Risk-Based Lender Oversight Supervision § 120.1005 Bureau of PCLP Oversight. SBA's Bureau of PCLP Oversight within...

5 CFR 330.611 - Oversight.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Oversight. 330.611 Section 330.611 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS RECRUITMENT, SELECTION, AND... Employees § 330.611 Oversight. OPM provides advice and assistance to agencies in implementing their Career...

12 CFR 370.10 - Oversight.

Science.gov (United States)

2010-01-01

... LIQUIDITY GUARANTEE PROGRAM § 370.10 Oversight. (a) Participating entities are subject to the FDIC's oversight regarding compliance with the terms of the temporary liquidity guarantee program. (b) A..., for the duration of the temporary liquidity guarantee program, to be subject to the FDIC's authority...

Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

Science.gov (United States)

2010-09-29

The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

32 CFR 2700.51 - Information Security Oversight Committee.

Science.gov (United States)

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Information Security Oversight Committee. 2700... MICRONESIAN STATUS NEGOTIATIONS SECURITY INFORMATION REGULATIONS Implementation and Review § 2700.51 Information Security Oversight Committee. The OMSN Information Security Oversight Committee shall be chaired...

Institutional Oversight of Occupational Health and Safety for Research Programs Involving Biohazards

OpenAIRE

Dyson, Melissa C; Carpenter, Calvin B; Colby, Lesley A

2017-01-01

Research with hazardous biologic materials (biohazards) is essential to the progress of medicine and science. The field of microbiology has rapidly advanced over the years, partially due to the development of new scientific methods such as recombinant DNA technology, synthetic biology, viral vectors, and the use of genetically modified animals. This research poses a potential risk to personnel as well as the public and the environment. Institutions must have appropriate oversight and take app...

Global patient safety and antiretroviral drug-drug interactions in the resource-limited setting.

Science.gov (United States)

Seden, Kay; Khoo, Saye H; Back, David; Byakika-Kibwika, Pauline; Lamorde, Mohammed; Ryan, Mairin; Merry, Concepta

2013-01-01

Scale-up of HIV treatment services may have contributed to an increase in functional health facilities available in resource-limited settings and an increase in patient use of facilities and retention in care. As more patients are reached with medicines, monitoring patient safety is increasingly important. Limited data from resource-limited settings suggest that medication error and antiretroviral drug-drug interactions may pose a significant risk to patient safety. Commonly cited causes of medication error in the developed world include the speed and complexity of the medication use cycle combined with inadequate systems and processes. In resource-limited settings, specific factors may contribute, such as inadequate human resources and high disease burden. Management of drug-drug interactions may be complicated by limited access to alternative medicines or laboratory monitoring. Improving patient safety by addressing the issue of antiretroviral drug-drug interactions has the potential not just to improve healthcare for individuals, but also to strengthen health systems and improve vital communication among healthcare providers and with regulatory agencies.

A survey of front-line paramedics examining the professional relationship between paramedics and physician medical oversight.

Science.gov (United States)

Foerster, Christopher R; Tavares, Walter; Virkkunen, Ilkka; Kämäräinen, Antti

2018-03-01

Paramedicine is often dependent on physician medical directors and their associated programs for direction and oversight. A positive relationship between paramedics and their oversight physicians promotes safety and quality care while a strained or ineffective one may threaten these goals. The objective of this study was to explore and understand the professional relationship between paramedics and physician medical oversight as viewed by front-line paramedics. All active front-line paramedics from four municipal paramedic services involving three medical oversight groups in Ontario were invited to complete an online survey. Five hundred and four paramedics were invited to participate in the study, with 242 completing the survey (48% response rate); 66% male, 76% primary care paramedics with an average of 13 (SD=9) years of experience. Paramedics had neutral or positive perceptions regarding their autonomy, opportunities to interact with their medical director, and medical director understanding of the prehospital setting. Paramedics perceived medical directives as rigid and ambiguous. A significant amount of respondents reported a perception of having provided suboptimal patient care due to fear of legal or disciplinary consequences. Issues of a lack of support for critical thinking and a lack of trust between paramedics and medical oversight groups were often raised. Paramedic perceptions of physician medical oversight were mixed. Concerning areas identified were perceptions of ambiguous written directives and concerns related to the level of trust and support for critical thinking. These perceptions may have implications for the system of care and should be explored further.

Safety-Related Contractor Activities at Nuclear Power Plants. New Challenges for Regulatory Oversight

International Nuclear Information System (INIS)

Chockie, Alan

2005-09-01

The use of contractors has been an integral and important part of the design, construction, operation, and maintenance of nuclear power plants. To ensure the safe and efficient completion of contracted tasks, each nuclear plant licensee has developed and refined formal contract management processes to meet their specific needs and plant requirements. Although these contract management processes have proven to be effective tools for the procurement of support and components tailored to the needs of nuclear power plants, contractor-related incidents and accidents have revealed some serious weaknesses with the implementation of these processes. Identifying and addressing implementation problems are becoming more complicated due to organizational and personnel changes affecting the nuclear power industry. The ability of regulators and licensees to effectively monitor and manage the safety-related performance of contractors will likely be affected by forthcoming organization and personnel changes due to: the aging of the workforce; the decline of the nuclear industry; and the deregulation of nuclear power. The objective of this report is to provide a review of current and potential future challenges facing safety-related contractor activities at nuclear power plants. The purpose is to assist SKI in establishing a strategy for the proactive oversight of contractor safety-related activities at Swedish nuclear power plants and facilities. The nature and role of contractors at nuclear plants is briefly reviewed in the first section of the report. The second section describes the essential elements of the contract management process. Although organizations have had decades of experience with the a contract management process, there remain a number of common implantation weaknesses that have lead to serious contractor-related incidents and accidents. These implementation weaknesses are summarized in the third section. The fourth section of the report highlights the

Safety-Related Contractor Activities at Nuclear Power Plants. New Challenges for Regulatory Oversight

Energy Technology Data Exchange (ETDEWEB)

Chockie, Alan [Chockie Group International, Inc., Seattle, WA (United States)

2005-09-15

The use of contractors has been an integral and important part of the design, construction, operation, and maintenance of nuclear power plants. To ensure the safe and efficient completion of contracted tasks, each nuclear plant licensee has developed and refined formal contract management processes to meet their specific needs and plant requirements. Although these contract management processes have proven to be effective tools for the procurement of support and components tailored to the needs of nuclear power plants, contractor-related incidents and accidents have revealed some serious weaknesses with the implementation of these processes. Identifying and addressing implementation problems are becoming more complicated due to organizational and personnel changes affecting the nuclear power industry. The ability of regulators and licensees to effectively monitor and manage the safety-related performance of contractors will likely be affected by forthcoming organization and personnel changes due to: the aging of the workforce; the decline of the nuclear industry; and the deregulation of nuclear power. The objective of this report is to provide a review of current and potential future challenges facing safety-related contractor activities at nuclear power plants. The purpose is to assist SKI in establishing a strategy for the proactive oversight of contractor safety-related activities at Swedish nuclear power plants and facilities. The nature and role of contractors at nuclear plants is briefly reviewed in the first section of the report. The second section describes the essential elements of the contract management process. Although organizations have had decades of experience with the a contract management process, there remain a number of common implantation weaknesses that have lead to serious contractor-related incidents and accidents. These implementation weaknesses are summarized in the third section. The fourth section of the report highlights the

32 CFR 2103.51 - Information Security Oversight Committee.

Science.gov (United States)

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Information Security Oversight Committee. 2103... BE DECLASSIFIED Implementation and Review § 2103.51 Information Security Oversight Committee. The NCS Information Security Oversight Committee shall be chaired by the Staff Counsel of the National Security...

[Post-marketing drug safety-risk management plan(RMP)].

Science.gov (United States)

Ezaki, Asami; Hori, Akiko

2013-03-01

The Guidance for Risk Management Plan(RMP)was released by the Ministry of Health, Labour and Welfare in April 2012. The RMP consists of safety specifications, pharmacovigilance plans and risk minimization action plans. In this paper, we outline post-marketing drug safety operations in PMDA and the RMP, with examples of some anticancer drugs.

13 CFR 120.1000 - Risk-Based Lender Oversight.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Risk-Based Lender Oversight. 120.1000 Section 120.1000 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Risk-Based Lender Oversight Supervision § 120.1000 Risk-Based Lender Oversight. (a) Risk-Based Lender...

Oversight Institutions Within the United Nations

DEFF Research Database (Denmark)

Pontoppidan, Caroline Aggestam

2015-01-01

This article will give a description of the role of internal audit and governance functions within the United Nations system. The United Nations has, during the last 10 years, worked to establish effective oversight services. Oversight, governance and hereunder the internal audit function has been...

76 FR 59142 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2011-09-23

...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the...., [[Page 59143

78 FR 20327 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2013-04-04

... Management Advisory Committee; Amendment of Notice AGENCY: Food and Drug Administration, HHS. ACTION: Notice... of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management... Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee...

Diabetes Drugs and Cardiovascular Safety

Directory of Open Access Journals (Sweden)

Ji Cheol Bae

2016-06-01

Full Text Available Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

Regulatory Activities for Licensee's Safety Culture

International Nuclear Information System (INIS)

Choi, Young Sung; Choi, Kwang Sik

2008-01-01

Weaknesses in safety culture have contributed to a number of incidents/accidents in the nuclear and other high hazard sectors worldwide in the past. These events have fostered an increasing awareness of the need for licensees to develop a strong safety culture to support successful and sustainable nuclear safety performance. Regulatory bodies are taking a growing interest in this issue, and several are actively working to develop and implement approaches to maintaining regulatory oversight of licensee safety culture. However, these approaches are not yet well-established, and it was considered prudent to share experiences and developing methodologies in order to disseminate good practices and avoid potential pitfalls. This paper presents the findings, conclusions and recommendations of international meetings and other countries' activities on safety culture and gives some suggestions for regulators to consider when planning regulatory oversight for licensee's safety culture

Overseeing oversight: governance of quality and safety by hospital boards in the English NHS.

Science.gov (United States)

Mannion, Russell; Davies, Huw; Freeman, Tim; Millar, Ross; Jacobs, Rowena; Kasteridis, Panos

2015-01-01

To contribute towards an understanding of hospital board composition and to explore board oversight of patient safety and health care quality in the English NHS. We reviewed the theory related to hospital board governance and undertook two national surveys about board management in NHS acute and specialist hospital trusts in England. The first survey was issued to 150 trusts in 2011/2012 and was completed online via a dedicated web tool. A total 145 replies were received (97% response rate). The second online survey was undertaken in 2012/2013 and targeted individual board members, using a previously validated standard instrument on board members' attitudes and competencies (the Board Self-Assessment Questionnaire). A total of 334 responses were received from 165 executive and 169 non-executive board members, providing at least one response from 95 of the 144 NHS trusts then in existence (66% response rate). Over 90% of the English NHS trust boards had 10-15 members. We found no significant difference in board size between trusts of different types (e.g. Foundation Trusts versus non-Foundation Trusts and Teaching Hospital Trusts versus non-Teaching Hospital Trusts). Clinical representation on boards was limited: around 62% had three or fewer members with clinical backgrounds. For about two-thirds of the trusts (63%), board members with a clinical background comprised less than 30% of the members. Boards were using a wide range and mix of quantitative performance metrics and soft intelligence (e.g. walk-arounds, patient stories) to monitor their organisations with regard to patient safety. The Board Self-Assessment Questionnaire data showed generally high or very high levels of agreement with desirable statements of practice in each of its six dimensions. Aggregate levels of agreement within each dimension ranged from 73% (for the dimension addressing interpersonal issues) to 85% (on the political). English NHS boards largely hold a wide range of attitudes and

Regional aviation safety organisations : enhancing air transport safety through regional cooperation

NARCIS (Netherlands)

Ratajczyk, Mikołaj Andrzej

2014-01-01

Aviation safety is of global concern. Yet 43% of countries worldwide lack the expertise and administrative capacity to ensure effective safety oversight of the aviation activities for which they are responsible under international law. With air traffic predicted to double in the next 15 years and

The concept of oversight, its connection to memory keeping and its relevance for the medium term: The findings of the RK and M initiative

International Nuclear Information System (INIS)

Hotzel, Stephan

2015-01-01

The medium term was introduced as the period of indirect oversight after repository closure, with timescales in the order of a few hundred years. While the importance of intrinsic control or 'passive' safety features in the post-closure phase of a geological repository has been recognised and stressed before, the role of oversight, by providing the capability to reduce or avoid some exposures, has come to the fore only recently. Oversight for the time being generally refers to 'watchful care' and society 'keeping an eye' on the technical system and the actual implementation of plans and decisions. In some regulatory frameworks oversight is indirectly required, for instance when mandating the creation of a land exclusion zone. In other frameworks, oversight is directly required, as illustrated, for instance, by the long-term stewardship concept of the US Environmental Protection Agency. Although sheer memory of the presence of the facility cannot be enough to constitute oversight, oversight and RK and M preservation do go hand in hand. For example, monitoring after repository closure fosters RK and M preservation, and vice versa. The presenter focused on terminology, potential oversight measures, and on roles and responsibilities of different stakeholders

Drug safety: withdrawn medications are only part of the picture.

Science.gov (United States)

Rawson, Nigel S B

2016-02-13

In a research article published in BMC Medicine, Onakpoya and colleagues provide a historical review of withdrawals of medications for safety reasons. However, withdrawn medications are only one part of the picture about how regulatory agencies manage drug risks. Moreover, medications introduced before the increased pre-marketing regulations and post-marketing monitoring systems instituted after the thalidomide tragedy have little relevance when considering the present drug safety picture because the circumstances under which they were introduced were completely different. To more fully understand drug safety management and regulatory agency actions, withdrawals should be evaluated within the setting and timeframe in which the medications are approved, which requires information about approvals and safety warnings. Studies are needed that provide a more comprehensive current picture of the identification and evaluation of drug safety risks as well as how regulatory agencies deal with them. Please see related research article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0553-2.

Safety and efficacy of drugs in pregnancy.

Science.gov (United States)

Knoppert, David

2011-01-01

Although most drugs are used to treat chronic or pregnancy-induced conditions during pregnancy and lactation, very few are studied in pregnant or breastfeeding women. The information we have on drugs taken during pregnancy and lactation is usually obtained after market approval through published case reports or case series and from pregnancy exposure or retrospective birth defect registries. Furthermore, generic drugs approved for use in this vulnerable population may be approved based on results from a male trial population. This disregards the changes that can occur during pregnancy which can affect the pharmacokinetics of drugs. In an effort to improve the information provided to prescribers, in 2008 the United States Food and Drug Administration proposed a change in product labelling where information from pregnancy exposure registries would be required. As of 2009, European Medicines Agency requires additional statements on use during pregnancy within drug labelling information. In Canada, it is anticipated that the efficacy and safety of drugs in pregnancy will be included under the Drug Safety and Effectiveness Network initiative, and that this will offer a unified approach for such assessments. Pregmedic, a non-profit organization for the advancement of safe and effective use of drugs in pregnancy, has presented a number of proposals and draft guidelines to Health Canada on the inclusion of pregnant women in pharmacokinetic studies and the establishment of registries for women who take drugs during pregnancy. Pregmedic advocates for ensuring that drugs indicated for women are studied in women.

A primer of drug safety surveillance: an industry perspective. Part I: Information flow, new drug development, and federal regulations.

Science.gov (United States)

Allan, M C

1992-01-01

To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part I of this series provides a background for the discussion of drug safety by defining the basic terms and showing the flow of safety information through a pharmaceutical company. The customers for adverse drug event data are identified to provide a basis for providing quality service. The development of a drug product is briefly reviewed to show the evolution of safety data. Drug development and safety are defined by federal regulations. These regulations are developed by the FDA with information from pharmaceutical manufacturers. The intent of the regulations and the accompanying guidelines is described. An illustration from the news media is cited to show an alternative, positive approach to handling an adverse event report. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text and additional readings are presented in an appendix. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction ;of the components

76 FR 40735 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2011-07-11

...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... East, Adelphi, MD. The conference center telephone number is: 301 985-7300. Contact Person: Kalyani...

75 FR 10490 - Joint Meeting of the Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management...

Science.gov (United States)

2010-03-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management Advisory... Drug Safety and Risk Management Advisory Committee. General Function of the Committees: To provide...

77 FR 65000 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

Science.gov (United States)

2012-10-24

...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide... Use (ETASU) before CDER's Drug Safety and Risk Management Advisory Committee (DSaRM). The Agency plans...

78 FR 30929 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

Science.gov (United States)

2013-05-23

...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide... (REMS) with elements to assure safe use (ETASU) before its Drug Safety and Risk Management Advisory...

78 FR 2677 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2013-01-14

...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... before February 7, 2013. Time allotted for each presentation may be limited. If the number of registrants...

76 FR 59143 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2011-09-23

...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the..., Adelphi, MD. The conference center telephone number is 301-985-7300. Contact Person: Kalyani Bhatt, Center...

How can nanobiotechnology oversight advance science and industry: examples from environmental, health, and safety studies of nanoparticles (nano-EHS)

International Nuclear Information System (INIS)

Wang Jing; Asbach, Christof; Fissan, Heinz; Hülser, Tim; Kuhlbusch, Thomas A. J.; Thompson, Drew; Pui, David Y. H.

2011-01-01

Nanotechnology has great potential to transform science and industry in the fields of energy, material, environment, and medicine. At the same time, more concerns are being raised about the occupational health and safety of nanomaterials in the workplace and the implications of nanotechnology on the environment and living systems. Studies on environmental, health, and safety (EHS) issues of nanomaterials have a strong influence on public acceptance of nanotechnology and, eventually, affect its sustainability. Oversight and regulation by government agencies and non-governmental organizations (NGOs) play significant roles in ensuring responsible and environmentally friendly development of nanotechnology. The EHS studies of nanomaterials can provide data and information to help the development of regulations and guidelines. We present research results on three aspects of EHS studies: physico-chemical characterization and measurement of nanomaterials; emission, exposure, and toxicity of nanomaterials; and control and abatement of nanomaterial releases using filtration technology. Measurement of nanoparticle agglomerates using a newly developed instrument, the Universal NanoParticle Analyzer (UNPA), is discussed. Exposure measurement results for silicon nanoparticles in a pilot scale production plant are presented, as well as exposure measurement and toxicity study of carbon nanotubes (CNTs). Filtration studies of nanoparticle agglomerates are also presented as an example of emission control methods.

77 FR 75176 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

Science.gov (United States)

2012-12-19

...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug... being rescheduled due to the postponement of the October 29-30, 2012, Drug Safety and Risk Management... Committee: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide...

Drug safety data mining with a tree-based scan statistic.

Science.gov (United States)

Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser R; Chan, Arnold K; Davis, Robert L; Graham, David; Platt, Richard; Andrade, Susan E; Boudreau, Denise; Gunter, Margaret J; Herrinton, Lisa J; Pawloski, Pamala A; Raebel, Marsha A; Roblin, Douglas; Brown, Jeffrey S

2013-05-01

In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance. We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic. Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation. The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs. Copyright © 2013 John Wiley & Sons, Ltd.

78 FR 16271 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2013-03-14

...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably...

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Health physics self-assessment and the nuclear regulatory oversight process at a nuclear power plant

International Nuclear Information System (INIS)

Schofield, R.S.

2003-01-01

The U.S. Nuclear Regulatory Commission has developed improvements in their Nuclear Power Plant inspection, assessment and enforcement practices. The objective of these changes was to link regulatory action with power plant performance through a risk- informed process which is intended to enhance objectivity. One of the Strategic Performance Areas of focus by the U.S. NRC is radiation safety. Two cornerstones, Occupational Radiation Safety and Public Radiation Safety, make up this area. These cornerstones are being evaluated through U.S. NRC Performance Indicators (PI) and baseline site inspections. Key to the U.S. NRC's oversight program is the ability of the licensee to implement a self-assessment program which pro-actively identifies potential problems and develops improvements to enhance management's effectiveness. The Health Physics Self-Assessment Program at San Onofre Nuclear Generating Station (SONGS) identifies radiation protection-related weakness or negative trends. The intended end result is improved performance through rapid problem identification, timely evaluation, corrective action and follow-up effectiveness reviews. A review of the radiation protection oversight process and the SONGS Health Physics Self-Assessment Program will be presented. Lessons learned and management tools, which evaluate workforce and Health Physics (HP) staff performance to improve radiological practices, are discussed. (author)

Flaws found in Los Alamos safety procedures

Science.gov (United States)

Gwynne, Peter

2017-12-01

A US government panel on nuclear safety has discovered a series of safety issues at the Los Alamos National Laboratory, concluding that government oversight of the lab's emergency preparation has been ineffective.

Nuclear health and safety

International Nuclear Information System (INIS)

1991-04-01

Numerous environmental, safety, and health problems found at other Department of Energy (DOE) defense nuclear facilities precipitated a review of these conditions at DOE's contractor-operated Pantex Plant, where our nation's nuclear weapons are assembled. This book focuses the review on examining key safety and health problems at Pantex and determining the need for external safety oversight of the plant

78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

Science.gov (United States)

2013-06-19

... inspections, and drive safety and quality throughout the supply chain. Implementation of these authorities... authorities granted to FDA under Title VII and their importance in ensuring drug safety, effectiveness, and.... FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and...

12 CFR 4.66 - Oversight and monitoring.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Oversight and monitoring. 4.66 Section 4.66 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY ORGANIZATION AND FUNCTIONS...; Contracting for Goods and Services § 4.66 Oversight and monitoring. The Deputy Comptroller for Resource...

Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

Science.gov (United States)

Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

2018-01-01

Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

12 CFR 1700.1 - Office of Federal Housing Enterprise Oversight.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Office of Federal Housing Enterprise Oversight. 1700.1 Section 1700.1 Banks and Banking OFFICE OF FEDERAL HOUSING ENTERPRISE OVERSIGHT, DEPARTMENT OF... of Federal Housing Enterprise Oversight. (a) Scope and authority. The Office of Federal Housing...

Determining animal drug combinations based on efficacy and safety.

Science.gov (United States)

Kratzer, D D; Geng, S

1986-08-01

A procedure for deriving drug combinations for animal health is used to derive an optimal combination of 200 mg of novobiocin and 650,000 IU of penicillin for nonlactating cow mastitis treatment. The procedure starts with an estimated second order polynomial response surface equation. That surface is translated into a probability surface with contours called isoprobs. The isoprobs show drug amounts that have equal probability to produce maximal efficacy. Safety factors are incorporated into the probability surface via a noncentrality parameter that causes the isoprobs to expand as safety decreases, resulting in lower amounts of drug being used.

Oversight Hearing on Drug Abuse Education Programs. Hearing before the Subcommittee on Elementary, Secondary, and Vocational Education of the Committee on Education and Labor. House of Representatives, 101st Congress, 2nd Session (Vancouver, Washington, September 6, 1990).

Science.gov (United States)

Congress of the U.S., Washington, DC. House Committee on Education and Labor.

The text of an oversight hearing on Drug Abuse Resistance Education (DARE) programs is presented in this document. Introductory statements by Representatives Jolene Unsoeld and Dale E. Kildee are presented. Testimony by these witnesses is included: (1) Roy Bondurant, student, and Roy "Skip" Bondurant, parent, Tenino, Washington; (2) Paul…

75 FR 23782 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

Science.gov (United States)

2010-05-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide...

Regulatory oversight on nuclear safety in Taiwan

Energy Technology Data Exchange (ETDEWEB)

Huang, T-T. [Atomic Energy Council, New Taipei City, Taiwan (China)

2014-07-01

Taiwan is a densely populated island and over 98% of its energy is imported, 16.5% of which is nuclear, in the form of materials and services. Ensuring that the most stringent nuclear safety standards are met therefore remains a priority for the government and the operator, Taiwan power Company (Taipower). There are eight nuclear power reactors in Taiwan, six of which are in operation and two are under construction. The first began operating nearly 40 years ago. For the time being the issue of whether to decommission or extend life of the operating units is also being discussed and has no conclusion yet. Nuclear energy has been a hot issue in debate over the past decades in Taiwan. Construction of Lungmen nuclear power plant, site selection of a final low-level waste disposal facility, installation of spent fuel dry storage facilities and safety of the currently operating nuclear power reactors are the issues that all Taiwanese are concerned most. In order to ensure the safety of nuclear power plant, the Atomic Energy Council (AEC) has implemented rigorous regulatory work over the past decades. After the Fukushima accident, AEC has conducted a reassessment program to re-evaluate all nuclear power plants in Taiwan, and asked Taipower to follow the technical guidelines, which ENSREG has utilized to implement stress test over nuclear power plants in Europe. In addition, AEC has invited two expert teams from OECD/NEA and ENSREG to conduct peer reviews of Taiwan's stress test national report in 2013. My presentation will focus on activities regulating safety of nuclear power programs. These will cover (A) policy of nuclear power regulation in Taiwan, (B)challenges of the Lungmen Plant, (C) post-Fukushima safety re-assessment, and (D)radioactive waste management. (author)

27 | Page OVERSIGHT FUNCTIONS OF THE LEGISLATURE: AN ...

African Journals Online (AJOL)

Fr. Ikenga

2004-09-06

Sep 6, 2004 ... its oversight functions remains weak because legislative role and ... ministers of his government and other officers in the public service of the Federation9, while .... 22 “Parliamentary Oversight of Finance and the Budgetary Process” - The ... Association of First Nations National, Chief Matthew Coon29 ...

Drug research methodology. Volume 2, The identification of drugs of interest in highway safety

Science.gov (United States)

1980-03-01

This report presents findings of a workshop on the identification of drugs that should be the focus of near-term highway safety research. Drugs of interest are those that have a potential to increase the likelihood of traffic crashes and their attend...

77 FR 2606 - Pipeline Safety: Random Drug Testing Rate

Science.gov (United States)

2012-01-18

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket ID PHMSA-2012-0004] Pipeline Safety: Random Drug Testing Rate AGENCY: Pipeline and Hazardous Materials... pipelines and operators of liquefied natural gas facilities must select and test a percentage of covered...

75 FR 9018 - Pipeline Safety: Random Drug Testing Rate

Science.gov (United States)

2010-02-26

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket ID PHMSA-2010-0034] Pipeline Safety: Random Drug Testing Rate AGENCY: Pipeline and Hazardous Materials... pipelines and operators of liquefied natural gas facilities must select and test a percentage of covered...

Regulatory control of nuclear safety in Finland. Annual report 2008

International Nuclear Information System (INIS)

Kainulainen, E.

2009-06-01

This report covers the regulatory control of nuclear safety in 2008, including the design, construction and operation of nuclear facilities, as well as nuclear waste management and nuclear materials. The control of nuclear facilities and nuclear waste management, as well as nuclear non-proliferation, concern two STUK departments: Nuclear Reactor Regulation and Nuclear Waste and Material Regulation. It constitutes the report on regulatory control in the field of nuclear energy, which the Radiation and Nuclear Safety Authority (STUK) is required to submit to the Ministry of Employment and the Economy pursuant to section 121 of the Finnish Nuclear Energy Decree. The first parts of the report explain the basics of the nuclear safety regulation included as part of STUK's responsibilities, as well as the objectives of the operations, and briefly introduce the objects of regulation. The chapter concerning the development and implementation of legislation and regulations describes changes in nuclear legislation, as well as the progress of STUK's YVL Guide revision. The chapter also includes a summary of the application of the updated YVL Guides to nuclear facilities. The section concerning the regulation of nuclear facilities contains a complete safety assessment of the nuclear facilities currently in operation or under construction. For the nuclear facilities in operation, the section describes plant operation, events during operation, annual maintenance, development of the plants and their safety, and observations made during monitoring. Data and observations gained during regulatory activities are reviewed with a focus on ensuring the safety functions of nuclear facilities and the integrity of structures and components. The report also includes a description of the oversight of the operations and quality management of organisations, oversight of operational experience feedback activities, and the results of these oversight activities. The radiation safety of nuclear

Blueprint for nuclear safety - a nonregulatory strategy

International Nuclear Information System (INIS)

Knight, J.P.

1989-01-01

The Department of Energy operates a nuclear complex that now numbers over 250 facilities nationwide, many of which date back to the 1940s and 1950s. In 1985, Secretary Herrington moved to establish the Office of Environment, Safety and Health, give it needed resources and authorities, and begin extensive environmental protection and safety evaluations of all major DOE sites and facilities. On the nuclear safety side this necessitates an integrated program that not only strengthens oversight but also builds DOE-wide technical capabilities and promotes safety performance. This has led up to focus our attention on three areas: (1) the DOE safety oversight system -- its resources, technical capabilities, and effectiveness; (2) the safety policy development and review; and (3) the Department's capabilities to foster technical inquisitiveness and overall excellence in safety performance. The essence of this approach is found in this last term -- performance. Performance that is results-oriented; founded on realized safety enhancements and risk reduction, not merely regulation for its own sake. Performance not merely in terms of hardware fixes, but also focusing on the human part of the safety equation

Health IT for Patient Safety and Improving the Safety of Health IT.

Science.gov (United States)

Magrabi, Farah; Ong, Mei-Sing; Coiera, Enrico

2016-01-01

Alongside their benefits health IT applications can pose new risks to patient safety. Problems with IT have been linked to many different types of clinical errors including prescribing and administration of medications; as well as wrong-patient, wrong-site errors, and delays in procedures. There is also growing concern about the risks of data breach and cyber-security. IT-related clinical errors have their origins in processes undertaken to design, build, implement and use software systems in a broader sociotechnical context. Safety can be improved with greater standardization of clinical software and by improving the quality of processes at different points in the technology life cycle, spanning design, build, implementation and use in clinical settings. Oversight processes can be set up at a regional or national level to ensure that clinical software systems meet specific standards. Certification and regulation are two mechanisms to improve oversight. In the absence of clear standards, guidelines are useful to promote safe design and implementation practices. Processes to identify and mitigate hazards can be formalised via a safety management system. Minimizing new patient safety risks is critical to realizing the benefits of IT.

Regulatory Oversight of the Legacy Gunner Uranium Mine and Mill Site in Northern Saskatchewan, Canada - 13434

Energy Technology Data Exchange (ETDEWEB)

Stenson, Ron; Howard, Don [Canadian Nuclear Safety Commission, P.O. Box 1046, Station B, 280 Slater Street, Ottawa ON K1P 5S9 (Canada)

2013-07-01

As Canada's nuclear regulator, the Canadian Nuclear Safety Commission (CNSC) is responsible for licensing all aspects of uranium mining, including remediation activities at legacy sites. Since these sites already existed when the current legislation came into force in 2000, and the previous legislation did not apply, they present a special case. The Nuclear Safety and Control Act (NSCA), was written with cradle-to- grave oversight in mind. Applying the NSCA at the end of a 'facilities' life-cycle poses some challenges to both the regulator and the proponent. When the proponent is the public sector, even more challenges can present themselves. Although the licensing process for legacy sites is no different than for any other CNSC license, assuring regulatory compliance can be more complicated. To demonstrate how the CNSC has approached the oversight of legacy sites the history of the Commission's involvement with the Gunnar uranium mine and mill site provides a good case study. The lessons learned from the CNSC's experience regulating the Gunnar site will benefit those in the future who will need to regulate legacy sites under existing or new legislation. (authors)

Systemic Approach to Safety from a Regulatory Perspective

International Nuclear Information System (INIS)

Edland, A.

2016-01-01

In Sweden and especially in the Swedish oversight of nuclear power plants there has been a strong commitment to the interactions between Man-Technology-Organization (MTO) for many years. Safety issues and the importance of working with these issues have often been highlighted in specific oversight actions. Since 30 years there has been a tradition and a development of experience in Sweden taking a systemic MTO approach to safety. Inspection teams have been created with both psychologists and technical expertise in order to cover the whole MTO perspective during oversight inspections at the nuclear power plants. Safety is based on preventive actions where both technology and human behaviour are taken into account. To do this, it is important to have knowledge about the different factors that influence the performance of individuals, groups and organizations. However, it is also important to remember to not only discuss humans, management and organizations in terms of their limitations, errors and shortcomings but also in terms of their strengths in stopping a chain of events, in learning, inventing and improving. Having an integrated view of safety, focussing on the relations between human, technology and organization (MTO) refers to a systemic perspective on how radiation safety are affected by the relationship between: Human’s abilities and limitations; Technical equipment and the surrounding environment; The organization and the opportunities this provides. The Section of Man-Technology-Organization in the Swedish authority consist today of 12 Human factors specialists with behaviour science education. The section is responsible for the oversight at nuclear power plants in many areas; safety management, leadership and organization, safety culture, competence assurance, fitness for duty, suitability, education and staffing, knowledge management, working conditions, MTO perspective/ergonomics of control room work and plant modification, incident analysis and risk

Exploring Machine Learning Techniques Using Patient Interactions in Online Health Forums to Classify Drug Safety

Science.gov (United States)

Chee, Brant Wah Kwong

2011-01-01

This dissertation explores the use of personal health messages collected from online message forums to predict drug safety using natural language processing and machine learning techniques. Drug safety is defined as any drug with an active safety alert from the US Food and Drug Administration (FDA). It is believed that this is the first…

Pooling, meta-analysis, and the evaluation of drug safety

Directory of Open Access Journals (Sweden)

Leizorovicz Alain

2002-03-01

Full Text Available Abstract Background The "integrated safety report" of the drug registration files submitted to health authorities usually summarizes the rates of adverse events observed for a new drug, placebo or active control drugs by pooling the safety data across the trials. Pooling consists of adding the numbers of events observed in a given treatment group across the trials and dividing the results by the total number of patients included in this group. Because it considers treatment groups rather than studies, pooling ignores validity of the comparisons and is subject to a particular kind of bias, termed "Simpson's paradox." In contrast, meta-analysis and other stratified analyses are less susceptible to bias. Methods We use a hypothetical, but not atypical, application to demonstrate that the results of a meta-analysis can differ greatly from those obtained by pooling the same data. In our hypothetical model, a new drug is compared to 1 a placebo in 4 relatively small trials in patients at high risk for a certain adverse event and 2 an active reference drug in 2 larger trials of patients at low risk for this event. Results Using meta-analysis, the relative risk of experiencing the adverse event with the new drug was 1.78 (95% confidence interval [1.02; 3.12] compared to placebo and 2.20 [0.76; 6.32] compared to active control. By pooling the data, the results were, respectively, 1.00 [0.59; 1.70] and 5.20 [2.07; 13.08]. Conclusions Because these findings could mislead health authorities and doctors, regulatory agencies should require meta-analyses or stratified analyses of safety data in drug registration files.

The Nuclear Regulator's Role in Assessing Licensee. Oversight of Vendor and Other Contracted Services

International Nuclear Information System (INIS)

2011-01-01

Contracted services are an integral part of the design, construction and operation of a nuclear facility. Changes in the nuclear industry sector, including varied availability of nuclear expertise, the expansion of the international supply market and the introduction of new technologies, have tended to increase licensees' use of contracted services. These changes have created challenges for licensees and regulators related to the retention of nuclear expertise, the effective management of the interfaces between the licensees and contractors, and the oversight of contractor manufacturing quality in the context of greater multinational diversity. The regulatory body must address these challenges to provide assurance that the licensees maintain their responsibility for the safety of the facilities, regardless of who provides goods and services or where the activities involved in the supply chain take place. This report is intended to assist regulatory bodies in assessing their current practices for the regulatory oversight of licensees' use of contractors, and adapting them where necessary to meet the evolving situation

The Regulatory Approach for the Assessment of Safety Culture in Germany: A Tool for Practical Use for Inspections

International Nuclear Information System (INIS)

Fassmann, W.; Beck, J.; Kopisch, C.

2016-01-01

Need for methods to assess licencees’ safety culture has been recognised since the Chernobyl accident. Several conferences organized by IAEA and OECD-NEA stated the need for regulatory oversight of safety culture and for suitable methods. In 2013, IAEA published a Technical Document (TECDOC 1707) on the process of safety culture oversight by regulatory authorities which leaves much room for regulators’ ways of performing safety culture oversight. In response to these developments, the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) as the federal regulatory body commissioned GRS in 2011 to develop a practical guidance for assessing licencees’ safety culture in the process of regulatory oversight. This research and development project was completed just recently. The publicly available documentation comprises a shorter guidance document with the indispensable information for an appropriate, practical application and a report with more detailed information about the scientific basis of this guidance. To achieve best possible adaptation to regulators’ needs, GRS asked members of the regulatory authority of Baden-Wuerttemberg (one of the federal states of Germany) for comments on a draft of the guidance which was then finalised by duly considering this highly valuable and favorable feedback. Decisions regarding future use rest with German regulatory authorities.

1992 Annual performance report for Environmental Monitoring and Oversight at Department of Energy facilities in New Mexico

Energy Technology Data Exchange (ETDEWEB)

1992-12-31

In October 1990 an Agreement-in-Principle (AIP) was entered into between the US Department of Energy (DOE) and the State of New Mexico for the purpose of supporting State oversight activities at DOE facilities in New Mexico. The State`s lead agency for the Agreement is the New Mexico Environment Department (NMED). DOE has agreed to provide the State with resources over a five year period to support State activities in environmental oversight, monitoring, access and emergency response to ensure compliance with applicable federal, state, and local laws at Los Alamos National Laboratory (LANL), Sandia National Laboratories (SNL), the Waste Isolation Pilot Plant (WIPP), and the Inhalation Toxicology Research Institute (ITRI). The Agreement is designed to assure the citizens of New Mexico that public health, safety and the environment are being protected through existing programs; DOE is in compliance with applicable laws and regulations; DOE has made substantial new commitments; cleanup and compliance activities have been prioritized; and a vigorous program of independent monitoring and oversight by the State is underway. This report relates the quality and effectiveness of the facilities` environmental monitoring and surveillance programs. This report satisfies that requirement for the January--December 1992 time frame.

1992 Annual performance report for Environmental Monitoring and Oversight at Department of Energy facilities in New Mexico

International Nuclear Information System (INIS)

1992-01-01

In October 1990 an Agreement-in-Principle (AIP) was entered into between the US Department of Energy (DOE) and the State of New Mexico for the purpose of supporting State oversight activities at DOE facilities in New Mexico. The State's lead agency for the Agreement is the New Mexico Environment Department (NMED). DOE has agreed to provide the State with resources over a five year period to support State activities in environmental oversight, monitoring, access and emergency response to ensure compliance with applicable federal, state, and local laws at Los Alamos National Laboratory (LANL), Sandia National Laboratories (SNL), the Waste Isolation Pilot Plant (WIPP), and the Inhalation Toxicology Research Institute (ITRI). The Agreement is designed to assure the citizens of New Mexico that public health, safety and the environment are being protected through existing programs; DOE is in compliance with applicable laws and regulations; DOE has made substantial new commitments; cleanup and compliance activities have been prioritized; and a vigorous program of independent monitoring and oversight by the State is underway. This report relates the quality and effectiveness of the facilities' environmental monitoring and surveillance programs. This report satisfies that requirement for the January--December 1992 time frame

Safety learning from drugs of the same class

DEFF Research Database (Denmark)

Stefansdottir, G; Knol, M J; Arnardottir, A H

2012-01-01

This study was aimed at assessing the extent of safety learning from data pertaining to other drugs of the same class. We studied drug classes for which the first and second drugs were centrally registered in the European Union from 1995 to 2008. We assessed whether adverse drug reactions (ADRs......) associated with one of the drugs also appeared in the Summary of Product Characteristics (SPC) of the other drug, either initially or during the postmarketing phase. We identified 977 ADRs from 19 drug pairs, of which 393 ADRs (40.2%) were listed in the SPCs of both drugs of a pair. Of these 393 that were...... present in both SPCs of a drug pair, 241 (61.3%) were present when the drug entered the market and 152 (30.7%) appeared in the postmarketing phase. The mention of ADRs in the SPCs of both same-class drugs in the postmarketing phase was associated with type A ADRs, marketing in the same regulator country...

41 CFR 105-53.133 - Information Security Oversight Office.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Information Security... FUNCTIONS Central Offices § 105-53.133 Information Security Oversight Office. (a) Creation and authority. The Information Security Oversight Office (ISOO), headed by the Director of ISOO, who is appointed by...

10 CFR 440.23 - Oversight, training, and technical assistance.

Science.gov (United States)

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Oversight, training, and technical assistance. 440.23... PERSONS § 440.23 Oversight, training, and technical assistance. (a) The Secretary and the appropriate..., directly or indirectly, training and technical assistance to any grantee or subgrantee. Such training and...

Tennessee Oversight Agreement combined annual reports, May 13, 1991--May 12, 1993

International Nuclear Information System (INIS)

1993-01-01

The Tennessee Oversight Agreement provides independent oversight and monitoring of the Department of Energy's activities on the Oak Ridge Reservation by the State. The agreement obligates the state to provide an annual report to DOE and for public distribution of the results of the DOE Oversight Division's monitoring and analysis activities and its findings of the quality and effectiveness of the Department of Energy's environmental monitoring and surveillance programs. The DOE Oversight Division's first report will discuss the status of the entire oversight agreement for the first two years of its existence. The 1991--1993 combined annual reports include a short history of the Division, a list of the Tennessee Oversight Agreement commitments and a status report on each of DOE Oversight Division's programs. Each Division program includes a descriptive status of its findings and recommendations. These findings and recommendations were also consolidated into a separate segment of the report (Chapter 7). Findings indicate there have been genuine successes in the areas of site access and data availability. More effort, however, is required in both of these areas before the state can verify that DOE and its contractors are meeting its obligations. Ambient surveillance monitoring by DOE is extensive. The DOE Oversight Division reviews this data to assure the state and its citizens that all areas of the environment are adequately protected by DOE operations. There is a noticeable lack of research and development in the technology for environmental remediation and radiological and mixed waste treatment, storage and disposal. The DOE Oversight Division's recommendations for improvement are provided with each of the findings listed in this report

Experience gained in enhancing operational safety at ComEd's nuclear power plants

International Nuclear Information System (INIS)

Elias, D.

1997-01-01

The following aspects of experience gained in enhancing operational safety at Comed's nuclear power plants are discussed: nuclear safety policy; centralization/decentralization; typical nuclear operating organization; safety review boards; human performance enhancement; elements of effective nuclear oversight

Nuclear safety in perspective

DEFF Research Database (Denmark)

Andersson, K.; Sjöberg, B.M.D.; Lauridsen, Kurt

2003-01-01

The aim of the NKS/SOS-1 project has been to enhance common understanding about requirements for nuclear safety by finding improved means of communicat-ing on the subject in society. The project, which has been built around a number of seminars, wassupported by limited research in three sub......-projects: Risk assessment Safety analysis Strategies for safety management The report describes an industry in change due to societal factors. The concepts of risk and safety, safety management and systems forregulatory oversight are de-scribed in the nuclear area and also, to widen the perspective, for other...

MORT User's Manual for use with the Management Oversight and Risk Tree analytical logic diagram. [Contains a list of System Safety Development Center publications

Energy Technology Data Exchange (ETDEWEB)

Knox, N.W.; Eicher, R.W.

1992-02-01

This report contains the User's Manual for MORT (Management Oversight and Risk Tree), a logic diagram in the form of a work sheet'' that illustrates a long series of interrelated questions. MORT is a comprehensive analytical procedure that provides a disciplined method for determining the causes and contributing factors of major accidents. Alternatively, it serves as a tool to evaluate the quality of an existing system. While similar in many respects to fault tree analysis, MORT is more generalized and presents over 1,500 specific elements of an ideal universal'' management program for optimizing environment, safety and health, and other programs. This User's Manual is intended to be used with the MORT diagram dated February 1992.

78 FR 14912 - International Aviation Safety Assessment (IASA) Program Change

Science.gov (United States)

2013-03-08

... Aviation Safety Assessment (IASA) Program Change AGENCY: Federal Aviation Administration (FAA), DOT. ACTION..., into the U.S., or codeshare with a U.S. air carrier, complies with international aviation safety... subject to that country's aviation safety oversight can serve the United States using its own aircraft or...

1993 Annual performance report for Environmental Oversight and Monitoring at Department of Energy facilities in New Mexico

International Nuclear Information System (INIS)

1993-01-01

In October of 1990, the New Mexico Environment Department entered into an agreement with the US Department of Energy (DOE) to create the Department of Energy Oversight and Monitoring Program. This program is designed to create an avenue for the State to ensure DOE facilities are in compliance with applicable environmental regulations, to allow the State oversight and monitoring independent of the DOE, to allow the State valuable input into remediation decision making, and to protect the environment and the public health and safety of New Mexicans concerning DOE facility activities. This agreement, called the Agreement in Principle (AIP), includes all four of New Mexico's DOE facilities: Los Alamos National Laboratory in Los Alamos; Sandia National Laboratories and the Inhalation Toxicology Research Institute on Kirtland Air Force Base in Albuquerque; and the Waste Isolation Pilot Plant near Carlsbad

Drug research methodology. Volume 5, Experimentation in drugs and highway safety : the study of drug effects on skills related to driving

Science.gov (United States)

1980-06-01

This report presents the findings of a workshop on experimental research in the area of drugs and highway safety. Complementing studies of drug use in different driving populations, experimentation here refers to studies performed under controlled co...

FDA drug safety communications: a narrative review and clinical considerations for older adults.

Science.gov (United States)

Marcum, Zachary A; Vande Griend, Joseph P; Linnebur, Sunny A

2012-08-01

The US Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. This has resulted in an increase in communication from the FDA in recent years about the safety profile of certain drugs. It is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public. To summarize 4 new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults. The FDA Web site was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature that supported the drug safety concern. FDA drug safety communications for 4 drugs were chosen because of the potential clinical importance in older adults. A warning for citalopram was made because of potential problems with QT prolongation in patients taking less than 40 mg per day. The evidence suggests minor changes in QT interval. Given the flat dose-response curve in treating depression with citalopram, the new 20-mg/d maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose-response relationship was found for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in older adults with decreased renal function. This medication should be used with caution in older

Nanotechnology, voluntary oversight, and corporate social performance: does company size matter?

International Nuclear Information System (INIS)

Kuzma, Jennifer; Kuzhabekova, Aliya

2011-01-01

In this article, we examine voluntary oversight programs for nanotechnology in the context of corporate social performance (CSP) in order to better understand the drivers, barriers, and forms of company participation in such programs. At the theoretical level, we use the management framework of CSP to understand the voluntary behavior of companies. At the empirical level, we investigate nanotech industry participation in the Environmental Protection Agency’s Nanoscale Materials Stewardship Program (NMSP) as an example of CSP, in order to examine the effects of company characteristics on CSP outcomes. The analysis demonstrates that, on the average, older and larger companies for which nanotech is one of the many business activities demonstrate greater CSP as judged by company actions, declarations, and self-evaluations. Such companies tended to submit more of the requested information to the NMSP, including specific information about health and safety, and to claim fewer of the submitted items as confidential business information. They were also more likely to have on-line statements of generic and nano-specific corporate social responsibility principles, policies, and achievements. The article suggests a need to encourage smaller and younger companies to participate in voluntary oversight programs for nanotechnology and presents options for better design of these programs.

Nanotechnology, voluntary oversight, and corporate social performance: does company size matter?

Science.gov (United States)

Kuzma, Jennifer; Kuzhabekova, Aliya

2011-04-01

In this article, we examine voluntary oversight programs for nanotechnology in the context of corporate social performance (CSP) in order to better understand the drivers, barriers, and forms of company participation in such programs. At the theoretical level, we use the management framework of CSP to understand the voluntary behavior of companies. At the empirical level, we investigate nanotech industry participation in the Environmental Protection Agency's Nanoscale Materials Stewardship Program (NMSP) as an example of CSP, in order to examine the effects of company characteristics on CSP outcomes. The analysis demonstrates that, on the average, older and larger companies for which nanotech is one of the many business activities demonstrate greater CSP as judged by company actions, declarations, and self-evaluations. Such companies tended to submit more of the requested information to the NMSP, including specific information about health and safety, and to claim fewer of the submitted items as confidential business information. They were also more likely to have on-line statements of generic and nano-specific corporate social responsibility principles, policies, and achievements. The article suggests a need to encourage smaller and younger companies to participate in voluntary oversight programs for nanotechnology and presents options for better design of these programs.

Food and Drug Administration Drug Approval Process: A History and Overview.

Science.gov (United States)

Williams, Christopher Ty

2016-03-01

In this article, the processing of investigational and new drug applications is described and the standard and expedited review processes are examined. The efforts of the US Food and Drug Administration to ensure greater agency transparency and fiscal responsibility and intensify oversight during the drug development and approval process are reviewed. Often attributed to a decrease in the number of uninsured adults, both the increase in prescription drug sales and the high costs associated with bringing a new drug to market highlight the necessity for a streamlined and cost-effective process to deliver these drugs safely and effectively. Copyright © 2016 Elsevier Inc. All rights reserved.

Pancreatic Safety of Incretin-Based Drugs - FDA and EMA Assessment

NARCIS (Netherlands)

Egan, Amy G.; Blind, Eberhard; Dunder, Kristina; de Graeff, Pieter A.; Hummer, B. Timothy; Bourcier, Todd; Rosebraugh, Curtis

2014-01-01

After evaluating a safety signal regarding pancreatitis and pancreatic cancer in patients using incretin-based drugs, the Food and Drug Administration and the European Medicines Agency conclude that assertions of a causal association are inconsistent with the data. With approximately 25.8 million

The practice of pre-marketing safety assessment in drug development.

Science.gov (United States)

Chuang-Stein, Christy; Xia, H Amy

2013-01-01

The last 15 years have seen a substantial increase in efforts devoted to safety assessment by statisticians in the pharmaceutical industry. While some of these efforts were driven by regulations and public demand for safer products, much of the motivation came from the realization that there is a strong need for a systematic approach to safety planning, evaluation, and reporting at the program level throughout the drug development life cycle. An efficient process can help us identify safety signals early and afford us the opportunity to develop effective risk minimization plan early in the development cycle. This awareness has led many pharmaceutical sponsors to set up internal systems and structures to effectively conduct safety assessment at all levels (patient, study, and program). In addition to process, tools have emerged that are designed to enhance data review and pattern recognition. In this paper, we describe advancements in the practice of safety assessment during the premarketing phase of drug development. In particular, we share examples of safety assessment practice at our respective companies, some of which are based on recommendations from industry-initiated working groups on best practice in recent years.

77 FR 10666 - Pipeline Safety: Post Accident Drug and Alcohol Testing

Science.gov (United States)

2012-02-23

... 199 [Docket No. PHMSA-2011-0335] Pipeline Safety: Post Accident Drug and Alcohol Testing AGENCY... operators of Liquefied Natural Gas (LNG) facilities to conduct post- accident drug and alcohol tests of..., operators must drug and alcohol test each covered employee whose performance either contributed to the...

Experience gained in enhancing operational safety at ComEd`s nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Elias, D [Commonwealth Edison Co. (United States)

1997-09-01

The following aspects of experience gained in enhancing operational safety at Comed`s nuclear power plants are discussed: nuclear safety policy; centralization/decentralization; typical nuclear operating organization; safety review boards; human performance enhancement; elements of effective nuclear oversight.

Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses.

Science.gov (United States)

DeJoy, David M; Smith, Todd D; Woldu, Henok; Dyal, Mari-Amanda; Steege, Andrea L; Boiano, James M

2017-07-01

Antineoplastic drugs pose risks to the healthcare workers who handle them. This fact notwithstanding, adherence to safe handling guidelines remains inconsistent and often poor. This study examined the effects of pertinent organizational safety practices and perceived safety climate on the use of personal protective equipment, engineering controls, and adverse events (spill/leak or skin contact) involving liquid antineoplastic drugs. Data for this study came from the 2011 National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers which included a sample of approximately 1,800 nurses who had administered liquid antineoplastic drugs during the past seven days. Regression modeling was used to examine predictors of personal protective equipment use, engineering controls, and adverse events involving antineoplastic drugs. Approximately 14% of nurses reported experiencing an adverse event while administering antineoplastic drugs during the previous week. Usage of recommended engineering controls and personal protective equipment was quite variable. Usage of both was better in non-profit and government settings, when workers were more familiar with safe handling guidelines, and when perceived management commitment to safety was higher. Usage was poorer in the absence of specific safety handling procedures. The odds of adverse events increased with number of antineoplastic drugs treatments and when antineoplastic drugs were administered more days of the week. The odds of such events were significantly lower when the use of engineering controls and personal protective equipment was greater and when more precautionary measures were in place. Greater levels of management commitment to safety and perceived risk were also related to lower odds of adverse events. These results point to the value of implementing a comprehensive health and safety program that utilizes available hazard controls and effectively communicates

10 Standards for Oversight and Transparency of National Intelligence Services

NARCIS (Netherlands)

Eskens, S.; van Daalen, O.; van Eijk, N.

2016-01-01

This report aims to enhance the policy debate on surveillance by intelligence services by focusing on two key components: oversight and transparency. Both oversight and transparency are essential to devising checks and balances in a way that respects human rights. By offering this concise list of

Trust in the pharmaceutical sector : Analysis of drug safety controversies by means of drug life cycles

NARCIS (Netherlands)

Hernández, J.F.

2015-01-01

Before obtaining a marketing approval, the efficacy and safety profile of drugs is studied in specific populations and under well-controlled circumstances. After marketing approval, the drug is made available and used in ‘real world conditions’, which are known to deviate from the trial setting.

Enabling social listening for cardiac safety monitoring: Proceedings from a drug information association-cardiac safety research consortium cosponsored think tank.

Science.gov (United States)

Seifert, Harry A; Malik, Raleigh E; Bhattacharya, Mondira; Campbell, Kevin R; Okun, Sally; Pierce, Carrie; Terkowitz, Jeffrey; Turner, J Rick; Krucoff, Mitchell W; Powell, Gregory E

2017-12-01

This white paper provides a summary of the presentations and discussions from a think tank on "Enabling Social Listening for Cardiac Safety Monitoring" trials that was cosponsored by the Drug Information Association and the Cardiac Safety Research Consortium, and held at the White Oak headquarters of the US Food and Drug Administration on June 3, 2016. The meeting's goals were to explore current methods of collecting and evaluating social listening data and to consider their applicability to cardiac safety surveillance. Social listening is defined as the act of monitoring public postings on the Internet. It has several theoretical advantages for drug and device safety. First, these include the ability to detect adverse events that are "missed" by traditional sources and the ability to detect adverse events sooner than would be allowed by traditional sources, both by affording near-real-time access to data from culturally and geographically diverse sources. Social listening can also potentially introduce a novel patient voice into the conversation about drug safety, which could uniquely augment understanding of real-world medication use obtained from more traditional methodologies. Finally, it can allow for access to information about drug misuse and diversion. To date, the latter 2 of these have been realized. Although regulators from the Food and Drug Administration and the United Kingdom's Medicines and Healthcare Products Regulatory Agency participated in the think tank along with representatives from industry, academia, and patient groups, this article should not be construed to constitute regulatory guidance. Copyright © 2017 Elsevier Inc. All rights reserved.

Current good manufacturing practice and investigational new drugs intended for use in clinical trials. Final rule.

Science.gov (United States)

2008-07-15

The Food and Drug Administration (FDA) is amending the current good manufacturing practice (CGMP) regulations for human drugs, including biological products, to exempt most phase 1 investigational drugs from complying with the regulatory CGMP requirements. FDA will continue to exercise oversight of the manufacture of these drugs under FDA's general statutory CGMP authority and through review of the investigational new drug applications (IND). In addition, elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document entitled "Guidance for Industry: CGMP for Phase 1 Investigational Drugs" dated November 2007 (the companion guidance). This guidance document sets forth recommendations on approaches to compliance with statutory CGMP for the exempted phase 1 investigational drugs. FDA is taking this action to focus a manufacturer's effort on applying CGMP that is appropriate and meaningful for the manufacture of the earliest stage investigational drug products intended for use in phase 1 clinical trials while ensuring safety and quality. This action will also streamline and promote the drug development process.

Tolerability and safety of antifungal drugs

Directory of Open Access Journals (Sweden)

Francesco Scaglione

2013-08-01

Full Text Available When treating critically ill patients, as those with fungal infections, attention should be focused on the appropriate use of drugs, especially in terms of dose, safety, and tolerability. The fungal infection itself and the concomitant physiological disorders concur to increase the risk of mortality in these patients, therefore the use of any antifungal agent should be carefully evaluated, considering both the direct action on the target fungus and the adverse effects eventually caused. Among antifungal drugs, echinocandins have the greatest tolerability. In fact, unlike amphotericin B, showing nephrotoxicity, and azoles, which are hepatotoxic, the use of echinocandins doesn’t result in major adverse events.http://dx.doi.org/10.7175/rhc.v4i2s.873

Why trash don't pass? pharmaceutical licensing and safety performance of drugs.

Science.gov (United States)

Banerjee, Tannista; Nayak, Arnab

2017-01-01

This paper examines how asymmetric information in pharmaceutical licensing affects the safety standards of licensed drugs. Pharmaceutical companies often license potential drug molecules at different stages of drug development from other pharmaceutical or biotechnology companies and complete the remaining of research stages before submitting the new drug application(NDA) to the food and drug administration. The asymmetric information associated with the quality of licensed molecules might result in the molecules which are less likely to succeed to be licensed out, while those with greater potential of success being held internally for development. We identify the NDAs submitted between 1993 and 2004 where new molecular entities were acquired through licensing. Controlling for other drug area specific and applicant firm specific factors, we investigate whether drugs developed with licensed molecules face higher probability of safety based recall and ultimate withdrawal from the market than drugs developed internally. Results suggest the opposite of Akerlof's (Q J Econ 84:488-500, 1970) lemons problem. Licensed molecules rather have less probability of facing safety based recalls and ultimate withdrawal from the market comparing to internally developed drug molecules. This suggests that biotechnology and small pharmaceutical firms specializing in pharmaceutical research are more efficient in developing good potential molecules because of their concentrated research. Biotechnology firms license out good potential molecules because it increases their market value and reputation. In addition, results suggest that both the number of previous approved drugs in the disease area, and also the applicant firms' total number of previous approvals in all disease areas reduce the probability that an additional approved drug in the same drug area will potentially be harmful.

A primer of drug safety surveillance: an industry perspective. Part II: Product labeling and product knowledge.

Science.gov (United States)

Allan, M C

1992-01-01

To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part II of this series discusses specific issues regarding product labeling, such as developing the labeling, changing the labeling, and the legal as well as commercial ramifications of the contents of the labeling. An adverse event report scenario is further analyzed and suggestions are offered for maintaining the product labeling as an accurate reflection of the drug safety surveillance data. This article also emphasizes the necessity of product knowledge in adverse event database management. Both scientific and proprietary knowledge are required. Acquiring product knowledge is a part of the day-to-day activities of drug safety surveillance. A knowledge of the history of the product may forestall adverse publicity, as shown in the illustration. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction of the components of the process. Suggestions are offered

Observational Pharmacoepidemiology in the Drug Safety and Effectiveness Evaluation

Directory of Open Access Journals (Sweden)

José Cabrita

2017-04-01

Full Text Available Observational epidemiological studies have been used in the medicines context for more than 40 years, contributing to characterize drug use patterns and safety, efficacy and effectiveness profiles. Its use has been increased in recognition of the clinical trials limitations to assess the therapeutic and iatrogenic potential of the medicines after its commercialization. The evolution of the regulatory framework for pharmacovigilance, requiring post-marketing studies, post-authorization safety studies (PASS and the post-authorization efficacy studies (PAES to approve certain drugs, reinforced the importance of observational pharmacoepidemiology for the characterization of the medicines safety and effectiveness profiles. Pharmacoepidemiological research can be carried out from field studies designed to obtain the necessary information or in databases with health records of population samples that already contain the information. This 2nd option is more efficient and more and more frequent. Although, observational research from field studies continues to have its space, the increasing availability of databases allowed a new development to observational pharmacoepidemiology. Indeed, access to automated records databases with up-to-date information on medical prescriptions and global health care to representative population samples with long follow-up periods is a valuable tool for the study of drug use patterns and therapeutic and iatrogenic potential in routine clinical practice. In this context, observational pharmacoepidemiology reinforces its role as a scientific area particularly suitable for evaluating the safety and the effectiveness of the medicines in the “real world”, making a relevant contribution to overcome the gap in translating the evidence from the clinical trials for clinical practice.

Rooting out institutional corruption to manage inappropriate off-label drug use.

Science.gov (United States)

Rodwin, Marc A

2013-01-01

Prescribing drugs for uses that the FDA has not approved - off-label drug use - can sometimes be justified but is typically not supported by substantial evidence of effectiveness. At the root of inappropriate off-label drug use lie perverse incentives for pharmaceutical firms and flawed oversight of prescribing physicians. Typical reform proposals such as increased sanctions for manufacturers might reduce the incidence of unjustified off-label use, but they do not remove the source of the problem. Public policy should address the cause and control the practice. To manage inappropriate off-label drug use, off-label prescriptions must be tracked in order to monitor the risks and benefits and the manufacturers' conduct. Even more important, reimbursement rules should be changed so that manufacturers cannot profit from off-label sales. When off-label sales pass a critical threshold, manufacturers should also be required to pay for independent testing of the safety and effectiveness of off-label drug uses and for the FDA to review the evidence. Manufacturers should also finance, under FDA supervision, programs designed to warn physicians and the public about the risks of off-label drug use. © 2013 American Society of Law, Medicine & Ethics, Inc.

A qualitative phenomenological study: Enhanced, risk-based FAA oversight on part 145 maintenance practices

Science.gov (United States)

Sheehan, Bryan G.

The purpose of this qualitative phenomenological study was to examine the phenomenon of enhanced, risk-based Federal Aviation Administration (FAA) oversight of Part 145 repair stations that performed aircraft maintenance for Part 121 air carriers between 2007 and 2014 in Oklahoma. Specifically, this research was utilized to explore what operational changes have occurred in the domestic Part 145 repair station industry such as variations in management or hiring practices, training, recordkeeping and technical data, inventory and aircraft parts supply-chain logistics, equipment, and facilities. After interviewing 12 managers from Part 145 repair stations in Oklahoma, six major theme codes emerged from the data: quality of oversight before 2007, quality of oversight after 2007, advantages of oversight, disadvantages of oversight, status quo of oversight, and process improvement . Of those six major theme codes, 17 subthemes appeared from the data that were used to explain the phenomenon of enhanced oversight in the Part 145 repair station industry. Forty-two percent of the participants indicated a weak FAA oversight system that has hindered the continuous process improvement program in their repair stations. Some of them were financially burdened after hiring additional full-time quality assurance inspectors to specifically manage enhanced FAA oversight. Notwithstanding, the participants of the study indicated that the FAA must apply its surveillance on a more standardized and consistent basis. They want to see this standardization in how FAA inspectors interpret regulations and practice the same quality of oversight for all repair stations, particularly those that are repeat violators and fail to comply with federal aviation regulations. They believed that when the FAA enforces standardization on a consistent basis, repair stations can become more efficient and safer in the performance of their scope of work for the U.S. commercial air transportation industry.

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

International Nuclear Information System (INIS)

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

2005-03-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2005-03-01

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

76 FR 31416 - Federal Acquisition Regulation; Oversight of Contractor Ethics Programs

Science.gov (United States)

2011-05-31

...-AL92 Federal Acquisition Regulation; Oversight of Contractor Ethics Programs AGENCY: Department of... that contractors have implemented the mandatory contractor business ethics program requirements. DATES... to Improve DoD's Oversight of Contractor Ethics Programs. The ethics program requirement flows from...

76 FR 52231 - Restrictions on Operators Employing Former Flight Standards Service Aviation Safety Inspectors

Science.gov (United States)

2011-08-22

... its implementation of safety management systems, issued its report titled, ``Managing Risks in Civil... Standards Service Aviation Safety Inspectors AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... responsible for the oversight of, a Flight Standards Service Aviation Safety Inspector, and had direct...

75 FR 17417 - Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management...

Science.gov (United States)

2010-04-06

...] Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory... Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee. This meeting was... Drug Safety and Risk Management Advisory Committee would be held on May 12, 2010. On page 10490, in the...

Improvements of the Regulatory Framework for Nuclear Installations in the Areas of Human and Organizational Factors and Safety Culture

International Nuclear Information System (INIS)

Tronea, M.; Ciurea, C.

2016-01-01

The paper presents the development of regulatory requirements in the area of human and organizational factors taking account of the lessons learned from major accidents in the nuclear industry and in particular of the factors that contributed to the Fukushima Daiichi accident and the improvement of the regulatory oversight of nuclear safety culture. New requirements have been elaborated by the National Commission for Nuclear Activities Control (CNCAN) on the nuclear safety policy of licencees for nuclear installations, on independent nuclear safety oversight, on safety conscious work environment and on the assessment of nuclear safety culture. The regulatory process for the oversight of nuclear safety culture within licencees’ organizations operating nuclear installations and the associated procedure and guidelines, based on the IAEA Safety Standards, have been developed in 2010-2011. CNCAN has used the 37 IAEA attributes for a strong safety culture, grouped into five areas corresponding to safety culture characteristics, as the basis for its regulatory guidelines providing support to the reviewers and inspectors, in their routine activities, for recognising and gathering information relevant to safety culture. The safety culture oversight process, procedure and guidelines are in process of being reviewed and revised to improve their effectiveness and to align with the current international practices, using lessons learned from the Fukushima Daiichi accident. Starting with July 2014, Romania has a National Strategy for Nuclear Safety and Security, which includes strategic objectives, associated directions for action and concrete actions for promoting nuclear safety culture in all the organizations in the nuclear sector. The progress with the implementation of this strategy with regard to nuclear safety culture is described in the paper. CNCAN started to define its own organizational culture model and identifying the elements that promote and support safety

ISSUES OF FETUS DRUG SAFETY

Directory of Open Access Journals (Sweden)

A.V. Ostrovskaya

2010-01-01

Full Text Available The article is focused on the issue of fetus drug safety. Development of a child’s health depends both on hereditary information and environment factors. The reason for deviation from the process of normal prenatal development could be any xenobiotics, physical factors and some medications having a pathogenic effect during pregnancy on the embryo and fetus. Due to that, the physician’s preventive work based on the knowledge of embryogenesis processes and critical development periods. Key words: teratogenic action, medications, prenatal development, congenital malformation, newborns, children.(Pediatric Pharmacology. – 2010; 7(1:25-28

The basics of preclinical drug development for neurodegenerative disease indications.

Science.gov (United States)

Steinmetz, Karen L; Spack, Edward G

2009-06-12

Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonization. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and

Role of the Regulatory Body in Implementing Defence in Depth in Nuclear Installations - Regulatory Oversight in Egypt

Energy Technology Data Exchange (ETDEWEB)

El-Sheikh, B. M., E-mail: badawymel@yahoo.com [Egyptian Nuclear and Radiological Regulatory Authority Cairo (Egypt)

2014-10-15

The fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear facilities are operated at all times in an acceptably safe manner including the safe conduct of decommissioning activities. Defence in depth is recognized as one of the fundamental safety principles that underlie the safety of nuclear power plants. Defence in depth is implemented to provide a graded protection against a wide variety of transients, incidents and accidents, including equipment failures and human errors within nuclear power plants and events initiated outside plants. The Regulator Body plays an important role in implementing defence in depth in nuclear installations in the context of a clear allocation of responsibilities with an operating organization. This role starting with setting safety objectives and by its own independent review and technical assessment of the safety justifications provided by the operating organization in addition to safety culture investigating within relevant organizations. This paper briefly reviews this role in normal operation and post accidents, and its effects on overall nuclear safety in nuclear installations with reference to Egyptian regulatory oversight. (author)

Drug safety: Pregnancy rating classifications and controversies.

Science.gov (United States)

Wilmer, Erin; Chai, Sandy; Kroumpouzos, George

2016-01-01

This contribution consolidates data on international pregnancy rating classifications, including the former US Food and Drug Administration (FDA), Swedish, and Australian classification systems, as well as the evidence-based medicine system, and discusses discrepancies among them. It reviews the new Pregnancy and Lactation Labeling Rule (PLLR) that replaced the former FDA labeling system with narrative-based labeling requirements. PLLR emphasizes on human data and highlights pregnancy exposure registry information. In this context, the review discusses important data on the safety of most medications used in the management of skin disease in pregnancy. There are also discussions of controversies relevant to the safety of certain dermatologic medications during gestation. Copyright © 2016 Elsevier Inc. All rights reserved.

48 CFR 52.236-24 - Work Oversight in Architect-Engineer Contracts.

Science.gov (United States)

2010-10-01

... Architect-Engineer Contracts. 52.236-24 Section 52.236-24 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.236-24 Work Oversight in Architect-Engineer Contracts. As prescribed in 36.609-3, insert the following clause: Work Oversight in Architect-Engineer Contracts (APR 1984) The extent and...

Application of the Pareto principle to identify and address drug-therapy safety issues.

Science.gov (United States)

Müller, Fabian; Dormann, Harald; Pfistermeister, Barbara; Sonst, Anja; Patapovas, Andrius; Vogler, Renate; Hartmann, Nina; Plank-Kiegele, Bettina; Kirchner, Melanie; Bürkle, Thomas; Maas, Renke

2014-06-01

Adverse drug events (ADE) and medication errors (ME) are common causes of morbidity in patients presenting at emergency departments (ED). Recognition of ADE as being drug related and prevention of ME are key to enhancing pharmacotherapy safety in ED. We assessed the applicability of the Pareto principle (~80 % of effects result from 20 % of causes) to address locally relevant problems of drug therapy. In 752 cases consecutively admitted to the nontraumatic ED of a major regional hospital, ADE, ME, contributing drugs, preventability, and detection rates of ADE by ED staff were investigated. Symptoms, errors, and drugs were sorted by frequency in order to apply the Pareto principle. In total, 242 ADE were observed, and 148 (61.2 %) were assessed as preventable. ADE contributed to 110 inpatient hospitalizations. The ten most frequent symptoms were causally involved in 88 (80.0 %) inpatient hospitalizations. Only 45 (18.6 %) ADE were recognized as drug-related problems until discharge from the ED. A limited set of 33 drugs accounted for 184 (76.0 %) ADE; ME contributed to 57 ADE. Frequency-based listing of ADE, ME, and drugs involved allowed identification of the most relevant problems and development of easily to implement safety measures, such as wall and pocket charts. The Pareto principle provides a method for identifying the locally most relevant ADE, ME, and involved drugs. This permits subsequent development of interventions to increase patient safety in the ED admission process that best suit local needs.

Enhancing board oversight on quality of hospital care: an agency theory perspective.

Science.gov (United States)

Jiang, H Joanna; Lockee, Carlin; Fraser, Irene

2012-01-01

Community hospitals in the United States are almost all governed by a governing board that is legally accountable for the quality of care provided. Increasing pressures for better quality and safety are prompting boards to strengthen their oversight function on quality. In this study, we aimed to provide an update to prior research by exploring the role and practices of governing boards in quality oversight through the lens of agency theory and comparing hospital quality performance in relation to the adoption of those practices. Data on board practices from a survey conducted by The Governance Institute in 2007 were merged with data on hospital quality drawn from two federal sources that measured processes of care and mortality. The study sample includes 445 public and private not-for-profit hospitals. We used factor analysis to explore the underlying dimensions of board practices. We further compared hospital quality performance by the adoption of each individual board practice. Consistent with the agency theory, the 13 board practices included in the survey appear to center around enhancing accountability of the board, management, and the medical staff. Reviewing the hospital's quality performance on a regular basis was the most common practice. A number of board practices, not examined in prior research, showed significant association with better performance on process of care and/or risk-adjusted mortality: requiring major new clinical programs to meet quality-related criteria, setting some quality goals at the "theoretical ideal" level, requiring both the board and the medical staff to be as involved as management in setting the agenda for discussion on quality, and requiring the hospital to report its quality/safety performance to the general public. Hospital governing boards should examine their current practices and consider adopting those that would enhance the accountability of the board itself, management, and the medical staff.

Corporate social responsibility for nanotechnology oversight.

Science.gov (United States)

Kuzma, Jennifer; Kuzhabekova, Aliya

2011-11-01

Growing public concern and uncertainties surrounding emerging technologies suggest the need for socially-responsible behavior of companies in the development and implementation of oversight systems for them. In this paper, we argue that corporate social responsibility (CSR) is an important aspect of nanotechnology oversight given the role of trust in shaping public attitudes about nanotechnology and the lack of data about the health and environmental risks of nanoproducts. We argue that CSR is strengthened by the adoption of stakeholder-driven models and attention to moral principles in policies and programs. In this context, we examine drivers of CSR, contextual and leadership factors that influence CSR, and strategies for CSR. To illustrate these concepts, we discuss existing cases of CSR-like behavior in nanotechnology companies, and then provide examples of how companies producing nanomedicines can exhibit morally-driven CSR behavior.

Navy Acquisition Executive's Management Oversight and Procurement Authority Category I and II Programs

National Research Council Canada - National Science Library

2007-01-01

.... This report discusses the management oversight and procurement authority within the Navy. Two other reports discussed the management oversight and procurement authority within the Army and Air Force...

Drug research methodology. Volume 4, Epidemiology in drugs and highway safety : the study of drug use among drivers and its role in traffic crashes

Science.gov (United States)

1980-06-01

This report presents the findings of a workshop on epidemiology in drugs and highway safety. A cross-disciplinary panel of experts (1) identified methodological issues and constraints present in research to define the nature and magnitude of the drug...

76 FR 63929 - Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and...

Science.gov (United States)

2011-10-14

...] Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and... Administration (FDA). The meeting will be open to the public. Name of Committees: Drug Safety and Risk Management... Safe Use (ETASU) before its Drug Safety and Risk Management Advisory Committee (DSaRM). On December 1...

Safety risks with investigational drugs: Pharmacy practices and perceptions in the veterans affairs health system.

Science.gov (United States)

Cruz, Jennifer L; Brown, Jamie N

2015-06-01

Rigorous practices for safe dispensing of investigational drugs are not standardized. This investigation sought to identify error-prevention processes utilized in the provision of investigational drug services (IDS) and to characterize pharmacists' perceptions about safety risks posed by investigational drugs. An electronic questionnaire was distributed to an audience of IDS pharmacists within the Veteran Affairs Health System. Multiple facets were examined including demographics, perceptions of medication safety, and standard processes used to support investigational drug protocols. Twenty-one respondents (32.8% response rate) from the Northeast, Midwest, South, West, and Non-contiguous United States participated. The mean number of pharmacist full-time equivalents (FTEs) dedicated to the IDS was 0.77 per site with 0.2 technician FTEs. The mean number of active protocols was 22. Seventeen respondents (81%) indicated some level of concern for safety risks. Concerns related to the packaging of medications were expressed, most notably lack of product differentiation, expiration dating, barcodes, and choice of font size or color. Regarding medication safety practices, the majority of sites had specific procedures in place for storing and securing drug supply, temperature monitoring, and prescription labeling. Repackaging bulk items and proactive error-identification strategies were less common. Sixty-seven percent of respondents reported that an independent double check was not routinely performed. Medication safety concerns exist among pharmacists in an investigational drug service; however, a variety of measures have been employed to improve medication safety practices. Best practices for the safe dispensing of investigational medications should be developed in order to standardize these error-prevention strategies.

Analyzing research trends on drug safety using topic modeling.

Science.gov (United States)

Zou, Chen

2018-04-06

Published drug safety data has evolved in the past decade due to scientific and technological advances in the relevant research fields. Considering that a vast amount of scientific literature has been published in this area, it is not easy to identify the key information. Topic modeling has emerged as a powerful tool to extract meaningful information from a large volume of unstructured texts. Areas covered: We analyzed the titles and abstracts of 4347 articles in four journals dedicated to drug safety from 2007 to 2016. We applied Latent Dirichlet allocation (LDA) model to extract 50 main topics, and conducted trend analysis to explore the temporal popularity of these topics over years. Expert Opinion/Commentary: We found that 'benefit-risk assessment and communication', 'diabetes' and 'biologic therapy for autoimmune diseases' are the top 3 most published topics. The topics relevant to the use of electronic health records/observational data for safety surveillance are becoming increasingly popular over time. Meanwhile, there is a slight decrease in research on signal detection based on spontaneous reporting, although spontaneous reporting still plays an important role in benefit-risk assessment. The topics related to medical conditions and treatment showed highly dynamic patterns over time.

17 CFR 202.11 - Public Company Accounting Oversight Board budget approval process.

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Public Company Accounting Oversight Board budget approval process. 202.11 Section 202.11 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION INFORMAL AND OTHER PROCEDURES § 202.11 Public Company Accounting Oversight...

Legacy data sharing to improve drug safety assessment: the eTOX project

DEFF Research Database (Denmark)

Sanz, Ferran; Pognan, François; Steger-Hartmann, Thomas

2017-01-01

The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through...

Strategic planning of an integrated program for state oversight agreements

International Nuclear Information System (INIS)

Walzer, A.E.; Cothron, T.K.

1991-01-01

Among the barrage of agreements faced by federal facilities are the State Oversight Agreements (known as Agreements in Principle in many states). These agreements between the Department of Energy (DOE) and the states fund the states to conduct independent environmental monitoring and oversight which requires plans, studies, inventories, models, and reports from DOE and its management and operating contractors. Many states have signed such agreements, including Tennessee, Kentucky, Washington, Idaho, Colorado, California, and Florida. This type of oversight agreement originated in Colorado as a result of environmental concerns at the Rocky Flats Plant. The 5-year State Oversight Agreements for Tennessee and Kentucky became effective on May 13, 1991, and fund these states nearly $21 million and $7 million, respectively. Implementation of these open-quotes comprehensive and integratedclose quotes agreements is particularly complex in Tennessee where the DOE Oak Ridge Reservation houses three installations with distinctly different missions. The program development and strategic planning required for coordinating and integrating a program of this magnitude is discussed. Included are the organizational structure and interfaces required to define and coordinate program elements across plants and to also effectively negotiate scope and schedules with the state. The planned Program Management Plan, which will contain implementation and procedural guidelines, and the management control system for detailed tracking of activities and costs are outlined. Additionally, issues inherent in the nature of the agreements and implementation of a program of this magnitude are discussed. Finally, a comparison of the agreements for Tennessee, Kentucky, Colorado, and Idaho is made to gain a better understanding of the similarities and differences in State Oversight Agreements to aid in implementation of these agreements

Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

Science.gov (United States)

Swedberg, Michael D B

2016-01-01

Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit

Regulatory Oversight for New Projects - Challenges and Improvement in Regulation

International Nuclear Information System (INIS)

Lall, F.

2016-01-01

From inception, there has been rise in number of Nuclear Power Plants (NPP) even though very few accidents / events led to intermittent setbacks. However these accidents / events have posed challenges towards enhancement of safety and scope of regulation in all phases of NPP such as siting, design, construction, commissioning and decommissioning. It is essential to ensure compliance to these enhanced safety requirements during all phases of NPP. New and evolutionary reactors are under threshold for regulatory consideration world over. The variety of technologies and genres by themselves pose challenges to regulatory bodies. These challenges are to be addressed through systematic enhancement of the regulation including updating of regulatory documents. The paper touches upon some key elements to be considered towards such enhancement of regulation during all stages of NPP. These being; ensuring quality assurance, regulatory oversight especially over supply chain and contractors, counterfeit material specifically in case of international dealings, emergency handling in case of multi-unit site, feedback and associated enhancements from international events, construction experience database and feedback for safety enhancement, qualification and acceptance of first of a kind systems, regulatory enforcement specifically in case of imported reactors and maintaining interface between safety and security. Regulation in present context has become dynamic and Regulatory bodies need to continue enhancement of its current regulation taking into account the technological developments, feedback from construction, operation and accidents in the current fleet of plants. The paper touches upon some of these elements and highlights the challenges and improvements in regulation. (author)

Nuclear Energy: Compendium of relevant GAO products on regulation, health, and safety

International Nuclear Information System (INIS)

1986-01-01

This report presents findings, conclusions, and recommendations in the areas of (1) protecting worker health and safety, (2) planning for nuclear emergencies and coordinating response mechanisms in the event of a serious nuclear accident, (3) ensuring the safe design of facilities, and (4) monitoring the environment. GAO points out that impaired organizational independence of the oversight function, a lack of headquarters authority, and the decentralized nature of the oversight activities may constitute serious problems over the long term. More recent GAO work indicates that organizational independence of the oversight function may still be a problem area and is likely to receive increased scrutiny in the aftermath of the Chernobyl nuclear reactor accident in the Soviet Union

Biological Select Agents and Toxins: Risk-Based Assessment Management and Oversight.

Energy Technology Data Exchange (ETDEWEB)

Burnett, LouAnn Crawford; Brodsky, Benjamin H.

2016-12-01

Sandia National Laboratories' International Biological and Chemical Threat Reduction (SNL/IBCTR) conducted, on behalf of the Federal Select Agent Program (FSAP), a review of risk assessment in modern select agent laboratories. This review and analysis consisted of literature review, interviews of FSAP staff, entities regulated by FSAP, and deliberations of an expert panel. Additionally, SNL/IBCTR reviewed oversight mechanisms used by industries, US agencies, and other countries for high-consequence risks (e.g, nuclear, chemical, or biological materials, aviation, off-shore drilling, etc.) to determine if alternate oversight mechanisms existed that might be applicable to FSAP oversight of biological select agents and toxins. This report contains five findings, based on these reviews and analyses, with recommendations and suggested actions for FSAP to consider.

Exploiting pluripotent stem cell technology for drug discovery, screening, safety, and toxicology assessments.

Science.gov (United States)

McGivern, Jered V; Ebert, Allison D

2014-04-01

In order for the pharmaceutical industry to maintain a constant flow of novel drugs and therapeutics into the clinic, compounds must be thoroughly validated for safety and efficacy in multiple biological and biochemical systems. Pluripotent stem cells, because of their ability to develop into any cell type in the body and recapitulate human disease, may be an important cellular system to add to the drug development repertoire. This review will discuss some of the benefits of using pluripotent stem cells for drug discovery and safety studies as well as some of the recent applications of stem cells in drug screening studies. We will also address some of the hurdles that need to be overcome in order to make stem cell-based approaches an efficient and effective tool in the quest to produce clinically successful drug compounds. Copyright © 2013 Elsevier B.V. All rights reserved.

75 FR 10507 - Information Security Oversight Office; National Industrial Security Program Policy Advisory...

Science.gov (United States)

2010-03-08

... NATIONAL ARCHIVES AND RECORDS ADMINISTRATION Information Security Oversight Office; National Industrial Security Program Policy Advisory Committee (NISPPAC) AGENCY: National Archives and Records... individuals planning to attend must be submitted to the Information Security Oversight Office (ISOO) no later...

The principle of safety evaluation in medicinal drug - how can toxicology contribute to drug discovery and development as a multidisciplinary science?

Science.gov (United States)

Horii, Ikuo

2016-01-01

Pharmaceutical (drug) safety assessment covers a diverse science-field in the drug discovery and development including the post-approval and post-marketing phases in order to evaluate safety and risk management. The principle in toxicological science is to be placed on both of pure and applied sciences that are derived from past/present scientific knowledge and coming new science and technology. In general, adverse drug reactions are presented as "biological responses to foreign substances." This is the basic concept of thinking about the manifestation of adverse drug reactions. Whether or not toxic expressions are extensions of the pharmacological effect, adverse drug reactions as seen from molecular targets are captured in the category of "on-target" or "off-target", and are normally expressed as a biological defense reaction. Accordingly, reactions induced by pharmaceuticals can be broadly said to be defensive reactions. Recent molecular biological conception is in line with the new, remarkable scientific and technological developments in the medical and pharmaceutical areas, and the viewpoints in the field of toxicology have shown that they are approaching toward the same direction as well. This paper refers to the basic concept of pharmaceutical toxicology, the differences for safety assessment in each stage of drug discovery and development, regulatory submission, and the concept of scientific considerations for risk assessment and management from the viewpoint of "how can multidisciplinary toxicology contribute to innovative drug discovery and development?" And also realistic translational research from preclinical to clinical application is required to have a significant risk management in post market by utilizing whole scientific data derived from basic and applied scientific research works. In addition, the significance for employing the systems toxicology based on AOP (Adverse Outcome Pathway) analysis is introduced, and coming challenges on precision

Drug packaging in 2014: authorities should direct more efforts towards medication safety.

Science.gov (United States)

2015-05-01

In 2014, Prescrire examined the packaging quality of about 250 drugs. A few advances stand out, mainly involving recent drugs, but on the whole, the situation is worrisome in terms of medication safety. Although pharmaceutical companies and drug regulatory agencies seem to be taking more account of the risk of accidental poisoning in children, the level of protection remains low overall in the absence of stringent measures on the part of the authorities. New drugs too often have poor-quality or even dangerous packaging at the time of their market introduction. And the packaging quality of older drugs is disturbing. Pharmaceutical companies no longer invest in the packaging of these products, and agencies often fail to take advantage of the opportunities provided by their reassessment to improve the situation. The inappropriate labelling of certain injectable drugs remains a source of medication errors, sometimes resulting in very serious consequences. In 2014, signs of progress in the packaging of several drugs show that its role in medication safety is better appreciated. But the persistence of dangers in the pharmaceuticals market, created by "unfinished", overly complex or poor-quality packaging, raises the question of the responsibility of pharmaceutical companies and agencies for past and present accidents.

Illegal "no prescription" internet access to narrow therapeutic index drugs.

Science.gov (United States)

Liang, Bryan A; Mackey, Tim K; Lovett, Kimberly M

2013-05-01

Narrow therapeutic index (NTI) drugs, because of proximity of therapeutic amounts to toxic amounts, require close professional oversight, particularly when switching formulations. However, safe use may be compromised by unsupervised switching through access to online "no prescription" Web sites. We assessed no prescription online availability of NTI drugs, using an academically published list (core NTI drugs). Using the Google search term "buy DRUG no prescription," we reviewed the first 5 search result pages for marketing of no prescription NTI drugs. We further assessed if National Association of Boards of Pharmacy (NABP) Not Recommended vendors were marketing NTI drugs. Searches were conducted from November 3, 2012 to January 3, 2013. For core NTI drugs, we found 13 of 14 NTI drugs (92%) marketed as available without prescription, all from NABP Not Recommended vendors. On the basis of these initial findings, we expanded our core list to 12 additional NTI drugs; 11 of 12 of these drugs (92%) were available from no prescription Web sites. Overall, 24 of 26 NTI drugs (92%) were illegally marketed as available online without the need for a prescription. Suspect online NTI drug access from no prescription vendors represents a significant patient safety risk because of potential patient drug switching and risk of counterfeit versions. Further, state health care exchanges with coverage limitations may drive patients to seek formulations online. Food and Drug Administration harmonization with tighter international NTI drug standards should be considered, and aggressive action against suspect online marketers should be a regulatory and public health priority. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Drug safety is a barrier to the discovery and development of new androgen receptor antagonists.

Science.gov (United States)

Foster, William R; Car, Bruce D; Shi, Hong; Levesque, Paul C; Obermeier, Mary T; Gan, Jinping; Arezzo, Joseph C; Powlin, Stephanie S; Dinchuk, Joseph E; Balog, Aaron; Salvati, Mark E; Attar, Ricardo M; Gottardis, Marco M

2011-04-01

Androgen receptor (AR) antagonists are part of the standard of care for prostate cancer. Despite the almost inevitable development of resistance in prostate tumors to AR antagonists, no new AR antagonists have been approved for over a decade. Treatment failure is due in part to mutations that increase activity of AR in response to lower ligand concentrations as well as to mutations that result in AR response to a broader range of ligands. The failure to discover new AR antagonists has occurred in the face of continued research; to enable progress, a clear understanding of the reasons for failure is required. Non-clinical drug safety studies and safety pharmacology assays were performed on previously approved AR antagonists (bicalutamide, flutamide, nilutamide), next generation antagonists in clinical testing (MDV3100, BMS-641988), and a pre-clinical drug candidate (BMS-501949). In addition, non-clinical studies with AR mutant mice, and EEG recordings in rats were performed. Non-clinical findings are compared to disclosures of clinical trial results. As a drug class, AR antagonists cause seizure in animals by an off-target mechanism and are found in vitro to inhibit GABA-A currents. Clinical trials of candidate next generation AR antagonists identify seizure as a clinical safety risk. Non-clinical drug safety profiles of the AR antagonist drug class create a significant barrier to the identification of next generation AR antagonists. GABA-A inhibition is a common off-target activity of approved and next generation AR antagonists potentially explaining some side effects and safety hazards of this class of drugs. Copyright © 2010 Wiley-Liss, Inc.

Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

Science.gov (United States)

Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

2017-11-01

Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

Whistleblower Protection: DOD Needs to Enhance Oversight of Military Whistleblower Reprisal Investigations

Science.gov (United States)

2015-05-01

WHISTLEBLOWER PROTECTION DOD Needs to Enhance Oversight of Military Whistleblower Reprisal Investigations Report...00-2015 to 00-00-2015 4. TITLE AND SUBTITLE Whistleblower Protection: DOD Needs to Enhance Oversight of Military Whistleblower Reprisal...Government Accountability Office Highlights of GAO-15-477, a report to congressional requesters May 2015 WHISTLEBLOWER PROTECTION DOD

The basics of preclinical drug development for neurodegenerative disease indications

Directory of Open Access Journals (Sweden)

Spack Edward G

2009-06-01

Full Text Available Abstract Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA Good Laboratory Practices and international guidelines, including the International Conference on Harmonisation. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s. Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot

Enhancing food safety: the role of the Food and Drug Administration

National Research Council Canada - National Science Library

Wallace, Robert B; Oria, Maria

2010-01-01

.... Food and Drug Administration's abilities to discover potential threats to food safety and prevent outbreaks of foodborne illness are hampered by impediments to efficient use of its limited resources...

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

Science.gov (United States)

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

2018-06-01

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

Improving MC and A Oversight in Russia by Implementing Measurement and Training Programs

International Nuclear Information System (INIS)

Bokov, Dmitry; Byers, Kenneth R.

2004-01-01

As the Russian State regulatory agency responsible for oversight of nuclear material control and accounting (MC and A), Gosatomnadzor of Russia (GAN) determines the status of the MC and A programs at Russian facilities. Last year, GAN developed and implemented their Nuclear Material Measurement Program Plan which documents current non-destructive assay (NDA) measurement capability in all regions of GAN; provides justification for upgrades to equipment, procedures and training; and defines the inspector-facility operator interface as it relates to NDA measurement equipment use. This Program Plan has helped to give the GAN inspection measurements more legal and official status as an oversight tool, and has also helped to improve other GAN MC and A oversight activities. These improvements include developing a tamper-indicating device program, conducting NDA workshops at specific Russian nuclear facilities to better train MC and A inspectors, and developing training evaluation programs. The Program is an important tool to address the GAN role in oversight of the Russian Federal Information System nuclear material database. This paper describes the feedback received from the GAN regional offices on the implementation of the Program Plan during its first year in operation and how the Program Plan has affected other GAN inspection activities to improve MC and A oversight.

Comparison of the safety information on drug labels in three developed countries: The USA, UK and Canada

Directory of Open Access Journals (Sweden)

Thamir M. Alshammari

2017-12-01

Full Text Available The safety information on drug labels of a company marketing the same drugs in different countries is sometimes different. The aim of the present study is to understand the differences in the volume and content of safety information on the drug labels from the same manufacturers in three developed countries: the United States of America (USA, the United Kingdom (UK and Canada. This study involved the calculation of the proportion of total safety information (PSI and of contraindications (PCI in comparison to all information on the label and the percentage of boxed warnings (PBW among the 100 labels studied from each country. The PSI on the labels of different countries is different with USA labels bearing lesser value PSI and UK labels bearing higher value PSI. The qualitative information provided on these drug labels from each country in ‘contraindications’ sections, ‘boxed/serious warnings’ and ‘overdosage’ sections presented differences in the information provided on most of the labels. We have found distinct differences between the safety information available on drug labels in terms of volume and content. We conclude that the safety information for the same products should be standardised across all countries.

Perspectives on dam safety in Canada

International Nuclear Information System (INIS)

Halliday, R.

2004-01-01

Canadian dam safety issues were reviewed from the perspective of a water resources engineer who is not a dam safety practitioner. Several external factors affecting dam safety were identified along with perceived problems in dam safety administration. The author claims that the main weakness in safety practices can be attributed to provincial oversights and lack of federal engagement. Some additions to the Canadian Dam Safety Guidelines were proposed to address these weaknesses. Canada has hundreds of large dams and high hazard dams whose failure would result in severe downstream consequences. The safety of dams built on boundary waters shared with the United States have gained particular attention from the International Joint Commission. This paper also examined safety criteria for concerns such as aging dams, sabotage and global climate change that may compromise the safety of a dam. 26 refs

The Expected Net Present Value of Developing Weight Management Drugs in the Context of Drug Safety Litigation.

Science.gov (United States)

Chawla, Anita; Carls, Ginger; Deng, Edmund; Tuttle, Edward

2015-07-01

Following withdrawals, failures, and significant litigation settlements, drug product launches in the anti-obesity category slowed despite a large and growing unmet need. Litigation concerns, a more risk-averse regulatory policy, and the difficulty of developing a product with a compelling risk-benefit profile in this category may have limited innovators' expected return on investment and restricted investment in this therapeutic area. The objective of the study was to estimate perceived manufacturer risk associated with product safety litigation and increased development costs vs. revenue expectations on anticipated return on investment and to determine which scenarios might change a manufacturer's investment decision. Expected net present value of a weight-management drug entering pre-clinical trials was calculated for a range of scenarios representing evolving expectations of development costs, revenue, and litigation risk over the past 25 years. These three factors were based on published estimates, historical data, and analogs from other therapeutic areas. The main driver in expected net present value calculations is expected revenue, particularly if one assumes that litigation risk and demand are positively correlated. Changes in development costs associated with increased regulatory concern with potential safety issues for the past 25 years likely did not impact investment decisions. Regulatory policy and litigation risk both played a role in anti-obesity drug development; however, product revenue-reflecting efficacy at acceptable levels of safety-was by far the most important factor. To date, relatively modest sales associated with recent product introductions suggest that developing a product that is sufficiently efficacious with an acceptable level of safety continues to be the primary challenge in this market.

Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study

Energy Technology Data Exchange (ETDEWEB)

Nabili, Marjan, E-mail: mnabili@gwmail.gwu.edu [Department of Electrical and Computer Engineering, The George Washington University, 800 22nd Street NW, Room 5000, Washington, DC 20052 (United States); Geist, Craig, E-mail: cgeist@mfa.gwu.edu, E-mail: zderic@gwu.edu [Department of Ophthalmology, The George Washington University, 2150 Pennsylvania Avenue NW, Floor 2A, Washington, DC 20037 (United States); Zderic, Vesna, E-mail: cgeist@mfa.gwu.edu, E-mail: zderic@gwu.edu [Department of Biomedical Engineering, The George Washington University, 800 22nd Street NW, Room 6670, Washington, DC 20052 (United States)

2015-10-15

Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors’ previous in vitro and in vivo studies. Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications of different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz–1 MHz, intensities of 0.3–1 W/cm{sup 2}, and exposure duration of 5 min, which were the parameters used in the authors’ previous drug delivery experiments. The baseline eye temperature was 37 °C. Results: The authors’ results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. Conclusions: The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm{sup 2} (parameters shown in the authors’ previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety

Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study

International Nuclear Information System (INIS)

Nabili, Marjan; Geist, Craig; Zderic, Vesna

2015-01-01

Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors’ previous in vitro and in vivo studies. Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications of different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz–1 MHz, intensities of 0.3–1 W/cm 2 , and exposure duration of 5 min, which were the parameters used in the authors’ previous drug delivery experiments. The baseline eye temperature was 37 °C. Results: The authors’ results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. Conclusions: The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm 2 (parameters shown in the authors’ previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety of this

Institutional Oversight of Faculty-Industry Consulting Relationships in U.S. Medical Schools: A Delphi Study.

Science.gov (United States)

Morain, Stephanie R; Joffe, Steven; Campbell, Eric G; Mello, Michelle M

2015-01-01

The conflicts of interest that may arise in relationships between academic researchers and industry continue to prompt controversy. The bulk of attention has focused on financial aspects of these relationships, but conflicts may also arise in the legal obligations that faculty acquire through consulting contracts. However, oversight of faculty members' consulting agreements is far less vigorous than for financial conflicts, creating the potential for faculty to knowingly or unwittingly contract away important rights and freedoms. Increased regulation could prevent this, but it is unclear what forms of oversight universities view as feasible and effective. In this article, we report on a Delphi study to evaluate several approaches for oversight of consulting agreements by medical schools. The panel was comprised of 11 senior administrators with responsibility for oversight of faculty consulting relationships. We found broad agreement among panelists regarding the importance of institutional oversight to protect universities' interests. There was strong support for two specific approaches: providing educational resources to faculty and submitting consulting agreements for institutional review. Notwithstanding the complexities of asserting authority to regulate private consulting agreements between faculty members and companies, medical school administrators reached consensus that several approaches to improving institutional oversight are feasible and useful. © 2015 American Society of Law, Medicine & Ethics, Inc.

[Evaluation of the safety of innovative drugs against viruses and infectious agents].

Science.gov (United States)

Kobayashi, Tetsu; Yusa, Keisuke; Kawasaki, Nana

2013-01-01

Recently, several novel cellular therapy products and biological drugs are being developed to treat various previously untreatable diseases. One of the most important issues regarding these innovations is how to ensure safety over infectious agents, including viruses and prions, in the earliest treatments with these products. The object of this study is a risk assessment of cases of human infectious with the agents and to present a sample risk management plan based on a collaboration among the National Institute of Health Sciences, universities, marketing authorization holders, and scientific societies. There are three subjects of study: (1) the viral safety of cellular therapy products, (2) the viral safety of biological drugs, and (3) the safety of prions. In this report, we describe the objects of the study, the project members, the study plan outline, and the ongoing plans. The results of the viral risk identification and the risk analysis of cellular therapy products will also be described, based on a review of the literature and case reports obtained during the first year of this project.

Assessment of pharmacovigilance approaches for monitoring the safety of antimalarial drugs in pregnancy

NARCIS (Netherlands)

Dellicour, S.O.M.C.

2014-01-01

Post-marketing surveillance of drugs used in pregnancy is challenging, especially in developing countries where resources for pharmacovigilance are rare. There is a need to establish simple but effective systems to monitor safety of drugs given during pregnancy in resource constrained countries.

Does nanobiotechnology oversight present a uniquely complex challenge to interagency cooperation?

International Nuclear Information System (INIS)

Karkkainen, Bradley C.

2011-01-01

Numerous regulatory and oversight challenges exist in the field of nanobiotechnology. Although these challenges may appear novel and complex, similar issues have plagued environmental regulation since the 1970 s. This article argues that complexity, uncertainty, and regulatory gaps are common problems in environmental regulation, and that the lessons learned and progress made during more than 40 years of environmental regulation can serve as a guidepost for addressing nanobiotechnology regulation and oversight issues.

Integrated safety analysis of rolapitant with coadministered drugs from phase II/III trials

DEFF Research Database (Denmark)

Barbour, S; Smit, T.; Wang, X

2017-01-01

adverse events by use versus non-use of drug substrates of CYP2D6 or BCRP. Patients and methods: Patients were randomized to receive either 180 mg oral rolapitant or placebo approximately 1-2 hours before chemotherapy in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Data...... cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To analyze potential drug-drug interactions between rolapitant and concomitant medications, this integrated safety analysis of four double-blind, randomized phase II or III studies of rolapitant examined...... for treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) during cycle 1 were pooled across the four studies and summarized in the overall population and by concomitant use/non-use of CYP2D6 or BCRP substrate drugs. Results: In the integrated safety population, 828...

Recommendations for Nanomedicine Human Subjects Research Oversight: An Evolutionary Approach for an Emerging Field

Science.gov (United States)

Fatehi, Leili; Wolf, Susan M.; McCullough, Jeffrey; Hall, Ralph; Lawrenz, Frances; Kahn, Jeffrey P.; Jones, Cortney; Campbell, Stephen A.; Dresser, Rebecca S.; Erdman, Arthur G.; Haynes, Christy L.; Hoerr, Robert A.; Hogle, Linda F.; Keane, Moira A.; Khushf, George; King, Nancy M.P.; Kokkoli, Efrosini; Marchant, Gary; Maynard, Andrew D.; Philbert, Martin; Ramachandran, Gurumurthy; Siegel, Ronald A.; Wickline, Samuel

2015-01-01

The nanomedicine field is fast evolving toward complex, “active,” and interactive formulations. Like many emerging technologies, nanomedicine raises questions of how human subjects research (HSR) should be conducted and the adequacy of current oversight, as well as how to integrate concerns over occupational, bystander, and environmental exposures. The history of oversight for HSR investigating emerging technologies is a patchwork quilt without systematic justification of when ordinary oversight for HSR is enough versus when added oversight is warranted. Nanomedicine HSR provides an occasion to think systematically about appropriate oversight, especially early in the evolution of a technology, when hazard and risk information may remain incomplete. This paper presents the consensus recommendations of a multidisciplinary, NIH-funded project group, to ensure a science-based and ethically informed approach to HSR issues in nanomedicine, and integrate HSR analysis with analysis of occupational, bystander, and environmental concerns. We recommend creating two bodies, an interagency Human Subjects Research in Nanomedicine (HSR/N) Working Group and a Secretary’s Advisory Committee on Nanomedicine (SAC/N). HSR/N and SAC/N should perform 3 primary functions: (1) analysis of the attributes and subsets of nanomedicine interventions that raise HSR challenges and current gaps in oversight; (2) providing advice to relevant agencies and institutional bodies on the HSR issues, as well as federal and federal-institutional coordination; and (3) gathering and analyzing information on HSR issues as they emerge in nanomedicine. HSR/N and SAC/N will create a home for HSR analysis and coordination in DHHS (the key agency for relevant HSR oversight), optimize federal and institutional approaches, and allow HSR review to evolve with greater knowledge about nanomedicine interventions and greater clarity about attributes of concern. PMID:23289677

MO-AB-201-00: Radiation Safety Officer Update

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-06-15

The role of the Radiation Safety Officer at a medical facility can be complicated. The complexity of the position is based on the breadth of services provided at the institution and the nature of the radioactive materials license. Medical practices are constantly changing and the use of ionizing radiation continues to rise in this area. Some of the newer medical applications involving radiation have unique regulatory and safety issues that must be addressed. Oversight of the uses of radiation start at the local level (radiation safety officer, radiation safety committee) and are heavily impacted by outside agencies (i.e. Nuclear Regulatory Commission, State Radiologic Health, The Joint Commission (TJC), etc). This session will provide both an overview of regulatory oversight and essential compliance practices as well as practical ways to assess and introduce some of the new applications utilizing radioactive materials into your medical facility. Learning Objectives: Regulatory Compliance and Safety with New Radiotherapies: Spheres and Ra-223 (Lance Phillips) Understand the radioactive materials license amendment process to add new radiotherapies (i.e., SIR-Spheres, Therasphere, Xofigo). Understand the AU approval process for microspheres and Xofigo. Examine the training and handling requirements for new procedures. Understand the process involved with protocol development, SOP in order to define roles and responsibilities. The RSO and The RSC: Challenges and Opportunities (Colin Dimock) Understand how to form an effective Committee. Examine what the Committee does for the Program and the RSO. Understand the importance of Committee engagement. Discuss the balance of the complimentary roles of the RSO and the Committee. The Alphabet Soup of Regulatory Compliance: Being Prepared for Inspections (Linda Kroger) Recognize the various regulatory bodies and organizations with oversight or impact in Nuclear Medicine, Radiology and Radiation Oncology. Examine 10CFR35

MO-AB-201-00: Radiation Safety Officer Update

International Nuclear Information System (INIS)

2015-01-01

The role of the Radiation Safety Officer at a medical facility can be complicated. The complexity of the position is based on the breadth of services provided at the institution and the nature of the radioactive materials license. Medical practices are constantly changing and the use of ionizing radiation continues to rise in this area. Some of the newer medical applications involving radiation have unique regulatory and safety issues that must be addressed. Oversight of the uses of radiation start at the local level (radiation safety officer, radiation safety committee) and are heavily impacted by outside agencies (i.e. Nuclear Regulatory Commission, State Radiologic Health, The Joint Commission (TJC), etc). This session will provide both an overview of regulatory oversight and essential compliance practices as well as practical ways to assess and introduce some of the new applications utilizing radioactive materials into your medical facility. Learning Objectives: Regulatory Compliance and Safety with New Radiotherapies: Spheres and Ra-223 (Lance Phillips) Understand the radioactive materials license amendment process to add new radiotherapies (i.e., SIR-Spheres, Therasphere, Xofigo). Understand the AU approval process for microspheres and Xofigo. Examine the training and handling requirements for new procedures. Understand the process involved with protocol development, SOP in order to define roles and responsibilities. The RSO and The RSC: Challenges and Opportunities (Colin Dimock) Understand how to form an effective Committee. Examine what the Committee does for the Program and the RSO. Understand the importance of Committee engagement. Discuss the balance of the complimentary roles of the RSO and the Committee. The Alphabet Soup of Regulatory Compliance: Being Prepared for Inspections (Linda Kroger) Recognize the various regulatory bodies and organizations with oversight or impact in Nuclear Medicine, Radiology and Radiation Oncology. Examine 10CFR35

A perspective on the safety of cosmetic products: a position paper of the American Council on Science and Health.

Science.gov (United States)

Ross, Gilbert

2006-01-01

Over the years, some activist groups have targeted cosmetics as possible human health threats, claiming that cosmetic ingredients are not adequately tested for safety and may pose risks to consumers. The groups allege that industry practices related to safety testing are flawed, that there is little government oversight, and that cosmetics contain cancer-causing chemicals and other toxicants. A critical review of the scientific data related to these claims indicates the following: (1) Industry has the primary responsibility to ensure that all ingredients, preservatives, and coformulants used in products are safe for their intended uses. (2) The U.S. Food and Drug Administration (FDA) has regulatory oversight of the cosmetic industry. Its authority includes the banning or restriction of ingredients for safety reasons. (3) The Cosmetic Ingredient Review (CIR), an independent, scientific review board, critically evaluates chemical ingredients used in cosmetics and publishes the results of its findings in the peer-reviewed literature. (4) Health-related allegations about cosmetic ingredients are generally based on the results of high-dose laboratory testing in animals and have little relevance for humans. As true now as when Paracelsus said it in the 16th century, "It is the dose that makes the poison." (5) The health-related allegations involving specific chemicals (e.g., phthalates, parabens, and 1,3-butadiene) fail to consider important scientific studies and recent regulatory conclusions about these chemicals, which have found that they are not hazardous. (6) Animal and human physiology differ in crucial ways, further invalidating simplistic attempts to extrapolate rodent testing to human health risks. The cosmetic industry should be encouraged to publish more of its toxicity studies and safety evaluations, which would aid in dispelling the uncertainty that some consumers have about cosmetic safety.

Management Oversight and Risk Tree (MORT): a new system safety program

International Nuclear Information System (INIS)

Clark, J.L.

Experiences of Aerojet Nuclear Company (ANC), in the development and implementation of a system safety program for ANC and for the Energy Research and Development Administration (ERDA) are discussed. Aerojet Nuclear is the prime operating contractor for ERDA, formerly AEC, at the Idaho National Engineering Laboratory. The ERDA sponsored ''MORT'' system safety program is described along with the process whereby formal system safety methods are incorporated into a stable organization. Specifically, a discussion is given of initial development of MORT; pilot program trials conducted at ANC; implementation methodology; and reaction of the ANC organization. (auth)

Research on Integration of NPP Operational Safety Management Performance Systems

International Nuclear Information System (INIS)

Chi, Miao; Shi, Liping

2014-01-01

The operational safety management of Nuclear Power Plants demands systematic planning and integrated control. NPPs are following the well-developed safety indicator systems proposed by IAEA Operational Safety Performance Indicator Programme, NRC Reactor Oversight Process or the other institutions. Integration of the systems is proposed to benefiting from the advantages of both systems and avoiding improper application into the real world. The authors analyzed the possibility and necessity for system integration, and propose an indicator system integrating method

Parliamentary Oversight of European Security and Defence Policy: A Matter of Formal Competences or the Will of Parliamentarians?

OpenAIRE

Maatsch, A.; Galella, P.

2016-01-01

Are parliaments with strong formal powers for the deployment of troops likely to conduct more intensive oversight than their counterparts with weak or no powers? The literature suggests that strong formal powers delineate boundaries of parliamentary oversight. However, this article demonstrates that strong formal powers are not necessary for parliaments in order to conduct oversight. If parliaments with weak formal powers had strong incentives to carry out oversight of the EU NAVFOR Operation...

The Patient's Voice in Pharmacovigilance: Pragmatic Approaches to Building a Patient-Centric Drug Safety Organization.

Science.gov (United States)

Smith, Meredith Y; Benattia, Isma

2016-09-01

Patient-centeredness has become an acknowledged hallmark of not only high-quality health care but also high-quality drug development. Biopharmaceutical companies are actively seeking to be more patient-centric in drug research and development by involving patients in identifying target disease conditions, participating in the design of, and recruitment for, clinical trials, and disseminating study results. Drug safety departments within the biopharmaceutical industry are at a similar inflection point. Rising rates of per capita prescription drug use underscore the importance of having robust pharmacovigilance systems in place to detect and assess adverse drug reactions (ADRs). At the same time, the practice of pharmacovigilance is being transformed by a host of recent regulatory guidances and related initiatives which emphasize the importance of the patient's perspective in drug safety. Collectively, these initiatives impact the full range of activities that fall within the remit of pharmacovigilance, including ADR reporting, signal detection and evaluation, risk management, medication error assessment, benefit-risk assessment and risk communication. Examples include the fact that manufacturing authorization holders are now expected to monitor all digital sources under their control for potential reports of ADRs, and the emergence of new methods for collecting, analysing and reporting patient-generated ADR reports for signal detection and evaluation purposes. A drug safety department's ability to transition successfully into a more patient-centric organization will depend on three defining attributes: (1) a patient-centered culture; (2) deployment of a framework to guide patient engagement activities; and (3) demonstrated proficiency in patient-centered competencies, including patient engagement, risk communication and patient preference assessment. Whether, and to what extent, drug safety departments embrace the new patient-centric imperative, and the methods and

Reinventing oversight in the twenty-first century: the question of capacity

International Nuclear Information System (INIS)

Bosso, Christopher; DeLeo, Rob A.; Kay, W. D.

2011-01-01

This article addresses a key question emerging from this project based at the University of Minnesota: the fundamental capacity of government to engage in “dynamic oversight” of emergent technologies. This conception of oversight requires additional or new types of capacity for government agencies that must arbitrate conflicts and endow any outcomes with necessary democratic legitimacy. Rethinking oversight thus also requires consideration of the fundamental design and organizational capacity of the regulatory regime in the democratic state.

Creating a Learning Organization in Law Enforcement: Maturity Levels for Police Oversight Agencies

Science.gov (United States)

Filstad, Cathrine; Gottschalk, Petter

2010-01-01

Purpose: The purpose of this paper is to conceptualize a stage model for maturity levels for police oversight agencies. Design/methodology/approach: The paper is based on a literature review covering police oversight organizations and stages of growth models. Findings: As a conceptual paper, the main findings are related to the appropriateness of…

Prescription for antibiotics at drug shops and strategies to improve quality of care and patient safety

DEFF Research Database (Denmark)

Mbonye, Anthony K; Buregyeya, Esther; Rutebemberwa, Elizeus

2016-01-01

OBJECTIVES: The main objective of this study was to assess practices of antibiotic prescription at registered drug shops with a focus on upper respiratory tract infections among children in order to provide data for policy discussions aimed at improving quality of care and patient safety......-line drug for treatment of pneumonia in children according to the guidelines. CONCLUSIONS: There is urgent need to regulate drug shop practices of prescribing and selling antibiotics, for the safety of patients seeking care at these outlets....

22 CFR 96.32 - Internal structure and oversight.

Science.gov (United States)

2010-04-01

... Accreditation and Approval Licensing and Corporate Governance § 96.32 Internal structure and oversight. (a) The... number of such other provider; and (3) The name, address, and phone number of any entity it uses or...

Transparency and Oversight in Local Wellness Policies

Science.gov (United States)

Chriqui, Jamie F.; Chaloupka, Frank J.

2011-01-01

Background: Advocates have called for increased wellness policy transparency and oversight through the use of health advisory councils. This study examines (1) wellness policy transparency, (2) advisory council requirements, (3) factors associated with each, and (4) whether transparency or advisory council requirements are indicative of a stronger…

Advice on drug safety in pregnancy: are there differences between commonly used sources of information?

Science.gov (United States)

Frost Widnes, Sofia K; Schjøtt, Jan

2008-01-01

Safety regarding use in pregnancy is not established for many drugs. Inconsistencies between sources providing drug information can give rise to confusion with possible therapeutic consequences. Therefore, it is important to measure clinically important differences between drug information sources. The objective of this study was to compare two easily accessible Norwegian sources providing advice on drug safety in pregnancy - the product monographs in the Felleskatalog (FK), published by the pharmaceutical companies, and the five regional Drug Information Centres (DICs) in Norway - in addition to assessing the frequency of questions regarding drug safety in pregnancy made to the DICs according to the Anatomical Therapeutic Chemical (ATC) classification system. Advice on drug use in pregnancy provided by the DICs in 2003 and 2005 were compared with advice in the product monographs for the respective drugs in the FK. Comparison of advice was based on categorization to one of four categories: can be used, benefit-risk assessment, should not be used, or no available information. A total of 443 drug advice were categorized. Seven out of ten of drugs frequently enquired about, according to the ATC system, were drugs acting on the nervous system (group N). For 208 (47%) of the drugs, advice differed between the DICs and FK. Advice from the FK was significantly (p drugs that were newly introduced and those that had been on the market for a longer time, advice regarding use of drugs in the first trimester and advice regarding use of drugs in the second or third trimester, or between advice provided during 2003 and during 2005. The results of this study show considerable differences between two Norwegian sources providing advice on the use of drugs in pregnancy. Based on the knowledge that healthcare providers choose sources of information in a random manner, our results may be of clinical importance. We believe that the problem with heterogeneous drug information on this

17 CFR 201.440 - Appeal of determinations by the Public Company Accounting Oversight Board.

Science.gov (United States)

2010-04-01

... and Commission Review § 201.440 Appeal of determinations by the Public Company Accounting Oversight... for registration of a public accounting firm, may file an application for review. (b) Procedure. An... the Public Company Accounting Oversight Board. 201.440 Section 201.440 Commodity and Securities...

32 CFR 2400.19 - Declassification by the Director of the Information Security Oversight Office.

Science.gov (United States)

2010-07-01

... Information Security Oversight Office. 2400.19 Section 2400.19 National Defense Other Regulations Relating to... SCIENCE AND TECHNOLOGY POLICY INFORMATION SECURITY PROGRAM Declassification and Downgrading § 2400.19 Declassification by the Director of the Information Security Oversight Office. If the Director of the Information...

76 FR 64354 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

Science.gov (United States)

2011-10-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA). In particular...

76 FR 45818 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

Science.gov (United States)

2011-08-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... burden of fee amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA...

13 CFR 120.1070 - Lender oversight fees.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Lender oversight fees. 120.1070 Section 120.1070 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Risk-Based... Lender” means a Small Business Lending Company or a Non-Federally Regulated Lender. (2) On-site reviews...

Nuclear safety in perspective

International Nuclear Information System (INIS)

Andersson, K.; Sjoeberg, B.M.D.; Lauridsen, K.; Wahlstroem, B.

2002-06-01

The aim of the NKS/SOS-1 project has been to enhance common understanding about requirements for nuclear safety by finding improved means of communicating on the subject in society. The project, which has been built around a number of seminars, was supported by limited research in three sub-projects: 1) Risk assessment, 2) Safety analysis, and 3) Strategies for safety management. The report describes an industry in change due to societal factors. The concepts of risk and safety, safety management and systems for regulatory oversight are described in the nuclear area and also, to widen the perspective, for other industrial areas. Transparency and public participation are described as key elements in good risk communication, and case studies are given. Environmental Impact Assessment and Strategic Environmental Assessment are described as important overall processes within which risk communication can take place. Safety culture, safety indicators and quality systems are important concepts in the nuclear safety area are very useful, but also offer important challenges for the future. They have been subject to special attention in the project. (au)

Safety and efficacy of generic drugs with respect to brand formulation

OpenAIRE

Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

2013-01-01

Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to gener...

Safety and efficacy of generic drugs with respect to brand formulation.

Science.gov (United States)

Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

2013-12-01

Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to generic formulations. In conclusion, the use of generic drugs could be related with an increased days of disease (time to relapse) or might lead to a therapeutic failure; on the other hand, a higher drug concentration might expose patients to an increased risk of dose-dependent side-effects.

Type I error probability spending for post-market drug and vaccine safety surveillance with binomial data.

Science.gov (United States)

Silva, Ivair R

2018-01-15

Type I error probability spending functions are commonly used for designing sequential analysis of binomial data in clinical trials, but it is also quickly emerging for near-continuous sequential analysis of post-market drug and vaccine safety surveillance. It is well known that, for clinical trials, when the null hypothesis is not rejected, it is still important to minimize the sample size. Unlike in post-market drug and vaccine safety surveillance, that is not important. In post-market safety surveillance, specially when the surveillance involves identification of potential signals, the meaningful statistical performance measure to be minimized is the expected sample size when the null hypothesis is rejected. The present paper shows that, instead of the convex Type I error spending shape conventionally used in clinical trials, a concave shape is more indicated for post-market drug and vaccine safety surveillance. This is shown for both, continuous and group sequential analysis. Copyright © 2017 John Wiley & Sons, Ltd.

Ideal Police Oversight and Review: The Next Piece of the Community Policing Puzzle

Science.gov (United States)

2015-12-01

oversight. Included in that malpractice are instances of perceived physical and verbal abuse , perceived harassment, failure to take appropriate action...a kid from south Stockton. 1 I. INTRODUCTION A. PROBLEM STATEMENT—BACKGROUND Independent oversight boards are asked to make the complaint...communities with inclusion and investigative transparency when filing complaints of police misconduct and abuse of police powers. In his article “Race

Documentation of pediatric drug safety in manufacturers' product monographs: a cross-sectional evaluation of the canadian compendium of pharmaceuticals and specialities.

Science.gov (United States)

Uppal, Navjeet K; Dupuis, Lee L; Parshuram, Christopher S

2008-01-01

To describe the provision of pediatric drug safety information in a national formulary of manufacturers' drug product monographs. We performed a cross-sectional evaluation of comprehensive product monographs contained in the 2005 Canadian Compendium of Pharmaceuticals and Specialities (CPS). We abstracted data describing indications for prescription, statements about pediatric safety, available preparations, and provision of dosing guidelines. For each monograph we classified pediatric safety data as either present, present but limited or absent. We then described the pediatric safety data in CPS monographs for drugs listed in the published formulary of the Hospital for Sick Children, Toronto, Ontario, Canada. A total of 2232 product monographs were screened; 684 were excluded and 1548 (66%) were further analyzed. 1462 (94%) had indications that did not exclude children. Pediatric safety information was present in 592 (38%), present but limited in 148 (10%), and absent in 808 (52%) drug monographs. Safety statements were absent in 224 (14%) drug monographs that provided both dosing guidelines and formulations suitable for administration to children, and in 214 (52%) of 411 drugs in the pediatric hospital formulary. We evaluated a widely available national source of pediatric prescribing information. Safety data for children was not mentioned in more than half of the product monographs. Moreover, the provision of safety data was discordant with indications for prescription, the availability of pediatric formulations, and dosing guidelines within the monographs, and with inclusion in a pediatric hospital formulary. Our study suggests that the presentation of pediatric safety data in drug product monographs can be improved to better inform prescribing and to optimize pharmacotherapy in children.

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: myocardial and infectious adverse reactions as application cases.

Science.gov (United States)

Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

2015-02-13

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure-activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

Restart oversight assessment of Hanford 242-A evaporator: Summary report

International Nuclear Information System (INIS)

1994-08-01

This report summarizes a January 17--28, 1994, oversight assessment of restart activities for the 242-A Evaporator at the US Department of Energy's (DOE's) Hanford Site about 25 miles northeast of Hanford, Washington. The assessment was conducted by qualified staff and consultants from the DOE Office of Environment, Safety and Health (EH). Its focus was the readiness of the facility for the resumption of safe operations, in particular those operations involved in the treatment and disposal of condensate from the evaporation of liquid radioactive waste, a key element of the tank waste remediation project administered by the DOE Richland Operations Office (DOE-RL). Overall, the assessment yielded eight programmatic concerns, supported by 38 individual findings. Of the concerns, four have already been closed, and the other four have been resolved. Results pointed up strengths in management and engineering design, as well as effective support of facility training programs by the management and operating contractor, Westinghouse Hanford Company (WHC). Weaknesses were evident, however, in conduct of operations, maintenance, and radiological practices. Furthermore, problems in the submittal and approval of Compliance Schedule Approvals--that is, WHC documentation of the status of compliance with DOE orders--were indicative of a programmatic breakdown in the DOE Order compliance process. According to the results of this assessment, there are no safety and health issues that would preclude or delay restart of the evaporator

Short course on system safety analysis

International Nuclear Information System (INIS)

Sudmann, R.H.

1992-01-01

This course provides and introduction to methods generally used in safety analysis and accident investigation. It is a non-mathematical approach, directed toward a casual user. The participant will learn techniques allowing them to dissect a system or incident in order identify real or potential safety problems. These techniques will be applied to analyze events which have occurred within DOE facilities. As a manager or staff person with general oversight responsibilities, the participant should gain an awareness of the big picture and not just ''dig for facts.'' This can be accomplished by being alert and responsive to the atmosphere and condition of the plant; mood and impression of the worker and the behavioral climate. The techniques taught in the course can be used to identify critical areas or indicators. These indicators will signal problems before the ''facts'' will. Analysis techniques taught are used to gauge the breadth of the ''forest'' and not necessarily to identify the trees. For this course includes a technical background with experience in a chemical processing operations and a knowledge of basic chemistry and engineering is desirable. The course should help in a present or future assignment in an oversight role

78 FR 71036 - Pipeline Safety: Random Drug Testing Rate; Contractor Management Information System Reporting...

Science.gov (United States)

2013-11-27

... PHMSA-2013-0248] Pipeline Safety: Random Drug Testing Rate; Contractor Management Information System Reporting; and Obtaining Drug and Alcohol Management Information System Sign-In Information AGENCY: Pipeline... Management Information System (MIS) Data; and New Method for Operators to Obtain User Name and Password for...

Regulatory oversight report 2008 concerning nuclear safety in Swiss nuclear installations

International Nuclear Information System (INIS)

2009-04-01

This annual report issued by the Swiss Federal Nuclear Inspectorate (ENSI) reports on the work carried out by the Inspectorate in 2008. This report reviews the regulatory activities in the four Swiss nuclear power stations and in four further nuclear installations in various Swiss research facilities. It deals with topics such as operational details, technologies in use, radiation protection, radioactive wastes, emergency dispositions, personnel and provides an assessment of operations from the safety point of view. Also, the transportation of nuclear materials - both nuclear fuels and nuclear wastes - is reported on. General topics discussed include probabilistic safety analyses and accident management, earthquake damage analysis and agreements on nuclear safety. The underground disposal of highly-radioactive nuclear wastes and work done in the rock laboratories are discussed, as are proposals for additional nuclear power stations

Level of Evidence Associated with FDA Safety Communications with Drug Labeling Changes: 2010-2014

Directory of Open Access Journals (Sweden)

Benjamin Hixon

2017-02-01

Full Text Available Purpose: Approximately 800,000 safety reports are submitted to the FDA annually, however, only significant issues generate drug safety communications (DSC. The purpose of this study was to determine the type of clinical evidence used to warrant a change in drug labeling for drugs with DSC between January 1, 2010 and December 31, 2014. Methods: Selected data was obtained from the FDA website. The primary endpoint of the study was the frequency of the types of clinical evidence used in FDA communications, as reported through the FDA DSC. Results were evaluated via descriptive statistics, and chi-squared for nominal data. Results: A total of 2521 drug safety labeling changes were identified and 99 (3.9% of safety communications met the inclusion criteria. The majority of the labeling changes were associated with single agents (83.8%. The three most frequently reported labeling changes were warnings (68.7%, precautions (58.6%, and patient package insert/medication guide (23.2%. Case reports resulted in the greatest number of documented literature types (n = 791, followed by randomized controlled trials (n = 76, and case control/cohort studies (n = 74. Significantly more evidence for DSCs were classified as Level of Evidence B (LOE B, 68.6%, compared to LOE A (17.1%, and LOE C (14.1% (p = 0.007. Conclusions: The majority of drug labeling change initiators was associated with LOE equivalent to B. Practitioners should evaluate data associated with labeling changes to determine how to interpret the information for their patients. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Original Research

The Influence of Safety, Efficacy, and Medical Condition Severity on Natural versus Synthetic Drug Preference.

Science.gov (United States)

Meier, Brian P; Lappas, Courtney M

2016-11-01

Research indicates that there is a preference for natural v. synthetic products, but the influence of this preference on drug choice in the medical domain is largely unknown. We present 5 studies in which participants were asked to consider a hypothetical situation in which they had a medical issue requiring pharmacological therapy. Participants ( N = 1223) were asked to select a natural, plant-derived, or synthetic drug. In studies 1a and 1b, approximately 79% of participants selected the natural v. synthetic drug, even though the safety and efficacy of the drugs were identical. Furthermore, participants rated the natural drug as safer than the synthetic drug, and as that difference increased, the odds of choosing the natural over synthetic drug increased. In studies 2 and 3, approximately 20% of participants selected the natural drug even when they were informed that it was less safe (study 2) or less effective (study 3) than the synthetic drug. Finally, in study 4, approximately 65% of participants chose a natural over synthetic drug regardless of the severity of a specific medical condition (mild v. severe hypertension), and this choice was predicted by perceived safety and efficacy differences. Overall, these data indicate that there is a bias for natural over synthetic drugs. This bias could have implications for drug choice and usage. © The Author(s) 2015.

The impact of assay technology as applied to safety assessment in reducing compound attrition in drug discovery.

Science.gov (United States)

Thomas, Craig E; Will, Yvonne

2012-02-01

Attrition in the drug industry due to safety findings remains high and requires a shift in the current safety testing paradigm. Many companies are now positioning safety assessment at each stage of the drug development process, including discovery, where an early perspective on potential safety issues is sought, often at chemical scaffold level, using a variety of emerging technologies. Given the lengthy development time frames of drugs in the pharmaceutical industry, the authors believe that the impact of new technologies on attrition is best measured as a function of the quality and timeliness of candidate compounds entering development. The authors provide an overview of in silico and in vitro models, as well as more complex approaches such as 'omics,' and where they are best positioned within the drug discovery process. It is important to take away that not all technologies should be applied to all projects. Technologies vary widely in their validation state, throughput and cost. A thoughtful combination of validated and emerging technologies is crucial in identifying the most promising candidates to move to proof-of-concept testing in humans. In spite of the challenges inherent in applying new technologies to drug discovery, the successes and recognition that we cannot continue to rely on safety assessment practices used for decades have led to rather dramatic strategy shifts and fostered partnerships across government agencies and industry. We are optimistic that these efforts will ultimately benefit patients by delivering effective and safe medications in a timely fashion.

Adverse events reported to the Food and Drug Administration from 2004 to 2016 for cosmetics and personal care products marketed to newborns and infants.

Science.gov (United States)

Cornell, Erika; Kwa, Michael; Paller, Amy S; Xu, Shuai

2018-03-01

Despite their ubiquitous use and several recent health controversies involving cosmetics and personal care products for children, the Food and Drug Administration has little oversight of these products and relies on consumer-submitted adverse event reports. We assessed the recently released Center for Food Safety and Applied Nutrition's Adverse Event Reporting System database for adverse event reports submitted to the Food and Drug Administration for baby personal care products and to determine whether useful insights can be derived. We extracted the Center for Food Safety and Applied Nutrition's Adverse Event Reporting System data file from 2004 to 2016 and examined the subset classified according to the Food and Drug Administration-designated product class as a baby product. Events were manually categorized into product type and symptom type to assess for trends. Only 166 total adverse events were reported to the Food and Drug Administration for baby products from 2004 to 2016. The majority of reports indicated rash or other skin reaction; 46% of reported events led to a health care visit. Pediatric dermatologists should consider submitting cosmetics and personal care product adverse event reports and encouraging consumers to do so likewise in situations in which a product adversely affects a child's health. © 2018 Wiley Periodicals, Inc.

Risk Management: Earning Recognition with an Automated Safety Program

Science.gov (United States)

Lansberry, Linden; Strasburger, Tom

2012-01-01

Risk management is a huge task that requires diligent oversight to avoid penalties, fines, or lawsuits. Add in the burden of limited resources that schools face today, and the challenge of meeting the required training, reporting, compliance, and other administrative issues associated with a safety program is almost insurmountable. Despite an…

Oil and gas site contamination risks : improved oversight needed

International Nuclear Information System (INIS)

2010-02-01

British Columbia has seen record levels of activities in the oil and gas sector. Upstream petroleum processes include exploration, well completion and production. Site contamination can occur during all of these activities, resulting in potential environmental and human health impacts. Although well operators are responsible by law for site restoration, there is a potential risk that some operators will not fulfill their responsibilities, thereby leaving the province liable for the site restoration costs. In British Columbia, the BC Oil and Gas Commission (OGC) is responsible for managing these risks through oversight activities designed to ensure that industry meets its obligations. The OGC also manages the orphan sites reclamation fund. This report presented an audit of the OGC in order to determine if it is providing adequate oversight of upstream oil and gas site contamination risks. The audit examined whether the agency responsibilities are clear and whether the OGC is fully aware of the environmental and financial risks associated with upstream oil and gas site contamination. The audit also examined if the OGC has established appropriate procedures to oversee the risks and to inform the public of how effectively site contamination risks are being managed. The report presented the audit background, audit expectations, findings, conclusions and recommendations. It was concluded that the OGC's oversight of the environmental and financial risks associated with oil and gas site contamination needs improving. tabs., figs.

The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety.

Science.gov (United States)

Heal, D J; Cheetham, S C; Smith, S L

2009-12-01

Results from in vivo techniques, especially intracerebral microdialysis in freely-moving rats, have provided insights into potential mechanisms responsible for the efficacy and safety of catecholaminergic drugs for ADHD treatment. The drugs reviewed come from distinct pharmacological classes: psychostimulant releasing agents, eg d-amphetamine; psychostimulant reuptake inhibitors, eg dl-threo-methylphenidate (dl-MPH), and non-stimulant reuptake inhibitors, eg atomoxetine. Psychostimulants, which currently deliver the best efficacy in treating ADHD, exhibit the following characteristics on extraneuronal catecholamine concentrations in rodent brain in vivo: 1) They enhance the efflux and function of both noradrenaline and dopamine in the central nervous system. 2) The increase of dopamine efflux that they produce is not limited to cortical regions. 3) They have a rapid onset of action with no ceiling on drug effect. d-Amphetamine has a mechanism independent of neuronal firing rate, displacing intraneuronal stores of catecholamines, delaying their reuptake and inhibiting catabolism by monoamine oxidase. dl-MPH has an enigmatic, extraneuronal action that is neuronal firing rate-dependent and reuptake transporter-mediated, yet paradoxically, almost as powerful as that of d-amphetamine. In safety terms, these powerful catecholaminergic effects also make the psychostimulants liable for abuse. Since efficacy and safety derive from the same pharmacological mechanisms, it has not yet been possible to separate these two components. However, the development of once-daily psychostimulant formulations and a prodrug, lisdexamfetamine, has improved patient compliance and markedly reduced scope for their diversion/abuse. This review will discuss the in vivo pharmacological profiles of approved catecholaminergic drugs for treatment of ADHD and implications for their clinical efficacy and abuse liability.

Integrating GIS and GPS in environmental remediation oversight

International Nuclear Information System (INIS)

Kaletsky, K.; Earle, J.R.; Schneider, T.A.

1996-01-01

This paper presents findings on Ohio EPA Office of Federal Facilities Oversight's (OFFO) use of GIS and GPS for environmental remediation oversight at the U.S. Department of Energy's (DOE) Fernald Site. The Fernald site is a former uranium metal production facility within DOE's nuclear weapons complex. Significant uranium contamination of soil and groundwater is being remediated under state and federal regulations. OFFO uses GIS/GPS to enhance environmental monitoring and remediation oversight. These technologies are utilized within OFFO's environmental monitoring program for sample location and parameter selection, data interpretation and presentation. GPS is used to integrate sample data into OFFO's GIS and for permanently linking precise and accurate geographic data to samples and waste units. It is important to identify contamination geographically as all visual references (e.g., buildings, infrastructure) will be removed during remediation. Availability of the GIS allows OFFO to perform independent analysis and review of DOE contractor generated data, models, maps, and designs. This ability helps alleviate concerns associated with open-quotes black boxclose quotes models and data interpretation. OFFO's independent analysis has increased regulatory confidence and the efficiency of design reviews. GIS/GPS technology allows OFFO to record and present complex data in a visual format aiding in stakeholder education and awareness. Presented are OFFO's achievements within the aforementioned activities and some reasons learned in implementing the GIS/GPS program. OFFO's two years of GIS/GPS development have resulted in numerous lessons learned and ideas for increasing effectiveness through the use of GIS/GPS

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

International Nuclear Information System (INIS)

Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

2015-01-01

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

Energy Technology Data Exchange (ETDEWEB)

Wang, Kejian, E-mail: kejian.wang.bio@gmail.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Weng, Zuquan [Japan National Institute of Occupational Safety and Health, Kawasaki (Japan); Sun, Liya [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Sun, Jiazhi; Zhou, Shu-Feng [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States); He, Lin, E-mail: helin@Bio-X.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China)

2015-02-13

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.

Defense Forensics: Additional Planning and Oversight Needed to Establish an Enduring Expeditionary Forensic Capability

Science.gov (United States)

2013-06-01

forensic pathology, forensic anthropology, and forensic toxicology . 13DOD’s forensic directive defines DOD components as the Office of the...DEFENSE FORENSICS Additional Planning and Oversight Needed to Establish an Enduring Expeditionary Forensic ...COVERED 00-00-2013 to 00-00-2013 4. TITLE AND SUBTITLE Defense Forensics : Additional Planning and Oversight Needed to Establish an Enduring

Access to Investigational Drugs: FDA Expanded Access Programs or "Right-to-Try" Legislation?

Science.gov (United States)

Holbein, M E Blair; Berglund, Jelena P; Weatherwax, Kevin; Gerber, David E; Adamo, Joan E

2015-10-01

The Food and Drug Administration Expanded Access (EA) program and "Right-to-Try" legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access. FDA EA programs and state and federal legislative efforts to provide investigational products to patients by circumventing FDA regulations were summarized and compared. The FDA EA program includes Single Patient-Investigational New Drug (SP-IND), Emergency SP-IND, Intermediate Sized Population IND, and Treatment IND. Approval rates for all categories exceed 99%. Approval requires FDA and Institutional Review Board (IRB) approval, and cooperation of the pharmaceutical partner is essential. "Right-to-Try" legislation bypasses some of these steps, but provides no regulatory or safety oversight. The FDA EA program is a reasonable option for patients for whom all other therapeutic interventions have failed. The SP-IND not only provides patient access to new drugs, but also maintains a balance between immediacy and necessary patient protection. Rather than circumventing existing FDA regulations through proposed legislation, it seems more judicious to provide the knowledge and means to meet the EA requirements. © 2015 Wiley Periodicals, Inc.

Krsko NPP Periodic Safety Review program

International Nuclear Information System (INIS)

Basic, I.; Spiler, J.; Novsak, M.

2001-01-01

The need for conducting a Periodic Safety Review for the Krsko NPP has been clearly recognized both by the NEK and the regulator (SNSA). The PSR would be highly desirable both in the light of current trends in safety oversight practices and because of many benefits it is capable to provide. On January 11, 2001 the SNSA issued a decision requesting the Krsko NPP to prepare a program and determine a schedule for the implementation of the program for 'Periodic Safety Review of NPP Krsko'. The program, which is required to be in accordance with the IAEA safety philosophy and with the EU practice, was submitted for the approval to the SNSA by the end of March 2001. The paper summarizes Krsko NPP Periodic Safety Review Program [1] including implemented SNSA and IAEA Expert Mission comments.(author)

Tennessee Oversight Agreement annual report, May 13, 1993 - May 12, 1994

International Nuclear Information System (INIS)

1994-01-01

This report discusses the activities of the Division of DOE Oversight in the areas of coordination with other State Agencies with regard to environmental restoration, corrective action, and waste management activities on the Oak Ridge Reservation; and the Division's efforts to keep the public informed of those DOE activities that may impact their health and the environment. This report includes the status of the Division's efforts in implementing the Tennessee Oversight Agreement (TOA). Each Program Section provides information concerning the status of its activities. The Administrative Section has been instrumental in achieving access to the ORR without prior notification to DOE and in obtaining documents and environmental, waste management, safety, and health information in a timely manner. The Environmental Restoration Program has provided in-depth document reviews and on-site coordination and monitoring of field activities required under the Federal Facility Agreement. Most notable of the activities are the investigations and planned remediation of the Lower East Fork Poplar Creek and the Watts Bar Reservoir. The Waste Management Program has audited DOE's compliance with air, water, solid, hazardous, and mixed waste storage, treatment, and disposal regulations. Effort was focused on all three DOE Facilities on the ORR. The final portion of this report discusses the Division's findings and recommendations. Most significant of these issues is the Division's request to be an active participant in DOE's prioritization of its TOA commitments. Other issues discussed include long term storage of radioactive waste and the use of environmental restoration funds. A discussion of those findings and recommendations provided in last year's annual report and addressed by DOE are included in this report as well. All documents, logs, files, etc. supporting this report are available for review during routine business hours at the Division's office

Advancing pharmaceuticals and patient safety in Saudi Arabia: A 2030 vision initiative

Directory of Open Access Journals (Sweden)

Tariq M. Alhawassi

2018-01-01

Full Text Available Low-quality medicines deliver sub-optimal clinical outcomes and waste precious health resources. It is important to ensure that public funds are spent on healthcare technologies that meet national regulatory bodies such as the Saudi Food and Drug Authority (SFDA, quality standards for safety, efficacy, and quality. Medicines quality is a complicated combination of pre-market regulatory specifications, appropriate sourcing of ingredients (active pharmaceutical ingredient (API, excipients, etc., manufacturing processes, healthcare ecosystem communications, and regular and robust pharmacovigilance practices. A recent conference in Riyadh, sponsored by King Saud University, sought to discuss these issues and develop specific policy recommendations for the Saudi 2030 Vision plan. This and other efforts will require more and more creative educational programs for physicians, pharmacists, hospitals, and patients, and, most importantly evolving regulations on quality standards and oversight by Saudi health authorities.

Safety Profile of the Newest Antiepileptic Drugs: A Curated Literature Review.

Science.gov (United States)

Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista

2017-01-01

Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

DEFF Research Database (Denmark)

Dybdahl, Torben; Andersen, Morten; Søndergaard, Jens

2004-01-01

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

How do pharmaceutical companies handle consumer adverse drug reaction reports? An overview based on a survey of French drug safety managers and officers.

Science.gov (United States)

Fleuranceau-Morel, P

2002-01-01

It is surprising to see how consumer Adverse Drug Reaction (ADR) reports have been continuously increasing for the last few years in Europe. This probably results from the influence of United States (US) market where the patients feels justified in telephoning the pharmaceutical companies directly with queries regarding their treatment. The growing number of alternative sources of information (e.g. health and popular magazines, spots on radio and TV etc.) to which a consumer is exposed has added to this growth too. The changing relationship between patients and doctors may also contribute to this phenomenon. It is then interesting to evaluate the way pharmaceutical companies currently deal with consumer ADR reports. The management of consumer ADR reporting was investigated by means of a questionnaire sent to 46 French drug safety managers and drug safety officers (DSOs) of multinational pharmaceutical companies. The analysis of the survey stressed the fact that pharmaceutical companies should be prepared to face up to an increase in the number of consumer ADR reports. It clearly appears that the consumers who telephone to register side-effects should be forwarded to a trained DSO with medical or pharmaceutical background and the communication skills acquired through specific training. This person should also be able to release adequate product information validated by his/her own company. The influence of the US market seems to be changing the way pharmaceutical companies deal with consumer ADR reports. Nowadays, these reports are entered into a drug safety database by most of the companies without previously having contacted the patient's general practitioner (GP) or specialist for medical confirmation. Lastly, the drug safety managers and DSOs consulted have divided opinions about the usefulness of call centres and e-mails as tools for ADR reporting. But both tools are globally rejected by the pharmaceutical companies as a reliable means of reporting. As stated

Drug Safety Monitoring in Children: Performance of Signal Detection Algorithms and Impact of Age Stratification

NARCIS (Netherlands)

O.U. Osokogu (Osemeke); C. Dodd (Caitlin); A.C. Pacurariu (Alexandra C.); F. Kaguelidou (Florentia); D.M. Weibel (Daniel); M.C.J.M. Sturkenboom (Miriam)

2016-01-01

textabstractIntroduction: Spontaneous reports of suspected adverse drug reactions (ADRs) can be analyzed to yield additional drug safety evidence for the pediatric population. Signal detection algorithms (SDAs) are required for these analyses; however, the performance of SDAs in the pediatric

From Drug Safety to Drug Security: A Contemporary Shift in the Policing of Health.

Science.gov (United States)

Hornberger, Julia

2018-01-29

The counterfeiting of medication is increasingly seen as a major threat to health, especially in the light of both the everyday reliance on and a broadening of world-wide access to pharmaceuticals. Exaggerated or real, this threat has inaugurated, this article argues, a shift from a drug safety regime to a drug security regime that governs the flow of pharmaceuticals and brings together markets, police, and health actors in new ways. This entails a shift from soft disciplinary means aimed at incremental and continued inclusion of defaulters, to one of drastically sovereign measures of exclusion and banishment aimed at fake goods and the people associated with them, in the name of health. Through a multi-sited ethnographic study, this article shows how such new drug security efforts play themselves out especially in (South) Africa, highlighting a modus operandi of spectacular performativity and of working through suspicion and association rather than factuality, producing value less so for those in need of health than for a petty security industry itself. © 2018 by the American Anthropological Association.

15 CFR 2008.18 - Information Security Oversight Committee.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Information Security Oversight Committee. 2008.18 Section 2008.18 Commerce and Foreign Trade Regulations Relating to Foreign Trade Agreements OFFICE OF THE UNITED STATES TRADE REPRESENTATIVE REGULATIONS TO IMPLEMENT E.O. 12065; OFFICE OF...

Safety of Etoricoxib, Celecoxib, and Nonselective Nonsteroidal Antiinflammatory Drugs in Ankylosing Spondylitis and Other Spondyloarthritis Patients

DEFF Research Database (Denmark)

Kristensen, L E; Jakobsen, A K; Askling, J

2015-01-01

OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardio......OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular...

Online availability and safety of drugs in shortage: a descriptive study of internet vendor characteristics.

Science.gov (United States)

Liang, Bryan A; Mackey, Tim K

2012-02-09

Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. We performed a descriptive study of the prevalence of online marketing for shortage drugs-that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing.

Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy

Directory of Open Access Journals (Sweden)

Jinsoo Lee

2016-01-01

Full Text Available Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p=0.0284, Fisher’s exact test. Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children.

Safety of diabetes drugs in patients with heart failure.

Science.gov (United States)

Carrasco-Sánchez, F J; Ostos-Ruiz, A I; Soto-Martín, M

2018-03-01

Heart failure (HF) and diabetes mellitus are 2 clinical conditions that often coexist, particularly in patients older than 65 years. Diabetes mellitus promotes the development of HF and confers a poorer prognosis. Hypoglycaemic agents (either by their mechanism of action, hypoglycaemic action or adverse effects) can be potentially dangerous for patients with HF. In this study, we performed a review of the available evidence on the safety of diabetes drugs in HF, focused on the main observational and experimental studies. Recent studies on cardiovascular safety have evaluated, although as a secondary objective, the impact of new hypoglycaemic agents on HF, helping us understand the neutrality, risks and potential benefits of these agents. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Adverse weather impact on aviation safety, investigation and oversight

Science.gov (United States)

Smith, M. J.

1985-01-01

A brief review of the weather factors that effect aviation safety with respect to U.S. Coast Guard operations is presented. Precise meteorological information is an absolute necessity to the Coast Guard which must conduct life saving and rescue operations under the worst of weather conditions. Many times the weather conditions in which they operate are the cause of or a contributing factor to the predicament from which they must execute a rescue operation.

Online Availability and Safety of Drugs in Shortage: A Descriptive Study of Internet Vendor Characteristics

Science.gov (United States)

Mackey, Tim K

2012-01-01

Background Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. Objective To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. Methods We performed a descriptive study of the prevalence of online marketing for shortage drugs—that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. Results Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. Conclusions FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing. PMID:22321731

Notification: Oversight of Clean Water State Revolving Loan Funds

Science.gov (United States)

Project #OA-FY15-0153, April 6, 2015. The Office of Inspector General (OIG) for the U.S. Environmental Protection Agency (EPA) is beginning preliminary research on the EPA oversight of the Clean Water State Revolving Fund (CWSRF).

Access to Investigational Drugs: FDA Expanded Access Programs or “Right‐to‐Try” Legislation?

Science.gov (United States)

Berglund, Jelena P.; Weatherwax, Kevin; Gerber, David E.; Adamo, Joan E.

2015-01-01

Abstract Purpose The Food and Drug Administration Expanded Access (EA) program and “Right‐to‐Try” legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access. Methods FDA EA programs and state and federal legislative efforts to provide investigational products to patients by circumventing FDA regulations were summarized and compared. Results The FDA EA program includes Single Patient‐Investigational New Drug (SP‐IND), Emergency SP‐IND, Intermediate Sized Population IND, and Treatment IND. Approval rates for all categories exceed 99%. Approval requires FDA and Institutional Review Board (IRB) approval, and cooperation of the pharmaceutical partner is essential. “Right‐to‐Try” legislation bypasses some of these steps, but provides no regulatory or safety oversight. Conclusion The FDA EA program is a reasonable option for patients for whom all other therapeutic interventions have failed. The SP‐IND not only provides patient access to new drugs, but also maintains a balance between immediacy and necessary patient protection. Rather than circumventing existing FDA regulations through proposed legislation, it seems more judicious to provide the knowledge and means to meet the EA requirements. PMID:25588691

Nuclear health and safety. Status of GAO's environmental, safety, and health recommendations to DOE

International Nuclear Information System (INIS)

England-Joseph, Judy; Bannerman, Carl J.; Fenzel, William F.; Brack, David L.; Harter, Frederick A.

1990-04-01

DOE's operations are carried out at many contractor-operated sites around the country, including major sites within the nuclear weapons complex that are involved in the production of nuclear material for weapons and naval fuel. At these sites DOE contractors routinely use and generate large quantities of a wide range of hazardous and radioactive materials. Because these materials require special handling by workers. Also pursuant to Mar. 15, 1989, request, we provided you a report entitled Nuclear Health and Safety: Need for Improved Responsiveness to Problems at DOE Sites (GAO/RCED-90-101, Mar. 28, 1990). to prevent exposure to themselves or releases into the environment, DOE's weapons complex, considered in its entirety, is among the potentially more dangerous industrial operations in the world. Over the last decade, at the request of the Congress, we have carried out a series of assessments and evaluations of various aspects of the complex. In over 60 reports and testimonies published since 1990, we have called attention to the mounting problems facing DOE's nuclear weapons complex. This body of work includes (1) identifying serious, costly, and widespread environmental, safety, and health problems at DOE facilities, (2) calling for outside independent oversight of DOE's nuclear operations, and (3) making recommendations to DOE to strengthen its oversight, providing more detailed information and plans to the Congress, and improving its management and accounting practices. In total, our reports and testimonies have included 54 recommendations to DOE, in addition to recommendations to the Congress, concerning environmental, safety, and health matters at the complex. We consider 23 of the 54 recommendations to be still open. The open recommendations call for improvements such as tighter program controls and clearer standards and policies related to environmental, safety, and health matters

Identifying Adverse Drug Events by Relational Learning.

Science.gov (United States)

Page, David; Costa, Vítor Santos; Natarajan, Sriraam; Barnard, Aubrey; Peissig, Peggy; Caldwell, Michael

2012-07-01

The pharmaceutical industry, consumer protection groups, users of medications and government oversight agencies are all strongly interested in identifying adverse reactions to drugs. While a clinical trial of a drug may use only a thousand patients, once a drug is released on the market it may be taken by millions of patients. As a result, in many cases adverse drug events (ADEs) are observed in the broader population that were not identified during clinical trials. Therefore, there is a need for continued, post-marketing surveillance of drugs to identify previously-unanticipated ADEs. This paper casts this problem as a reverse machine learning task , related to relational subgroup discovery and provides an initial evaluation of this approach based on experiments with an actual EMR/EHR and known adverse drug events.

Anti-Obesity Drugs: A Review about Their Effects and Safety

Directory of Open Access Journals (Sweden)

Jun Goo Kang

2012-02-01

Full Text Available The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake. When the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In past years, numerous drugs have been approved for the treatment of obesity; however, most of them have been withdrawn from the market because of their adverse effects. In fact, amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an increased risk of psychiatric disorders and non-fatal myocardial infarction or stroke. Even if orlistat is not as effective as other drugs in reducing body weight, orlistat is presently the only available choice for the treatment of obesity because of its safety for cardiovascular events and positive effects on diabetic control. Hopefully, more effective and better tolerated anti-obesity drugs will be developed through an improved understanding of the multiple mechanisms and complex physiological systems targeting appetite.

Use of nonsteroidal anti-inflammatory drugs among healthy people and specific cerebrovascular safety

DEFF Research Database (Denmark)

Fosbøl, Emil L; Olsen, Anne-Marie Schjerning; Olesen, Jonas Bjerring

2014-01-01

BACKGROUND: Nonsteroidal anti-inflammatory drugs can increase bleeding and thrombosis, but little is known about the cerebrovascular safety of these drugs, especially among healthy people. AIMS: The aim of this study was to examine the risk of ischemic and hemorrhagic stroke associated with the use...... stroke). RESULTS: We selected 1,028,437 healthy individuals (median age 39 years). At least one nonsteroidal anti-inflammatory drug was claimed by 44·7% of the study population, and the drugs were generally used for a short period of time and in low doses. High-dose ibuprofen and diclofenac were......·35-3·42)]. CONCLUSIONS: In healthy individuals, use of commonly available nonsteroidal anti-inflammatory drugs such as ibuprofen, diclofenac, and naproxen was associated with increased risk of stroke....

76 FR 52997 - Public Company Accounting Oversight Board; Order Approving Proposed Board Funding Final Rules for...

Science.gov (United States)

2011-08-24

... Accounting Oversight Board; Order Approving Proposed Board Funding Final Rules for Allocation of the Board's... August 18, 2011. I. Introduction On June 21, 2011, the Public Company Accounting Oversight Board (the... public accounting firm, in amounts that are sufficient to cover the costs of processing and reviewing...

75 FR 36427 - Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management...

Science.gov (United States)

2010-06-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice...

Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

OpenAIRE

Castleden, C M; Pickles, H

1988-01-01

1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age grou...

76 FR 20686 - Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug...

Science.gov (United States)

2011-04-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0164] Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug, and Cosmetic Act; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

The role of the Australian Adverse Drug Reactions Advisory Committee (ADRAC) in monitoring drug safety

International Nuclear Information System (INIS)

Boyd, Ian W.

2002-01-01

The Australian adverse drug reaction reporting system is acknowledged as one of the best in the world. Despite its small population of less than 20 million people, Australia's current ADR reporting rate of over 12000 reports per year places it in the top few nations in terms of reports per capita. The ADRAC program has been in operation for over 30 years. Australia was a founding member of the WHO International Drug Monitoring Programme which commenced in 1968 and currently there are about 153000 reports in the ADRAC database. Reports from health professionals have uncovered a number of significant safety problems over the years. Of particular importance are flucloxacillin-induced hepatitis, amoxycillin/clavulanate-induced hepatitis, and the association of cystitis with tiaprofenic acid. The number and quality of the reports has allowed an understanding of the characteristics of the reactions and, using ADRAC reporters as a major source of cases, case-control studies have been completed which have identified risk factors. ADRAC's review of Australian reports has highlighted many important associations that have been disseminated through the Australian Adverse Drug Reactions Bulletin

The role of Quality Oversight in nuclear and hazardous waste management and environmental restoration at Westinghouse Hanford Company

International Nuclear Information System (INIS)

Fouad, H.Y.

1994-05-01

The historical factors that led to the waste at Hanford are outlined. Westinghouse Hanford Company mission and organization are described. The role of the Quality Oversight organization in nuclear hazardous waste management and environmental restoration at Westinghouse Hanford Company is delineated. Tank Waste Remediation Systems activities and the role of the Quality Oversight organization are described as they apply to typical projects. Quality Oversight's role as the foundation for implementation of systems engineering and operation research principles is pointed out

40 CFR 51.362 - Motorist compliance enforcement program oversight.

Science.gov (United States)

2010-07-01

... deviate from established requirements, or in the case of non-government entities that process... registrations; and (10) The prevention of fraudulent procurement or use of inspection documents by controlling... measurements. (c) SIP requirements. The SIP shall include a description of enforcement program oversight and...

What can nanosafety learn from drug development? The feasibility of “safety by design”

DEFF Research Database (Denmark)

Hjorth, Rune; van Hove, Lilian; Wickson, Fern

2017-01-01

“Safety by design” (SbD) is an intuitively appealing concept that is on the rise within nanotoxicology and nanosafety research, as well as within nanotechnology research policy. It leans on principles established within drug discovery and development (DDD) and seeks to address safety early, as well...... as throughout product development. However, it remains unclear what the concept of SbD exactly entails for engineered nanomaterials (ENMs) or how it is envisioned to be implemented. Here, we review the concept as it is emerging in European research and compare its resemblance with the safety testing...

[Investigation of the cognition and behavior on drug safety in Beijing middle school students].

Science.gov (United States)

Cheng, Y C; Pan, Y P; Zhang, Y; Pan, Y T; Ding, C Y; Cao, Y; Zhuo, L; Fang, R F; Gao, A Y; Guo, J; Li, A J; Fu, Q; Ma, J; Zhan, S Y

2017-12-18

To understand the cognition and behavior of drug safety in Beijing middle school students and provide advice for relevant education. A cross-sectional survey using paper questionnaires was carried out on the student body of nine Beijing middle schools. Multi-stage proportionate stratified cluster sampling was adopted to enroll participants. In addition to demographic questions, the questionnaire included 17 questions assessing the cognition and behavior of safe drug use, prioritizing questions that aligned with the health education guideline for primary and secondary school students from Chinese Ministry of Education. Descriptive statistical methods were applied using the SAS 9.2 software. Of the 4 220 students investigated, 2 097(49.7%) were males and 2 123(50.3%) were females. The average age was (14.3±1.7) years. 2 030(48.1%) students were from downtown areas, 1 511(35.8%) were from urban-rural linking areas and 679(16.1%) were from rural areas. Half (51.5%) of the respondents were junior high school students, and the others were from senior high schools (34.2%) and vocational high schools (14.3%). Most of the students (89.6%) lived off campus. The awareness rate of drug safety knowledge was 74.4%, the median score of drug safety behavior was 4 points (full score was 5 points) and there was a statistically positive correlation between the two (Spearman's correlation coefficient was 0.156, Pmiddle school students is good, but problems still exist in medication adherence, the management of expired drugs and the antibiotics cognition, which need to be fixed through specific, pointed way of education. And more efforts should be made to improve the cognition in rural regions, vocational high schools and on campus students.

Best practices: an electronic drug alert program to improve safety in an accountable care environment.

Science.gov (United States)

Griesbach, Sara; Lustig, Adam; Malsin, Luanne; Carley, Blake; Westrich, Kimberly D; Dubois, Robert W

2015-04-01

The accountable care organization (ACO), one of the most promising and talked about new models of care, focuses on improving communication and care transitions by tying potential shared savings to specific clinical and financial benchmarks. An important factor in meeting these benchmarks is an ACO's ability to manage medications in an environment where medical and pharmacy care has been integrated. The program described in this article highlights the critical components of Marshfield Clinic's Drug Safety Alert Program (DSAP), which focuses on prioritizing and communicating safety issues related to medications with the goal of reducing potential adverse drug events. Once the medication safety concern is identified, it is reviewed to evaluate whether an alert warrants sending prescribers a communication that identifies individual patients or a general communication to all physicians describing the safety concern. Instead of basing its decisions regarding clinician notification about drug alerts on subjective criteria, the Marshfield Clinic's DSAP uses an internally developed scoring system. The scoring system includes criteria developed from previous drug alerts, such as level of evidence, size of population affected, severity of adverse event identified or targeted, litigation risk, available alternatives, and potential for duration of medication use. Each of the 6 criteria is assigned a weight and is scored based upon the content and severity of the alert received.  In its first 12 months, the program targeted 6 medication safety concerns involving the following medications: topiramate, glyburide, simvastatin, citalopram, pioglitazone, and lovastatin. Baseline and follow-up prescribing data were gathered on the targeted medications. Follow-up review of prescribing data demonstrated that the DSAP provided quality up-to-date safety information that led to changes in drug therapy and to decreases in potential adverse drug events. In aggregate, nearly 10,000 total

Poor Government Oversight of Anham and Its Subcontracting Procedures Allowed Questionable Costs To Go Undetected

Science.gov (United States)

2011-07-30

contractor purchasing system review of Anham. Management Comments and Audit Response The Defense Contract Mangement Agency and the U.S. Central... Introduction 1  Background 1  Government Agency Roles and Oversight Responsibilities 4  Objectives 7  Weak Government Oversight Resulted in Significant...Subcontracting Procedures Allowed Questionable Costs To Go Undetected SIGIR 11-022 July 30, 2011 Introduction Since 2003, the United States Government

Safety culture in industrial radiography facility

International Nuclear Information System (INIS)

Vincent-Furo, Evelyn

2015-02-01

This project reviewed published IAEA materials and other documents on safety culture with specific references to industrial radiography. Safety culture requires all duties important to safety to be carried out correctly, with alertness, due thought and full knowledge, sound judgment and a proper sense of accountability. The development and maintenance of safety culture in an operating organization has to cover management systems, policies, responsibilities, procedures and organizational arrangements. The essence is to control radiation hazard, optimize radiation protection to prevent or reduce exposures and mitigate the consequences of accidents and incidents. To achieve a high degree of safety culture appropriate national and international infrastructure should exist to ensure effective training of workers and management system that supports commitment to safety culture at all level of the organization; management, managers and workforce. The result of the review revealed that all accidents in industrial radiography facilities were due to poor safety culture practices including inadequate regulatory control oversight. Some recommendations are provided and if implemented could improve safety culture leading to good safety performance which will significantly reduce accidents and their consequences in industrial radiography. These examples call for a review of safety culture in Industrial radiography. (au)

78 FR 52933 - Strengthening the Operating Framework and Furthering the Objectives of Coalition for Accelerating...

Science.gov (United States)

2013-08-27

... late-emerging issues. Standardized data will allow reviewers to increase review consistency and perform... functions and ongoing business operations, including premarket review, post-market safety, oversight of drug... trials, such as age and gender, have been established through Clinical Data Interchange Standards...

Insight and Lessons Learned on Organizational Factors and Safety Culture from the Review of Human Error-related Events of NPPs in Korea

International Nuclear Information System (INIS)

Kim, Ji Tae; Lee, Dhong Hoon; Choi, Young Sung

2014-01-01

Event investigation is one of the key means of enhancing nuclear safety deriving effective measures and preventing recurrences. However, it is difficult to analyze organizational factors and safety culture. This paper tries to review human error-related events from perspectives of organizational factors and safety culture, and to derive insights and lessons learned in developing the regulatory infrastructure of plant oversight on safety culture

Insight and Lessons Learned on Organizational Factors and Safety Culture from the Review of Human Error-related Events of NPPs in Korea

Energy Technology Data Exchange (ETDEWEB)

Kim, Ji Tae; Lee, Dhong Hoon; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2014-08-15

Event investigation is one of the key means of enhancing nuclear safety deriving effective measures and preventing recurrences. However, it is difficult to analyze organizational factors and safety culture. This paper tries to review human error-related events from perspectives of organizational factors and safety culture, and to derive insights and lessons learned in developing the regulatory infrastructure of plant oversight on safety culture.

78 FR 12369 - United States Government Policy for Institutional Oversight of Life Sciences Dual Use Research of...

Science.gov (United States)

2013-02-22

... Oversight of Life Sciences Dual Use Research of Concern AGENCY: Office of Science and Technology Policy... comments on the proposed United States Government Policy for Institutional Oversight of Life Sciences Dual... requirements for certain categories of life sciences research at institutions that accept Federal funding for...

Safety, efficacy, and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis

DEFF Research Database (Denmark)

Egeberg, A; Ottosen, M B; Gniadecki, R

2018-01-01

BACKGROUND: Real-life data on newer biologic and biosimilar agents for moderate-to-severe psoriasis are lacking. OBJECTIVES: To examine safety, efficacy, and time to discontinuation (drug survival) of biologics (adalimumab, etanercept, infliximab, secukinumab, and ustekinumab) and compare origina...... the long-term safety of novel biologics for psoriasis. This article is protected by copyright. All rights reserved....

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

Science.gov (United States)

Abraham, John; Davis, Courtney

2005-09-01

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

Regulatory oversight report 2007 concerning nuclear safety in Swiss nuclear installations

International Nuclear Information System (INIS)

2008-04-01

This annual report issued by the Swiss Federal Nuclear Inspectorate (HSK) reports on the work carried out by the Inspectorate in 2007. This report reviews the regulatory activities in the four Swiss nuclear power stations and in four further nuclear installations in various Swiss research facilities. It deals with topics such as operational details, technologies in use, radiation protection, radioactive wastes, emergency dispositions and personnel and provides an assessment of operations from the point of view of safety. Also, the transportation of nuclear materials - both nuclear fuels and nuclear wastes - is reported on. General topics discussed include probabilistic safety analyses and accident management. Finally, the disposal of nuclear wastes and work done in the rock laboratories in Switzerland is commented on

Drug safety alerts of pharmacovigilance programme of India: A scope for targeted spontaneous reporting in India

Directory of Open Access Journals (Sweden)

Prasad Thota

2018-01-01

Conclusion: In India, spontaneous reporting of ADRs existed since 1998 under passive surveillance method, but there is an urgent need to initiate TSR, which is a complementary method to spontaneous reporting on these drug safety alerts for further regulatory action by Central Drugs Standard Control Organization.

Transfer of safety responsibilities to future generations: regulatory tools

International Nuclear Information System (INIS)

Kotra, Janet P.

2008-01-01

In a forward-looking local development plan, Nye County defends a series of principles like safety, equity, and societal acceptability of responsibility (safety being foremost). The Nye County community clearly advocates permanent oversight of facilities. To respond to community requirements the regulators can establish requirements and guidance to ensure that safety obligations that can reasonably be discharged are in fact carried out and that remaining obligations are transferred as responsibly as possible, so that subsequent generations have the maximum flexibility to discharge their responsibility. There are transferred burdens of cost, risk and effort and these need to be at least partially compensated for by ensuring a subsequent transfer of information, resources and continuity of education, skills and research. The US regulatory requirements for disposal in a geological repository set out obligations in terms of land-ownership and control, records maintenance, performance confirmation, post-closure monitoring, monuments and markers, archives and records preservation and post-closure oversight. For the future the Nye County is proposing that there would be a co-ordinated involvement of the county in planning, development, operation and long term monitoring of the repository. They want to encourage the development of a live-work community for the repository workers so that they will be engaged in the local community as well as working at the facility

Preventing errors in administration of parenteral drugs: the results of a four-year national patient safety program.

NARCIS (Netherlands)

Blok, C. de; Schilp, J.; Wagner, C.

2013-01-01

Objectives: To evaluate the implementation of a four-year national patient safety program concerning the parenteral drug administration process in the Netherlands. Methods: Structuring the preparation and administration process of parenteral drugs reduces the number of medication errors. A

Mort User's Manual: For use with the Management Oversight and Risk Tree analytical logic diagram

Energy Technology Data Exchange (ETDEWEB)

Knox, N.W.; Eicher, R.W.

1992-02-01

This report contains the User's Manual for MORT (Management Oversight and Risk Tree), a logic diagram in the form of a work sheet'' that illustrates a long series of interrelated questions. MORT is a comprehensive analytical procedure that provides a disciplined method for determining the causes and contributing factors of major accidents. Alternatively, it serves as a tool to evaluate the quality of an existing system. While similar in many respects to fault tree analysis, MORT is more generalized and presents over 1500 specific elements of an ideal universal'' management program for optimizing environment, safety and health, and other programs. This User's Manual is intended to be used with the MORT diagram dated February 1992.

Sponsors’ and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials

Science.gov (United States)

Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

2017-01-01

Background/aims: The Food and Drug Administration’s final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. Methods: In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative–nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. Results: The investigative site’s responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors’“filtering” of

Sponsors' and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials.

Science.gov (United States)

Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

2017-06-01

The Food and Drug Administration's final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative-nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. The investigative site's responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors'"filtering" of reports and increased sponsor communication. Sponsors

Oversight of Department of Defense Reconstruction Projects in Afghanistan

Science.gov (United States)

2016-03-16

had to reschedule some of our site visits multiple times due to security conditions. As an alternative means for conducting oversight, due to a limited...employed less than 20 percent of the staff it was expected to employ. According to the doctors and nurses on site during our inspection, the limited

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety.

Science.gov (United States)

Roth, Sanford H

2011-01-01

Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.

The nuts and bolts of pills and portions: the functions of a drug safety working group.

Science.gov (United States)

Nath, Noleen S; Jones, Ellen H; Stride, Peter; Premaratne, Manuja; Thaker, Darshit; Lim, Ivan

2011-11-01

Hospitalised patients commonly experience adverse drug events (ADEs) and medication errors. Runciman reported that ADEs in hospitals account for 20% of reported adverse events and contribute to 27% of deaths where death followed an adverse event. Hughes recommends multidisciplinary hospital drug committees to assess performance and raise standards. The new Code of Conduct of the Medical Board of Australia recommends participation in systems for surveillance and monitoring of adverse events, and to improve patient safety. We describe the functions and role of a Drug Safety Working Group (DSWG) in a suburban hospital, which aims to audit and promote a culture of prescribing and medication administration that is prudent and cautious to minimise the risk of harm to patients. We believe that regular prescription monitoring and feedback to Resident Medical Officers (RMOs) improves medication management in our hospital.

The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

Science.gov (United States)

Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

2016-01-01

With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Plant safety and performance indicators for regulatory use

International Nuclear Information System (INIS)

Ferjancic, M.; Nemec, T.; Cimesa, S.

2004-01-01

Slovenian Nuclear Safety Administration (SNSA) supervises nuclear and radiological safety of Krsko NPP. This SNSA supervision is performed through inspections, safety evaluations of plant modifications and event analyses as well as with the safety and performance indicators (SPI) which are a valuable data source for plant safety monitoring. In the past SNSA relied on the SPI provided by Krsko NPP and did not have a set of SPI which would be more appropriate for regulatory use. In 2003 SNSA started with preparation of a new set of SPI which would be more suitable for performing the regulatory oversight of the plant. New internal SNSA procedure which is under preparation will define use and evaluation of SPI and will include definitions for the proposed set of SPI. According to the evaluation of SPI values in comparison with the limiting values and/or trending, the procedure will define SNSA response and actions. (author)

A Grey Area: Congressional Oversight of the Middle Ground Between Title 10 and Title 50

Science.gov (United States)

2012-06-01

1950’s, just a few short years after the Agency’s creation.1 With Watergate fresh on the country’s mind having just witnessed President Nixon’s...3 Congressional Oversight Legislative Overview Congressional oversight is not a result of modern scandals as one might think; it is as old as the...President Reagan’s tenure, however, members of Congress believed that he had overstepped his authority in the so-called “Iran-Contra affair.” The scandal

Regulatory oversight report 2012 concerning nuclear safety in Swiss nuclear installations

International Nuclear Information System (INIS)

2013-04-01

The Swiss Federal Nuclear Safety Inspectorate (ENSI) assesses and monitors nuclear facilities in Switzerland. These include the five nuclear power plants, the interim storage facilities based at each plant, the Central Interim Storage Facility (ZWILAG) and the nuclear facilities at the Paul Scherrer Institute (PSI), at the Federal Institute of Technology in Lausanne (EPFL) and at the University of Basel. Using a combination of inspections, regulatory meetings, examinations and analyses together with reports from the licensees of individual facilities, ENSI obtains the required overview of nuclear safety in the relevant facilities. It ensures that the facilities comply with the regulations and operate as required by law. Its regulatory responsibilities also include the transport of radioactive materials from and to nuclear facilities and the preparations for a deep geological repository for nuclear waste. ENSI maintains its own emergency organisation. It formulates and updates its own guidelines which stipulate the criteria for evaluating the current activities and future plans of the operators of nuclear facilities. ENSI produces regular reports on its regulatory activities and nuclear safety in Swiss nuclear facilities. It fulfils its statutory obligation to provide the public with information on particular events and findings in nuclear facilities. In 2012, the five nuclear power plants in Switzerland were all operated safely. 34 events were reported; on the international INES scale of 0 to 7, ENSI rated 33 events as Level 0 and 1 as Level 1. ENSI evaluates the safety of each nuclear power plant as part of a systematic safety evaluation taking account of both reportable events and other findings, in particular the results of more than 400 inspections conducted by ENSI during 2012. ZWILAG consists of several interim storage halls, a conditioning plant and an incineration/melting plant. At the end of 2012, the cask storage hall contained 40 transport/storage casks

Radiation Engineering and Safety Services by RSA TSO's View of Roles from a FBO/Non-Profit Healthcare Perspective

International Nuclear Information System (INIS)

Rugut, J.

2017-01-01

CHAK is a leading national Faith Based Organization (FBO) of Protestant churches' health facilities and programs from all over Kenya. Established in 1946 to promote access to quality health care. TSO’s are vetted, selected and licensed under the RPB Kenya act cap 243. Legal notice 160 of 2010 to Provides Radiology facilities’ designs, Construction Supervision to ensure adequate shielding. Kenya chose TSOs Sub contracting to complement Government’s efforts in promoting competence and identify inadequacies and oversights. Kenya chose TSOs Sub contracting to complement Government’s efforts in promoting competence and identify inadequacies and oversights. Safety Dose Limits Based on ICRP Publications and other Basic Safety Standards We Use In Kenya. Occupational doses;- 20 mSv/yr for radiation. The Public, and workers is 5 mSv/yr which is a times is a derivatives of other factors

MEDICAID FINANCIAL MANAGEMENT: Better Oversight of State Claims for Federal Reimbursement Needed

National Research Council Canada - National Science Library

Calbom, Linda

2002-01-01

.... Developing baseline information on Medicaid issues at greatest risk for improper payments and measuring improvements in program management against that baseline is key to achieving effective financial oversight...

76 FR 22944 - Pipeline Safety: Notice of Public Webinars on Implementation of Distribution Integrity Management...

Science.gov (United States)

2011-04-25

... oversight program and operating conditions as well as the evolutionary process that distribution system... 20590. Hand Delivery: Docket Management System, Room W12-140, on the ground floor of the West Building... PHMSA-2011-0084] Pipeline Safety: Notice of Public Webinars on Implementation of Distribution Integrity...

MO-AB-201-01: Regulatory Compliance and Safety with New Radiotherapies: Spheres and Ra-223

Energy Technology Data Exchange (ETDEWEB)

Phillips, L. [Stanford University (United States)

2015-06-15

The role of the Radiation Safety Officer at a medical facility can be complicated. The complexity of the position is based on the breadth of services provided at the institution and the nature of the radioactive materials license. Medical practices are constantly changing and the use of ionizing radiation continues to rise in this area. Some of the newer medical applications involving radiation have unique regulatory and safety issues that must be addressed. Oversight of the uses of radiation start at the local level (radiation safety officer, radiation safety committee) and are heavily impacted by outside agencies (i.e. Nuclear Regulatory Commission, State Radiologic Health, The Joint Commission (TJC), etc). This session will provide both an overview of regulatory oversight and essential compliance practices as well as practical ways to assess and introduce some of the new applications utilizing radioactive materials into your medical facility. Learning Objectives: Regulatory Compliance and Safety with New Radiotherapies: Spheres and Ra-223 (Lance Phillips) Understand the radioactive materials license amendment process to add new radiotherapies (i.e., SIR-Spheres, Therasphere, Xofigo). Understand the AU approval process for microspheres and Xofigo. Examine the training and handling requirements for new procedures. Understand the process involved with protocol development, SOP in order to define roles and responsibilities. The RSO and The RSC: Challenges and Opportunities (Colin Dimock) Understand how to form an effective Committee. Examine what the Committee does for the Program and the RSO. Understand the importance of Committee engagement. Discuss the balance of the complimentary roles of the RSO and the Committee. The Alphabet Soup of Regulatory Compliance: Being Prepared for Inspections (Linda Kroger) Recognize the various regulatory bodies and organizations with oversight or impact in Nuclear Medicine, Radiology and Radiation Oncology. Examine 10CFR35

MO-AB-201-01: Regulatory Compliance and Safety with New Radiotherapies: Spheres and Ra-223

International Nuclear Information System (INIS)

Phillips, L.

2015-01-01

The role of the Radiation Safety Officer at a medical facility can be complicated. The complexity of the position is based on the breadth of services provided at the institution and the nature of the radioactive materials license. Medical practices are constantly changing and the use of ionizing radiation continues to rise in this area. Some of the newer medical applications involving radiation have unique regulatory and safety issues that must be addressed. Oversight of the uses of radiation start at the local level (radiation safety officer, radiation safety committee) and are heavily impacted by outside agencies (i.e. Nuclear Regulatory Commission, State Radiologic Health, The Joint Commission (TJC), etc). This session will provide both an overview of regulatory oversight and essential compliance practices as well as practical ways to assess and introduce some of the new applications utilizing radioactive materials into your medical facility. Learning Objectives: Regulatory Compliance and Safety with New Radiotherapies: Spheres and Ra-223 (Lance Phillips) Understand the radioactive materials license amendment process to add new radiotherapies (i.e., SIR-Spheres, Therasphere, Xofigo). Understand the AU approval process for microspheres and Xofigo. Examine the training and handling requirements for new procedures. Understand the process involved with protocol development, SOP in order to define roles and responsibilities. The RSO and The RSC: Challenges and Opportunities (Colin Dimock) Understand how to form an effective Committee. Examine what the Committee does for the Program and the RSO. Understand the importance of Committee engagement. Discuss the balance of the complimentary roles of the RSO and the Committee. The Alphabet Soup of Regulatory Compliance: Being Prepared for Inspections (Linda Kroger) Recognize the various regulatory bodies and organizations with oversight or impact in Nuclear Medicine, Radiology and Radiation Oncology. Examine 10CFR35

Social Media Impact of the Food and Drug Administration's Drug Safety Communication Messaging About Zolpidem: Mixed-Methods Analysis.

Science.gov (United States)

Sinha, Michael S; Freifeld, Clark C; Brownstein, John S; Donneyong, Macarius M; Rausch, Paula; Lappin, Brian M; Zhou, Esther H; Dal Pan, Gerald J; Pawar, Ajinkya M; Hwang, Thomas J; Avorn, Jerry; Kesselheim, Aaron S

2018-01-05

The Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake. The objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem. We used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between -0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes "Related queries" during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website's editorial history, which lists all revisions to a given page and the editor's identity. In total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC; Google searches increased on the week of the

Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations from the Clinical Trials Transformation Initiative Investigational New Drug Safety Advancement Project.

Science.gov (United States)

Perez, Raymond P; Finnigan, Shanda; Patel, Krupa; Whitney, Shanell; Forrest, Annemarie

2016-12-15

Use of electronic clinical trial portals has increased in recent years to assist with sponsor-investigator communication, safety reporting, and clinical trial management. Electronic portals can help reduce time and costs associated with processing paperwork and add security measures; however, there is a lack of information on clinical trial investigative staff's perceived challenges and benefits of using portals. The Clinical Trials Transformation Initiative (CTTI) sought to (1) identify challenges to investigator receipt and management of investigational new drug (IND) safety reports at oncologic investigative sites and coordinating centers and (2) facilitate adoption of best practices for communicating and managing IND safety reports using electronic portals. CTTI, a public-private partnership to improve the conduct of clinical trials, distributed surveys and conducted interviews in an opinion-gathering effort to record investigator and research staff views on electronic portals in the context of the new safety reporting requirements described in the US Food and Drug Administration's final rule (Code of Federal Regulations Title 21 Section 312). The project focused on receipt, management, and review of safety reports as opposed to the reporting of adverse events. The top challenge investigators and staff identified in using individual sponsor portals was remembering several complex individual passwords to access each site. Also, certain tasks are time-consuming (eg, downloading reports) due to slow sites or difficulties associated with particular operating systems or software. To improve user experiences, respondents suggested that portals function independently of browsers and operating systems, have intuitive interfaces with easy navigation, and incorporate additional features that would allow users to filter, search, and batch safety reports. Results indicate that an ideal system for sharing expedited IND safety information is through a central portal used by

PARTICULARITIES OF PARLIAMENTARY OVERSIGHT IN DIFFERENT POLITICAL REGIMES

Directory of Open Access Journals (Sweden)

Silvia-Claudia CĂLIN-MIHALCEA

2015-07-01

Full Text Available The quality and intensity of the parliamentary oversight performed over the Government are shaped by several major criteria: political regime, electoral system, structure of the Parliament (unicameral/bicameral, parliamentary culture and tradition. This paper emphasizes some distinctive elements and particular mechanisms of the control exercised over the activities of the executive power, from the point of view of the political regime established in states with modern democracies.

Efficacy and safety of rabeprazole in non-steroidal anti-inflammatory drug-induced ulcer in Japan.

Science.gov (United States)

Mizokami, Yuji

2009-10-28

To investigate the efficacy and safety of rabeprazole under continuous non-steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer in Japan. Subjects comprised patients undergoing NSAID treatment in whom upper gastrointestinal endoscopy revealed an ulcerous lesion (open ulcer) with diameter > or = 3 mm, who required continuous NSAID treatment. Endoscopies were performed at the start of treatment, during the treatment period, and at the conclusion (or discontinuation) of treatment. Findings were evaluated as size (maximum diameter) and stage based on the Sakita-Miwa classification. An ulcer was regarded as cured when the "white coating" was seen to have disappeared under endoscopy. As criteria for evaluating safety, all medically untoward symptoms and signs (adverse events, laboratory abnormalities, accidental symptoms, etc.) occurring after the start of rabeprazole treatment were handled as adverse events. Endoscopic cure rate in 38 patients in the efficacy analysis (endoscopic evaluation) was 71.1% (27/38). Among those 38 patients, 35 had gastric ulcer with a cure rate of 71.4% (25/35), and 3 had duodenal ulcer with a cure rate of 66.7% (2/3). Three adverse drug reactions were reported from 64 patients in the safety analysis (interstitial pneumonia, low white blood cell count and pruritus); thus, the incidence rate for adverse drug reactions was 4.7% (3/64). The treatment efficacy of rabeprazole for NSAID-induced ulcer under continuous NSAID administration was confirmed.

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

Science.gov (United States)

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

2015-07-15

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

Safety assessment of Olkiluoto NPP units 1 and 2. Decision of the Radiation and Nuclear Safety Authority regarding the periodic safety review of the Olkiluoto NPP

International Nuclear Information System (INIS)

2010-02-01

In this safety assessment the Radiation and Nuclear Safety Authority (STUK) has evaluated the safety of the Olkiluoto Nuclear Power Plant units 1 and 2 in connection with the periodic safety review. This safety assessment provides a summary of the reviews, inspections and continuous oversight carried out by STUK. The issues addressed in the assessment and the related evaluation criteria are set forth in the nuclear energy and radiation safety legislation and the regulations issued thereunder. The provisions of the Nuclear Energy Act concerning the safe use of nuclear energy, security and emergency preparedness arrangements, and waste management are specified in more detail in the Government Decrees and Regulatory Guides issued by STUK. Based on the assessment, STUK consideres that the Olkiluoto Nuclear Power Plant units 1 and 2 meet the set safety requirements for operational nuclear power plants, the emergency preparedness arrangements are sufficient and the necessary control to prevent the proliferation of nuclear weapons has been appropriately arranged. The physical protection of the Olkiluoto nuclear power plant is not yet completely in compliance with the requirements of Government Decree 734/2008, which came into force in December 2008. Further requirements concerning this issue based also on the principle of continuous improvement were included in the decision relating to the periodic safety review. The safety of the Olkiluoto nuclear power plant was assessed in compliance with the Government Decree on the Safety of Nuclear Power Plants (733/2008), which came into force in 2008. The decree notes that existing nuclear power plants need not meet all the requirements set out for new plants. Most of the design bases pertaining to the Olkiluoto 1 and 2 nuclear power plant units were set in the 1970s. Substantial modernisations have been carried out at the Olkiluoto 1 and 2 nuclear power plant units since their commissioning to improve safety. This is in line with

Implementation of a patient safety program at a tertiary health system: A longitudinal analysis of interventions and serious safety events.

Science.gov (United States)

Cropper, Douglas P; Harb, Nidal H; Said, Patricia A; Lemke, Jon H; Shammas, Nicolas W

2018-04-01

We hypothesize that implementation of a safety program based on high reliability organization principles will reduce serious safety events (SSE). The safety program focused on 7 essential elements: (a) safety rounding, (b) safety oversight teams, (c) safety huddles, (d) safety coaches, (e) good catches/safety heroes, (f) safety education, and (g) red rule. An educational curriculum was implemented focusing on changing high-risk behaviors and implementing critical safety policies. All unusual occurrences were captured in the Midas system and investigated by risk specialists, the safety officer, and the chief medical officer. A multidepartmental committee evaluated these events, and a root cause analysis (RCA) was performed. Events were tabulated and serious safety event (SSE) recorded and plotted over time. Safety success stories (SSSs) were also evaluated over time. A steady drop in SSEs was seen over 9 years. Also a rise in SSSs was evident, reflecting on staff engagement in the program. The parallel change in SSEs, SSSs, and the implementation of various safety interventions highly suggest that the program was successful in achieving its goals. A safety program based on high-reliability organization principles and made a core value of the institution can have a significant positive impact on reducing SSEs. © 2018 American Society for Healthcare Risk Management of the American Hospital Association.

Challenges and strategies to facilitate formulation development of pediatric drug products: Safety qualification of excipients.

Science.gov (United States)

Buckley, Lorrene A; Salunke, Smita; Thompson, Karen; Baer, Gerri; Fegley, Darren; Turner, Mark A

2018-02-05

A public workshop entitled "Challenges and strategies to facilitate formulation development of pediatric drug products" focused on current status and gaps as well as recommendations for risk-based strategies to support the development of pediatric age-appropriate drug products. Representatives from industry, academia, and regulatory agencies discussed the issues within plenary, panel, and case-study breakout sessions. By enabling practical and meaningful discussion between scientists representing the diversity of involved disciplines (formulators, nonclinical scientists, clinicians, and regulators) and geographies (eg, US, EU), the Excipients Safety workshop session was successful in providing specific and key recommendations for defining paths forward. Leveraging orthogonal sources of data (eg. food industry, agro science), collaborative data sharing, and increased awareness of the existing sources such as the Safety and Toxicity of Excipients for Paediatrics (STEP) database will be important to address the gap in excipients knowledge needed for risk assessment. The importance of defining risk-based approaches to safety assessments for excipients vital to pediatric formulations was emphasized, as was the need for meaningful stakeholder (eg, patient, caregiver) engagement. Copyright © 2017 Elsevier B.V. All rights reserved.

49 CFR 659.25 - Annual review of system safety program plan and system security plan.

Science.gov (United States)

2010-10-01

... system security plan. 659.25 Section 659.25 Transportation Other Regulations Relating to Transportation... and system security plan. (a) The oversight agency shall require the rail transit agency to conduct an annual review of its system safety program plan and system security plan. (b) In the event the rail...

Drug Safety: Managing Multiple Drugs

Science.gov (United States)

... This series is produced by Consumers Union and Consumer Reports Best Buy Drugs , a public information project sup- ported by grants from the Engelberg Foundation and the National Library of Medicine of ... Consumer and Prescriber Education Grant Program which is funded ...

78 FR 59038 - Mobile Medical Applications; Guidance for Industry and Food and Drug Administration Staff...

Science.gov (United States)

2013-09-25

... FDA intends to apply its regulatory oversight to only those mobile apps that are medical devices and...] Mobile Medical Applications; Guidance for Industry and Food and Drug Administration Staff; Availability...) is announcing the availability of the guidance entitled ``Mobile Medical Applications.'' The FDA is...

48 CFR 36.609-3 - Work oversight in architect-engineer contracts.

Science.gov (United States)

2010-10-01

... architect-engineer contracts. 36.609-3 Section 36.609-3 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Architect-Engineer Services 36.609-3 Work oversight in architect-engineer contracts. The contracting officer...

MORT: a safety management program developed for ERDA

International Nuclear Information System (INIS)

1977-03-01

ERDA's System Safety Development Center (SSDC) is located at the Idaho National Engineering Laboratory under the EG and G Idaho, Inc., contract administered by the Idaho Operations Office. The SSDC performs a variety of tasks for ERDA's Division of Safety, Standards, and Compliance, for the purpose of improvement and application of safety program elements. Primary among these tasks are development and demonstration of new methodologies, training, consultation, and technical writing. This information package (ERDA 77-38) is an example of the later task, aimed at communicating to a general audience the nature and purpose of major features of the Management Oversight and Risk Tree (MORT) program. The SSDC also originates a guideline series of monographs (the ERDA 76-45 series) for individuals who desire more specific explanations of the MORT program

Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

Science.gov (United States)

Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

2016-02-01

Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The

Specialty pharmacies and other restricted drug distribution systems: financial and safety considerations for patients and health-system pharmacists.

Science.gov (United States)

Kirschenbaum, Bonnie E

2009-12-15

To discuss the role of restricted drug distribution systems in the implementation of risk evaluation and mitigation strategies (REMS), health-system pharmacists' concerns associated with the use of specialty pharmacies and other restricted drug distribution systems, reimbursement policies for high-cost specialty drugs, supply chain models for traditional and specialty drugs, and emerging trends in the management of and reimbursement for specialty pharmaceuticals. Restricted drug distribution systems established by pharmaceutical manufacturers, specialty pharmacies, or other specialty suppliers may be a component of REMS, which are required by the Food and Drug Administration for the management of known or potential serious risks from certain drugs. Concerns of health-system pharmacists using specialty suppliers include access to pharmaceuticals, operational challenges, product integrity, financial implications, continuity of care, and patient safety. An ambulatory care patient taking a specialty drug product from home to a hospital outpatient clinic or inpatient setting for administration, a practice known as "brown bagging," raises concerns about product integrity and institutional liability. An institution's finances, tolerance for liability, and ability to skillfully manage the processes involved often determine its choice between an approach that prohibits brown bagging but is costly and one that permits the practice under certain conditions and is less costly. The recent shift from a traditional supply chain model to a specialty pharmacy supply chain model for high-cost pharmaceuticals has the potential to increase pharmaceutical costs for health systems. A dialogue is needed between health-system pharmacists and group purchasing organizations to address the latter's role in mitigating the financial implications of this change and to help clarify the safety issues. Some health plans have shifted part of the cost of expensive drugs to patients by establishing a

Policy, Practice, and Research Agenda for Emergency Medical Services Oversight: A Systematic Review and Environmental Scan.

Science.gov (United States)

Taymour, Rekar K; Abir, Mahshid; Chamberlin, Margaret; Dunne, Robert B; Lowell, Mark; Wahl, Kathy; Scott, Jacqueline

2018-02-01

Introduction In a 2015 report, the Institute of Medicine (IOM; Washington, DC USA), now the National Academy of Medicine (NAM; Washington, DC USA), stated that the field of Emergency Medical Services (EMS) exhibits signs of fragmentation; an absence of system-wide coordination and planning; and a lack of federal, state, and local accountability. The NAM recommended clarifying what roles the federal government, state governments, and local communities play in the oversight and evaluation of EMS system performance, and how they may better work together to improve care. This systematic literature review and environmental scan addresses NAM's recommendations by answering two research questions: (1) what aspects of EMS systems are most measured in the peer-reviewed and grey literatures, and (2) what do these measures and studies suggest for high-quality EMS oversight? To answer these questions, a systematic literature review was conducted in the PubMed (National Center for Biotechnology Information, National Institutes of Health; Bethesda, Maryland USA), Web of Science (Thomson Reuters; New York, New York USA), SCOPUS (Elsevier; Amsterdam, Netherlands), and EMBASE (Elsevier; Amsterdam, Netherlands) databases for peer-reviewed literature and for grey literature; targeted web searches of 10 EMS-related government agencies and professional organizations were performed. Inclusion criteria required peer-reviewed literature to be published between 1966-2016 and grey literature to be published between 1996-2016. A total of 1,476 peer-reviewed titles were reviewed, 76 were retrieved for full-text review, and 58 were retained and coded in the qualitative software Dedoose (Manhattan Beach, California USA) using a codebook of themes. Categorizations of measure type and level of application were assigned to the extracted data. Targeted websites were systematically reviewed and 115 relevant grey literature documents were retrieved. A total of 58 peer-reviewed articles met inclusion

The Impact of Language and Culture Diversity in Occupational Safety.

Science.gov (United States)

De Jesus-Rivas, Mayra; Conlon, Helen Acree; Burns, Candace

2016-01-01

Occupational health nursing plays a critical part in improving the safety of foreign labor workers. The development and implementation of safety training programs do not always regularly take into account language barriers, low literacy levels, or cultural elements. This oversight can lead to more injuries and fatalities among this group. Despite established health and safety training programs, a significant number of non-native English speakers are injured or killed in preventable, occupation-related accidents. Introducing safety programs that use alternative teaching strategies such as pictograms, illustrations, and hands-on training opportunities will assist in addressing challenges for non-English laborers. Occupational health nursing has an opportunity to provide guidance on this subject and assist businesses in creating a safer and more productive work environment. © 2015 The Author(s).

Romania - NPP PLiM Between Regulatory Requirement / Oversight and Operator Safety / Financial Interest

International Nuclear Information System (INIS)

Goicea, Lucian

2012-01-01

Cernavoda Unit 1 PLiM started in the first third of its design life, to develop as regulatory requirements of the components of standards and programmes and to benefit by earlier implementation of the measures for achieving maximum operating life. CNCAN regulatory present approach on the utility PLiM combines the regulatory requirements on management system, ageing management provisions of periodic safety review, detailed technical requirements of ageing programmes and different techniques focusing only on safety issues. (author)

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.

Oversight of the Air Force - What is the Audit Component and How Can Air Force Managers Deal with It Effectively?

Science.gov (United States)

1988-05-01

This report discusses authority, mission, and responsibilities of the audit organizations that perform oversight of Air Force operations. A...the discussion of the major audit organizations. The audit oversight function is here to stay. Auditors and audit organizations can be beneficial to Air

The oversight of nuclear safety - a mission in the service of the public

International Nuclear Information System (INIS)

Melin, J.

2001-01-01

A country introducing nuclear power in their energy strategy has a life long obligation to the public. The obligation is not a question of energy production. It is an obligation to maintain safety during the phase of construction, energy production as well as for the disposal of waste and spent fuel. One part of this obligation and responsibility to the public is a matter of trust. A responsible government should never accept that fear related to Nuclear Power is a lack in trust. Trust can never be regulated or forced upon the public. Trust is something you have to earn. We must remember that we as Nuclear Safety Regulators have a mission in the service of the public. We are by the public seen as guarantor for the safety of Nuclear Installations in our countries. Our aim must be that the public is trusting that our work will lead to a safe operation of Nuclear Installations. (author)

Regulatory oversight report 2016 concerning nuclear safety in Swiss nuclear installations

International Nuclear Information System (INIS)

2017-06-01

ENSI, the Swiss Federal Nuclear Safety Inspectorate, assesses and monitors safety in the Swiss nuclear facilities. These include the five nuclear power plants: Beznau Units 1 and 2 (KKB1 and KKB2), Muehleberg (KKM), Goesgen (KKG) and Leibstadt (KKL), the interim storage facilities based at each plant, the Central Interim Storage Facility (Zwilag) in Wuerenlingen together with the nuclear facilities at the Paul Scherrer Institute (PSI), the University of Basel (UniB) and the Federal Institute of Technology in Lausanne (EPFL). Using a combination of inspections, regulatory meetings, checks, analyses and the reporting of the operators of individual facilities, ENSI obtains the required overview of nuclear safety in these facilities. It ensures that they operate as required by law. ENSI's regulatory responsibilities also include the transport of radioactive materials from and to nuclear facilities and preparations for a deep geological repository for radioactive waste. ENSI maintains its own emergency organisation, which is an integral part of the national emergency structure that would be activated in the event of a serious incident at a nuclear facility in Switzerland. ENSI reports periodically on its supervisory activities. It informs the public about special events and findings in the nuclear installations. All five nuclear power plants in Switzerland operated safely during the past year. Nuclear safety at all plants in operation was rated as good or satisfactory. In 2016, there were 31 reportable events at the nuclear power plants. 30 events were rated Level 0 (event of no or low safety significance) on the International Nuclear and Radiological Event Scale (INES) and one was rated Level 1 (anomaly) at KKL. Zwilag consists of several interim storage buildings, a conditioning plant and a plasma plant (incineration/melting plant). At the end of 2016, the cask storage hall contained 56 transport/storage casks with spent fuel assemblies and vitrified residue

17 CFR 240.19d-4 - Notice by the Public Company Accounting Oversight Board of disapproval of registration or of...

Science.gov (United States)

2010-04-01

... Accounting Oversight Board of disapproval of registration or of disciplinary action. (a) Definitions—(1... Accounting Oversight Board of disapproval of registration or of disciplinary action. 240.19d-4 Section 240.19d-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES...

48 CFR 936.609-3 - Work oversight in architect-engineer contracts.

Science.gov (United States)

2010-10-01

... architect-engineer contracts. 936.609-3 Section 936.609-3 Federal Acquisition Regulations System DEPARTMENT OF ENERGY SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Architect-Engineer Services 936.609-3 Work oversight in architect-engineer contracts. In addition to the clause at 48...

Long-Term Safety of Drug-Eluting and Bare-Metal Stents

DEFF Research Database (Denmark)

Palmerini, Tullio; Benedetto, Umberto; Biondi-Zoccai, Giuseppe

2015-01-01

BACKGROUND: Previous meta-analyses have investigated the relative safety and efficacy profiles of different types of drug-eluting stents (DES) and bare-metal stents (BMS); however, most prior trials in these meta-analyses reported follow-up to only 1 year, and as such, the relative long-term safety....... RESULTS: Fifty-one trials that included a total of 52,158 randomized patients with follow-up duration ≥3 years were analyzed. At a median follow-up of 3.8 years, cobalt-chromium everolimus-eluting stents (EES) were associated with lower rates of mortality, definite stent thrombosis (ST), and myocardial...... infarction than BMS, paclitaxel-eluting stents (PES), and sirolimus-eluting stents (SES) and less ST than BES. Phosphorylcholine-based zotarolimus-eluting stents had lower rates of definite ST than SES and lower rates of myocardial infarction than BMS and PES. The late rates of target...

Effects of Prescription Drugs During Pregnancy. Hearing Before the Subcommittee on Investigations and Oversight of the Committee on Science and Technology, U.S. House of Representatives, Ninety-Seventh Congress, First Session (July, 30, 1981).

Science.gov (United States)

Congress of the U.S., Washington, DC. House Committee on Science and Technology.

This hearing focuses on scientific and policy deficiencies in the area of drug-induced birth defects. Witnesses charge that (1) the Food and Drug Administration (FDA) does not require the kinds of clinical studies that are necessary to actually determine the safety of drugs used in pregnancy, (2) the FDA does nothing to enable women to find out…

Upgrading the safety toolkit: Initiatives of the accident analysis subgroup

International Nuclear Information System (INIS)

O'Kula, K.R.; Chung, D.Y.

1999-01-01

Since its inception, the Accident Analysis Subgroup (AAS) of the Energy Facility Contractors Group (EFCOG) has been a leading organization promoting development and application of appropriate methodologies for safety analysis of US Department of Energy (DOE) installations. The AAS, one of seven chartered by the EFCOG Safety Analysis Working Group, has performed an oversight function and provided direction to several technical groups. These efforts have been instrumental toward formal evaluation of computer models, improving the pedigree on high-use computer models, and development of the user-friendly Accident Analysis Guidebook (AAG). All of these improvements have improved the analytical toolkit for best complying with DOE orders and standards shaping safety analysis reports (SARs) and related documentation. Major support for these objectives has been through DOE/DP-45

Determination of Safety Performance Grade of NPP Using Integrated Safety Performance Assessment (ISPA) Program

International Nuclear Information System (INIS)

Chung, Dae Wook

2011-01-01

Since the beginning of 2000, the safety regulation of nuclear power plant (NPP) has been challenged to be conducted more reasonable, effective and efficient way using risk and performance information. In the United States, USNRC established Reactor Oversight Process (ROP) in 2000 for improving the effectiveness of safety regulation of operating NPPs. The main idea of ROP is to classify the NPPs into 5 categories based on the results of safety performance assessment and to conduct graded regulatory programs according to categorization, which might be interpreted as 'Graded Regulation'. However, the classification of safety performance categories is highly comprehensive and sensitive process so that safety performance assessment program should be prepared in integrated, objective and quantitative manner. Furthermore, the results of assessment should characterize and categorize the actual level of safety performance of specific NPP, integrating all the substantial elements for assessing the safety performance. In consideration of particular regulatory environment in Korea, the integrated safety performance assessment (ISPA) program is being under development for the use in the determination of safety performance grade (SPG) of a NPP. The ISPA program consists of 6 individual assessment programs (4 quantitative and 2 qualitative) which cover the overall safety performance of NPP. Some of the assessment programs which are already implemented are used directly or modified for incorporating risk aspects. The others which are not existing regulatory programs are newly developed. Eventually, all the assessment results from individual assessment programs are produced and integrated to determine the safety performance grade of a specific NPP

Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

Science.gov (United States)

Castleden, C M; Pickles, H

1988-10-01

1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age.

Technical oversight for installation of TNX piezometers, Final Report

Energy Technology Data Exchange (ETDEWEB)

Pidcoe, W.W. Jr. [Westinghouse Savannah River Company, Aiken, SC (United States)

1997-06-05

Science Applications International Corporation was tasked under subcontract C002025P to provide technical oversight for the drilling of one pilot borehole, and the drilling and installation of five piezometers in the TNX Area Swamp. The work was performed in accordance with the Statement of Work in Task Order Proposal No. ER39-129 dated August 6, 1996. This report describes the activities associated with the performance of the task.

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

Directory of Open Access Journals (Sweden)

Roth SH

2011-05-01

Full Text Available Sanford H RothArizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.Keywords: NSAIDs, osteoarthritis, topical administration, synovial fluid, peptic ulcer, Helicobacter pylori

Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.

Science.gov (United States)

Trelle, Sven; Reichenbach, Stephan; Wandel, Simon; Hildebrand, Pius; Tschannen, Beatrice; Villiger, Peter M; Egger, Matthias; Jüni, Peter

2011-01-11

To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Network meta-analysis. Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

[Drug supply chain safety in hospitals: current data and experience of the Grenoble university hospital].

Science.gov (United States)

Bedouch, P; Baudrant, M; Detavernier, M; Rey, C; Brudieu, E; Foroni, L; Allenet, B; Calop, J

2009-01-01

Drug supply chain safety has become a priority for public health which implies a collective process. This process associates all health professionals including the pharmacist who plays a major role. The objective of this present paper is to describe the several approaches proven effective in the reduction of drug-related problem in hospital, illustrated by the Grenoble University Hospital experience. The pharmacist gets involved first in the general strategy of hospital drug supply chain, second by his direct implication in clinical activities. The general strategy of drug supply chain combines risk management, coordination of the Pharmacy and Therapeutics Committee, selection and purchase of drugs and organisation of drug supply chain. Computer management of drug supply chain is a major evolution. Nominative drug delivering has to be a prior objective and its implementation modalities have to be defined: centralized or decentralized in wards, manual or automated. Also, new technologies allow the automation of overall drug distribution from central pharmacy and the implementation of automated drug dispensing systems into wards. The development of centralised drug preparation allows a safe compounding of high risk drugs, like cytotoxic drugs. The pharmacist should develop his clinical activities with patients and other health care professionals in order to optimise clinical decisions (medication review, drug order analysis) and patients follow-up (therapeutic monitoring, patient education, discharge consultation).

Drug safety evaluation of defibrotide.

Science.gov (United States)

Richardson, Paul G; Corbacioglu, Selim; Ho, Vincent Trien-Vinh; Kernan, Nancy A; Lehmann, Leslie; Maguire, Craig; Maglio, Michelle; Hoyle, Margaret; Sardella, Marco; Giralt, Sergio; Holler, Ernst; Carreras, Enric; Niederwieser, Dietger; Soiffer, Robert

2013-01-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD). None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions. This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases. The literature review was conducted using a PubMed search with the fixed term 'defibrotide' in combination with ≥ 1 of 'safety', 'veno-occlusive disease' (with and without 'treatment', 'prevention'), 'oncology', 'myeloma', 'microangiopathy', 'anti-thrombotic' and 'peripheral vascular disorder'. Related articles from the EBMT and ASH conference websites were also included. DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD.

Safety and effectiveness of drug therapy for the acutely agitated patient (Part 2

Directory of Open Access Journals (Sweden)

Gianluca Airoldi

2013-04-01

Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the second in a 2-part series is to review published data on the efficacy and safety of antipsychotic medications currently available for managing situations of this type. Arrhythmias caused by QT-prolonging drugs occur infrequently, and multiple factors are often involved, including concomitant use of other drugs affecting the same pathway (most antipsychotic drugs prolong the QT interval by blocking potassium IKr current in HERG channels of myocardial cells, electrolyte disorders and, possibly, genetic predisposition. Judicious use of typical antipsychotics (mainly haloperidol and benzodiazepines (mainly lorazepam, given intramuscularly alone or in combination, has proved to be safe and effective for controlling acute motor agitation related to psychiatric illness; cocaine, methamphetamine, and ethanol toxicity; ethanol withdrawal; and other factors. They are still widely used and are particularly useful when limited data are available on the patient’s history of cardiovascular disease, current use of medication, and/or the likelihood of illicit drug or alcohol intoxication; when the diagnosis involves medical comorbidity or intoxication; or when there is no specific treatment (e.g., personality disorders, learning disabilities, mental retardation, organic brain damage. If rapid tranquillization is necessary before a formal diagnosis can be made and there are uncertainties regarding the patient’s medical history, lorazepam is often considered the first-line drug of choice. In

Holes in the safety net: a case study of access to prescription drugs and specialty care.

Science.gov (United States)

Stanley, Ava; Cantor, Joel C; Guarnaccia, Peter

2008-07-01

The health care safety net in the United States is intended to fill gaps in health care services for uninsured and other vulnerable populations. This paper presents a case study of New Brunswick, NJ, a small city rich in safety net resources, to examine the adequacy of the American model of safety net care. We find substantial gaps in access to care despite the presence of a medical school, an abundance of primary care and specialty physicians, two major teaching hospitals, a large federally qualified health center and other safety net resources in this community of about 50,000 residents. Using a blend of random-digit-dial and area probability sampling, a survey of 595 households was conducted in 2001 generating detailed information about the health, access to care, demographic and other characteristics of 1,572 individuals. Confirming the great depth of the New Brunswick health care safety net, the survey showed that more than one quarter of local residents reported a hospital or community clinic as their usual source of care. Still, barriers to prescription drugs were reported for 11.0% of the area population and more than two in five (42.8%) local residents who perceived a need for specialty care reported difficulty getting those services. Bivariate analyses show significantly elevated risk of access problems among Hispanic and black residents, those in poor health, those relying on hospital and community clinics or with no usual source of care, and those living at or below poverty. In multivariate analysis, lack of health insurance was the greatest risk factor associated with both prescription drug and specialty access problems. Few local areas can claim the depth of safety net resources as New Brunswick, NJ, raising serious concerns about the adequacy of the American safety net model, especially for people with complex and chronic health care needs.

AGB Statement on Board Responsibility for the Oversight of Educational Quality

Science.gov (United States)

Association of Governing Boards of Universities and Colleges, 2011

2011-01-01

This "Statement on Board Responsibility for the Oversight of Educational Quality," approved by the Board of Directors of the Association of Governing Boards (AGB) in March 2011, urges institutional administrators and governing boards to engage fully in this area of board responsibility. The seven principles in this statement offer suggestions to…

Building Nuclear Safety and Security Culture Within Regulatory Body

International Nuclear Information System (INIS)

Huda, K.

2016-01-01

To achieve a higher level of nuclear safety and security, it needs to develop the safety and security culture not only in the facility but also in the regulatory body. The regulatory body, especially needs to develop the safety and security culture within the organization, because it has a function to promote and oversee the culture in the facilities. In this sense, the regulatory body should become a role model. Development of the nuclear safety and security culture should be started by properly understanding its concept and awakening the awareness of individual and organization on the importance of nuclear safety and security. For effectiveness of the culture development in the regulatory body, the following steps are suggested to be taken: setting up of the regulatory requirements, self-assessment, independent assessment review, communication with the licensee, oversight of management system implementation, and integration with regulatory activities. The paper discusses those steps in the framework of development of nuclear safety and security culture in the regulatory body, as well as some important elements in building of the culture in the nuclear facilities. (author)

Epigenetics and cancer: implications for drug discovery and safety assessment

International Nuclear Information System (INIS)

Moggs, Jonathan G.; Goodman, Jay I.; Trosko, James E.; Roberts, Ruth A.

2004-01-01

It is necessary to determine whether chemicals or drugs have the potential to pose a threat to human health. Research conducted over the last two decades has led to the paradigm that chemicals can cause cancer either by damaging DNA or by altering cellular growth, probably via receptor-mediated changes in gene expression. However, recent evidence suggests that gene expression can be altered markedly via several diverse epigenetic mechanisms that can lead to permanent or reversible changes in cellular behavior. Key molecular events underlying these mechanisms include the alteration of DNA methylation and chromatin, and changes in the function of cell surface molecules. Thus, for example, DNA methyltransferase enzymes together with chromatin-associated proteins such as histone modifying enzymes and remodelling factors can modify the genetic code and contribute to the establishment and maintenance of altered epigenetic states. This is relevant to many types of toxicity including but not limited to cancer. In this paper, we describe the potential for interplay between genetic alteration and epigenetic changes in cell growth regulation and discuss the implications for drug discovery and safety assessment

Predictive toxicology in drug safety

National Research Council Canada - National Science Library

Xu, Jinghai J; Urban, Laszlo

2011-01-01

.... It provides information on the present knowledge of drug side effects and their mitigation strategy during drug discovery, gives guidance for risk assessment, and promotes evidence-based toxicology...

Safety of Therapeutic Fever Induction in Cancer Patients Using Approved PAMP Drugs

Directory of Open Access Journals (Sweden)

Uwe Rudolf Max Reuter

2018-04-01

Full Text Available William Coley, between 1895 and 1936, treated hundreds of cancer patients using infusions of fever inducing bacerial extracts. Similar experiments were done by Klyuyeva and co-workers in the 1940ies in Russia using trypanosoma extracts. Many remissions and cures were reported. We have conjectured that pathogen associated molecular pattern substances (PAMP are the molecular explanation for the beneficial treatments in both groups. We could show that a combination of PAMP can eradicate solid tumours in cancer mice if applied several times. Accordingly, we suggested to combine PAMP containing approved drugs to treat cancer patients using a protocol similar to the old fever induction regimen. In this retrospective phase-1 study we report on the fever induction capacity and safety of applications of bacterial extracts, combinations of bacterial extracts with approved drugs, and combinations of approved drugs in 131 mainly cancer patients. Adverse reactions were those which can be expected during a feverish infection and mild. Over 523 fever inductions, no severe adverse reaction was observed.

Patient and physician attitudes regarding risk and benefit in streamlined development programmes for antibacterial drugs: a qualitative analysis.

Science.gov (United States)

Holland, Thomas L; Mikita, Stephen; Bloom, Diane; Roberts, Jamie; McCall, Jonathan; Collyar, Deborah; Santiago, Jonas; Tiernan, Rosemary; Toerner, Joseph

2016-11-10

To explore patient, caregiver and physician perceptions and attitudes regarding the balance of benefit and risk in using antibacterial drugs developed through streamlined development processes. Semistructured focus groups and in-depth interviews were conducted to elicit perceptions and attitudes about the use of antibacterial drugs to treat multidrug-resistant infections. Participants were given background information about antibiotic resistance, streamlined drug development programmes and FDA drug approval processes. Audio recordings of focus groups/interviews were reviewed and quotes excerpted and categorised to identify key themes. Two primary stakeholder groups were engaged: one comprising caregivers, healthy persons and patients who had recovered from or were at risk of resistant infection (N=67; 11 focus groups); and one comprising physicians who treat resistant infections (N=23). Responses from focus groups/interviews indicated widespread awareness among patients/caregivers and physicians of the seriousness of the problem of antibacterial resistance. Both groups were willing to accept a degree of uncertainty regarding the balance of risk and benefit in a new therapy where a serious unmet need exists, but also expressed a desire for rigorous monitoring and rapid, transparent reporting of safety/effectiveness data. Both groups wanted to ensure that >1 physician had input on whether to treat patients with antibiotics developed through a streamlined process. Some patients/caregivers unfamiliar with exigencies of critical care suggested a relatively large multidisciplinary team, while physicians believed individual expert consultations would be preferable. Both groups agreed that careful oversight and stewardship of antibacterial drugs are needed to ensure patient safety, preserve efficacy and prevent abuse. Groups comprising patients/caregivers and physicians were aware of serious issues posed by resistant infections and the lack of effective antibacterial drug

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

Science.gov (United States)

Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

2016-12-12

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

Exploiting heterogeneous publicly available data sources for drug safety surveillance: computational framework and case studies.

Science.gov (United States)

Koutkias, Vassilis G; Lillo-Le Louët, Agnès; Jaulent, Marie-Christine

2017-02-01

Driven by the need of pharmacovigilance centres and companies to routinely collect and review all available data about adverse drug reactions (ADRs) and adverse events of interest, we introduce and validate a computational framework exploiting dominant as well as emerging publicly available data sources for drug safety surveillance. Our approach relies on appropriate query formulation for data acquisition and subsequent filtering, transformation and joint visualization of the obtained data. We acquired data from the FDA Adverse Event Reporting System (FAERS), PubMed and Twitter. In order to assess the validity and the robustness of the approach, we elaborated on two important case studies, namely, clozapine-induced cardiomyopathy/myocarditis versus haloperidol-induced cardiomyopathy/myocarditis, and apixaban-induced cerebral hemorrhage. The analysis of the obtained data provided interesting insights (identification of potential patient and health-care professional experiences regarding ADRs in Twitter, information/arguments against an ADR existence across all sources), while illustrating the benefits (complementing data from multiple sources to strengthen/confirm evidence) and the underlying challenges (selecting search terms, data presentation) of exploiting heterogeneous information sources, thereby advocating the need for the proposed framework. This work contributes in establishing a continuous learning system for drug safety surveillance by exploiting heterogeneous publicly available data sources via appropriate support tools.

Consumer Mobile Apps for Potential Drug-Drug Interaction Check: Systematic Review and Content Analysis Using the Mobile App Rating Scale (MARS).

Science.gov (United States)

Kim, Ben Yb; Sharafoddini, Anis; Tran, Nam; Wen, Emily Y; Lee, Joon

2018-03-28

General consumers can now easily access drug information and quickly check for potential drug-drug interactions (PDDIs) through mobile health (mHealth) apps. With aging population in Canada, more people have chronic diseases and comorbidities leading to increasing numbers of medications. The use of mHealth apps for checking PDDIs can be helpful in ensuring patient safety and empowerment. The aim of this study was to review the characteristics and quality of publicly available mHealth apps that check for PDDIs. Apple App Store and Google Play were searched to identify apps with PDDI functionality. The apps' general and feature characteristics were extracted. The Mobile App Rating Scale (MARS) was used to assess the quality. A total of 23 apps were included for the review-12 from Apple App Store and 11 from Google Play. Only 5 of these were paid apps, with an average price of $7.19 CAD. The mean MARS score was 3.23 out of 5 (interquartile range 1.34). The mean MARS scores for the apps from Google Play and Apple App Store were not statistically different (P=.84). The information dimension was associated with the highest score (3.63), whereas the engagement dimension resulted in the lowest score (2.75). The total number of features per app, average rating, and price were significantly associated with the total MARS score. Some apps provided accurate and comprehensive information about potential adverse drug effects from PDDIs. Given the potentially severe consequences of incorrect drug information, there is a need for oversight to eliminate low quality and potentially harmful apps. Because managing PDDIs is complex in the absence of complete information, secondary features such as medication reminder, refill reminder, medication history tracking, and pill identification could help enhance the effectiveness of PDDI apps. ©Ben YB Kim, Anis Sharafoddini, Nam Tran, Emily Y Wen, Joon Lee. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 28.03.2018.

Nuclear Protections and Safety Act of 1987. Report of the Committee on Governmental Affairs, United States Senate together with Additional Views to Accompany S. 1085, One Hundredth Congress, First Session

International Nuclear Information System (INIS)

Anon.

1987-01-01

The Senate report on S. 1085 suggests several amendments to the recommended bill which would make oversight of nuclear facility safety an independent board. The legislation responds to concerns that there is no justification for DOE facilities to be exempt from this kind of oversight, and that health and safety standards are as important at nuclear weapons and materials facilities as elsewhere. The report traces the emergence of the nuclear age and the different treatment of government and commercial facilities. There is evidence of a lack of concern for employee health and safety at some government installations. The report summarizes the four titles of the bill, reviews the four days of public hearings, and analyzes the bill by section. It notes changes that will result in the Energy Reorganization Act of 1974, the Atomic Energy Act of 1954, and the Department of Energy Organization Act

78 FR 23273 - Determination That the OXYCONTIN (Oxycodone Hydrochloride) Drug Products Covered by New Drug...

Science.gov (United States)

2013-04-18

... mitigation strategy (REMS) http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationfor... Blueprint for Prescriber Education for Extended- Release and Long-Acting Opioid Analgesics'' ( http://www...

Review of the Methods to Obtain Paediatric Drug Safety Information: Spontaneous Reporting and Healthcare Databases, Active Surveillance Programmes, Systematic Reviews and Meta-analyses

Science.gov (United States)

Gentili, Marta; Pozzi, Marco; Peeters, Gabrielle; Radice, Sonia; Carnovale, Carla

2018-02-06

Knowledge of drugs safety collected during the pre-marketing phase is inevitably limited because the randomized clinical trials (RCTs) are rarely designed to evaluate safety. The small and selective groups of enrolled individuals and the limited duration of trials may hamper the ability to characterize fully the safety profiles of drugs. Additionally, information about rare adverse drug reactions (ADRs) in special groups is often incomplete or not available for most of the drugs commonly used in the daily clinical practice. In the paediatric setting several highimpact safety issues have emerged. Hence, in recent years, there has been a call for improved post-marketing pharmacoepidemiological studies, in which cohorts of patients are monitored for sufficient time in order to determine the precise risk-benefit ratio. In this review, we discuss the current available strategies enhancing the post-marketing monitoring activities of the drugs in the paediatric setting and define criteria whereby they can provide valuable information to improve the management of therapy in daily clinical practice including both safety and efficacy aspects. The strategies we cover include the signal detection using international pharmacovigilance and/or healthcare databases, the promotion of active surveillance initiatives which can generate complete, informative data sets for the signal detection and systematic review/meta-analysis. Together, these methods provide a comprehensive picture of causality and risk improving the management of therapy in a paediatric setting and they should be considered as a unique tool to be integrated with post-marketing activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events analysis.

Science.gov (United States)

Giofrè, Chiara; Scicchitano, Francesca; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; Leporini, Christian; Ventrice, Pasquale; Carbone, Claudia; Saullo, Francesca; Rende, Pierandrea; Menniti, Michele; Mumoli, Laura; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

2013-12-01

Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar(®)), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups "41-65" (39.07%) and "over 65" (27.9%) were the most affected. Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.

Pharmacovigilance and drug safety 2011 in Calabria (Italy: Adverse events analysis

Directory of Open Access Journals (Sweden)

Francesca Scicchitano

2012-01-01

Full Text Available Background : Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs. The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. Materials and Methods: We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Results : Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100 in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %. Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%. There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it, and there is a strong interest in participating to training courses in the field (95% are interested. Conclusions : Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis.

Science.gov (United States)

Scicchitano, Francesca; Giofrè, Chiara; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; De Fazio, Salvatore; Menniti, Michele; Curia, Rubens; Arena, Concetta; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

2012-09-01

Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

Beyond Measure: New Approaches to Analyzing Congressional Oversight of Homeland Security

Science.gov (United States)

2015-03-01

published books and peer reviewed journal articles. The Congressional Research Service being the key source on congressional procedure and theory ...Transportation Committee 1 Senate Homeland Security & Governmental Affairs Committee 15 Senate Small Business & Entrepreneurship 1 Senate Special...military contracting procedures in a war zone are not necessarily oversight of national security functions, reviews of FEMA contracting practices

Real-time Responsiveness for Ethics Oversight During Disaster Research.

Science.gov (United States)

Eckenwiler, Lisa; Pringle, John; Boulanger, Renaud; Hunt, Matthew

2015-11-01

Disaster research has grown in scope and frequency. Research in the wake of disasters and during humanitarian crises--particularly in resource-poor settings--is likely to raise profound and unique ethical challenges for local communities, crisis responders, researchers, and research ethics committees (RECs). Given the ethical challenges, many have questioned how best to provide research ethics review and oversight. We contribute to the conversation concerning how best to ensure appropriate ethical oversight in disaster research and argue that ethical disaster research requires of researchers and RECs a particular sort of ongoing, critical engagement which may not be warranted in less exceptional research. We present two cases that typify the concerns disaster researchers and RECs may confront, and elaborate upon what this ongoing engagement might look like--how it might be conceptualized and utilized--using the concept of real-time responsiveness (RTR). The central aim of RTR, understood here as both an ethical ideal and practice, is to lessen the potential for research conducted in the wake of disasters to create, perpetuate, or exacerbate vulnerabilities and contribute to injustices suffered by disaster-affected populations. Well cultivated and deployed, we believe that RTR may enhance the moral capacities of researchers and REC members, and RECs as institutions where moral agency is nurtured and sustained. © 2015 John Wiley & Sons Ltd.

Political and Budgetary Oversight of the Ukrainian Intelligence Community: Processes, Problems and Prospects for Reform

National Research Council Canada - National Science Library

Petrov, Oleksii

2007-01-01

This thesis addresses the problem of providing policy and budget oversight of Ukrainian intelligence organizations in accordance with norms and practices developed in contemporary Western democracies...

The Internet and drug safety: what are the implications for pharmacovigilance?

Science.gov (United States)

Cobert, B; Silvey, J

1999-02-01

Use of the Internet is becoming widespread throughout the world. Its use in the domain of drug safety and pharmacovigilance is spreading rapidly. Governments and industry have taken the lead in developing extensive web sites. The US Food and Drug Administration (FDA), the European Agency for the Evaluation of Medicinal Products (EMEA) and other agencies have developed sites containing enormous amounts of information both on pharmacovigilance in general and on specific drugs in particular. Under the US 'Freedom of Information Act' the FDA has put major parts of its adverse event database on line. Regulatory documents are also available from the FDA site or from hyperlinks described in the site. The US Center for Drug Evaluation and Research updates its site most days and maintains a free automated e-mail announcement service of these updates. Similarly, the EMEA updates its site frequently and publishes extensive material including regulatory documents, guidelines, European Public Assessment Reports on newly approved medications and other useful information. A free update service by e-mail is also available. Although English is the primary language used on the EMEA site, some of the information is available in other languages. Pharmaceutical companies are not using the Internet for pharmacovigilance yet. Rather, the Internet is being used for promotion of their products and for informing consumers on general information on diseases, for financial and investor data and for employment opportunities, etc. Other organisations such as lobbies, consumer groups and medical journals are also beginning to use the Internet. The electronic transmission of safety information, using the standards developed by the International Conference on Harmonization, is currently being tested for the transmission of individual patient adverse event information between companies and governments. In addition, the FDA has begun to accept adverse events from healthcare providers and consumers

Permitting product liability litigation for FDA-approved drugs and devices promotes patient safety.

Science.gov (United States)

Kesselheim, A S

2010-06-01

In 2008 and 2009, the Supreme Court reviewed the question of whether patients injured by dangerous prescription drugs or medical devices can bring tort lawsuits against pharmaceutical and device manufacturers. The Court ruled that claims against device manufacturers were preempted while claims against pharmaceutical manufacturers were not. The threat of product liability lawsuits promotes patient safety by encouraging manufacturers to take greater responsibility in providing clear warnings about known adverse effects of their products.

VVER Reactor Safety in Eastern Europe and Former Soviet Union

Science.gov (United States)

Papadopoulou, Demetra

2012-02-01

VVER Soviet-designed reactors that operate in Eastern Europe and former Soviet republics have heightened international concern for years due to major safety deficiencies. The governments of countries with VVER reactors have invested millions of dollars toward improving the safety of their nuclear power plants. Most of these reactors will continue to operate for the foreseeable future since they provide urgently-needed electrical power. Given this situation, this paper assesses the radiological consequences of a major nuclear accident in Eastern Europe. The paper also chronicles the efforts launched by the international nuclear community to improve the safety of the reactors and notes the progress made so far through extensive collaborative efforts in Armenia, Bulgaria, the Czech Republic, Hungary, Kazakhstan, Lithuania, Russia, Slovakia, and Ukraine to reduce the risks of nuclear accidents. Western scientific and technical staff collaborated with these countries to improve the safety of their reactor operations by strengthening the ability of the regulator to perform its oversight function, installing safety equipment and technologies, investing time in safety training, and working diligently to establish an enduring safety culture. Still, continued safety improvement efforts are necessary to ensure safe operating practices and achieve timely phase-out of older plants.

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

Directory of Open Access Journals (Sweden)

Rosângela Teixeira

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

Directory of Open Access Journals (Sweden)

Rosângela Teixeira

2013-04-01

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Evaluation of Electronic Healthcare Databases for Post-Marketing Drug Safety Surveillance and Pharmacoepidemiology in China.

Science.gov (United States)

Yang, Yu; Zhou, Xiaofeng; Gao, Shuangqing; Lin, Hongbo; Xie, Yanming; Feng, Yuji; Huang, Kui; Zhan, Siyan

2018-01-01

Electronic healthcare databases (EHDs) are used increasingly for post-marketing drug safety surveillance and pharmacoepidemiology in Europe and North America. However, few studies have examined the potential of these data sources in China. Three major types of EHDs in China (i.e., a regional community-based database, a national claims database, and an electronic medical records [EMR] database) were selected for evaluation. Forty core variables were derived based on the US Mini-Sentinel (MS) Common Data Model (CDM) as well as the data features in China that would be desirable to support drug safety surveillance. An email survey of these core variables and eight general questions as well as follow-up inquiries on additional variables was conducted. These 40 core variables across the three EHDs and all variables in each EHD along with those in the US MS CDM and Observational Medical Outcomes Partnership (OMOP) CDM were compared for availability and labeled based on specific standards. All of the EHDs' custodians confirmed their willingness to share their databases with academic institutions after appropriate approval was obtained. The regional community-based database contained 1.19 million people in 2015 with 85% of core variables. Resampled annually nationwide, the national claims database included 5.4 million people in 2014 with 55% of core variables, and the EMR database included 3 million inpatients from 60 hospitals in 2015 with 80% of core variables. Compared with MS CDM or OMOP CDM, the proportion of variables across the three EHDs available or able to be transformed/derived from the original sources are 24-83% or 45-73%, respectively. These EHDs provide potential value to post-marketing drug safety surveillance and pharmacoepidemiology in China. Future research is warranted to assess the quality and completeness of these EHDs or additional data sources in China.

Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

International Nuclear Information System (INIS)

Prueksaritanont, Thomayant; Lin, Jiunn H.; Baillie, Thomas A.

2006-01-01

This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models

Insight and Lessons Learned on Safety Culture from Analysis of Inspection Findings and Events

International Nuclear Information System (INIS)

Kim, J.T.; Jung, S.J.; Choi, Y.S.

2016-01-01

Safety culture has been a main subject of scrutiny in major accidents of modern complex technologies. The Fukushima accident also plausibly has its root cause deep into weak safety culture. After the Fukushima accident in Japan 2011, many critics have searched for cultural factors that caused the unacceptable negligence pervaded in Japan’s nuclear society. Renewed emphasis has also been placed on rebuilding strong safety culture by operators, regulators, and relevant institutions worldwide. Significant progress has been made in approach to safety culture and this led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety.

[RADIATION SAFETY DURING REMEDIATION OF THE "SEVRAO" FACILITIES].

Science.gov (United States)

Shandala, N K; Kiselev, S M; Titov, A V; Simakov, A V; Seregin, V A; Kryuchkov, V P; Bogdanova, L S; Grachev, M I

2015-01-01

Within a framework of national program on elimination of nuclear legacy, State Corporation "Rosatom" is working on rehabilitation at the temporary waste storage facility at Andreeva Bay (Northwest Center for radioactive waste "SEVRAO"--the branch of "RosRAO"), located in the North-West of Russia. In the article there is presented an analysis of the current state of supervision for radiation safety of personnel and population in the context of readiness of the regulator to the implementation of an effective oversight of radiation safety in the process of radiation-hazardous work. Presented in the article results of radiation-hygienic monitoring are an informative indicator of the effectiveness of realized rehabilitation measures and characterize the radiation environment in the surveillance zone as a normal, without the tendency to its deterioration.

Ayurpharmacoepidemiology en Route to Safeguarding Safety and Efficacy of Ayurvedic Drugs in Global Outlook

Science.gov (United States)

Debnath, Parikshit; Banerjee, Subhadip; Adhikari, Anjan; Debnath, Pratip K.

2016-01-01

Ayurpharmacoepidemiology is a new field developed by synergy of the fields of clinical pharmacology, epidemiology, and ayurveda. It will use the effects of ayurvedic medicinal products on large populations to describe and analyze the practices, evaluate the safety and efficacy, and carry out medicoeconomic evaluations. Good pharmacoepidemiology practices in ayurveda is projected to assist with issues of ayurpharmacoepidemiologic research. The embraced good pharmacoepidemiology practices guideline in this viewpoint will be able to provide valuable evidence about the health effects of ayurvedic herbs/drugs and consider different fields like pharmacovigilance, pharmacoeconomics, and drug discovery with ayurvedic reverse pharmacology approach, also pass out significant data for further basic sciences study in ayurveda biology, ayurgenomics, ayurnutrigenomics, and systems biology. Several unanswered questions about ayurvedic drug use and informed interventions or policies that can be addressed by informatics database, which will eventually demonstrate the credibility and rationality of ayurceuticals in the future. PMID:26721554

Safety and effectiveness of drug therapy for the acutely agitated patient (Part I

Directory of Open Access Journals (Sweden)

Gianluca Airoldi

2013-04-01

Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the first in a 2-part series is to review the extensive safety data published on the antipsychotic medications currently available for managing situations of this type, including older neuroleptics like haloperidol, chlorpromazine, and pimozide as well as a number of the newer atypical antipsychotics (olanzapine, risperidone, ziprasidone. Particular attention is focused on the ability of these drugs to lengthen the QT interval in surface electrocardiograms. This adverse effect is of major concern, especially in light of the reported relation between QT interval and the risk of sudden death. In patients with the congenital long-QT syndrome, a long QT interval is associated with a fatal paroxysmal ventricular arrhythmia knownas torsades de pointes. Therefore, careful evaluation of the QT-prolonging properties and arrhythmogenic potential of antipsychotic drugs is urgently needed. Clinical assessment of drug-induced QT-interval prolongation is strictly dependent on the quality of electrocardiographic data and the appropriateness of electrocardiographic analyses. Unfortunately, measurement imprecision and natural variability preclude a simple use of the actually measured QT interval as a surrogate marker of drug-induced proarrhythmia. Because the QT interval changes with heart rate, a rate-corrected QT interval (QTc is commonly used when evaluating a drug’s effect. In clinical settings, themost widely used formulas for rate-correction are those of Bazett (QTc=QT/RR^0.5 and Fridericia

Deterministic Safety Analysis for Nuclear Power Plants. Specific Safety Guide (Spanish Edition)

International Nuclear Information System (INIS)

2012-01-01

The IAEA's Statute authorizes the Agency to establish safety standards to protect health and minimize danger to life and property - standards which the IAEA must use in its own operations, and which a State can apply by means of its regulatory provisions for nuclear and radiation safety. A comprehensive body of safety standards under regular review, together with the IAEA's assistance in their application, has become a key element in a global safety regime. In the mid-1990s, a major overhaul of the IAEA's safety standards programme was initiated, with a revised oversight committee structure and a systematic approach to updating the entire corpus of standards. The new standards that have resulted are of a high calibre and reflect best practices in Member States. With the assistance of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its safety standards. Safety standards are only effective, however, if they are properly applied in practice. The IAEA's safety services - which range in scope from engineering safety, operational safety, and radiation, transport and waste safety to regulatory matters and safety culture in organizations - assist Member States in applying the standards and appraise their effectiveness. These safety services enable valuable insights to be shared and I continue to urge all Member States to make use of them. Regulating nuclear and radiation safety is a national responsibility, and many Member States have decided to adopt the IAEA's safety standards for use in their national regulations. For the contracting parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the conventions. The standards are also applied by designers, manufacturers and operators around the world to enhance nuclear and radiation safety in power generation, medicine, industry, agriculture, research and education

Political and Budgetary Oversight of the Ukrainian Intelligence Community: Processes, Problems and Prospects for Reform

National Research Council Canada - National Science Library

Petrov, Oleksii

2007-01-01

.... Official government documents, news reports and other literature on the intelligence system in Ukraine, as well as studies of intelligence oversight within democracies are the primary sources of data...

The complications of controlling agency time discretion: FDA review deadlines and postmarket drug safety.

Science.gov (United States)

Carpenter, Daniel; Chattopadhyay, Jacqueline; Moffitt, Susan; Nall, Clayton

2012-01-01

Public agencies have discretion on the time domain, and politicians deploy numerous policy instruments to constrain it. Yet little is known about how administrative procedures that affect timing also affect the quality of agency decisions. We examine whether administrative deadlines shape decision timing and the observed quality of decisions. Using a unique and rich dataset of FDA drug approvals that allows us to examine decision timing and quality, we find that this administrative tool induces a piling of decisions before deadlines, and that these “just-before-deadline” approvals are linked with higher rates of postmarket safety problems (market withdrawals, severe safety warnings, safety alerts). Examination of data from FDA advisory committees suggests that the deadlines may impede quality by impairing late-stage deliberation and agency risk communication. Our results both support and challenge reigning theories about administrative procedures, suggesting they embody expected control-expertise trade-offs, but may also create unanticipated constituency losses.

Drug monitoring in child and adolescent psychiatry for improved efficacy and safety of psychopharmacotherapy

Directory of Open Access Journals (Sweden)

Fegert Jörg M

2009-04-01

Full Text Available Abstract Most psychotropic drugs used in the treatment of children and adolescents are applied "off label" with a direct risk of under- or overdosing and a delayed risk of long-term side effects. The selection of doses in paediatric psychiatric patients requires a consideration of pharmacokinetic parameters and the development of central nervous system, and warrants specific studies in children and adolescents. Because these are lacking for most of the psychotropic drugs applied in the Child and Adolescent and Psychiatry, therapeutic drug monitoring (TDM is a valid tool to optimise pharmacotherapy and to enable to adjust the dosage of drugs according to the characteristics of the individual patient. Multi-centre TDM studies enable the identification of age- and development-dependent therapeutic ranges of blood concentrations and facilitate a highly qualified standardized documentation in the child and adolescent health care system. In addition, they will provide data for future research on psychopharmacological treatment in children and adolescents, as a baseline for example for clinically relevant interactions with various co-medications. Therefore, a German-Austrian-Swiss "Competence Network on Therapeutic Drug Monitoring in Child and Adolescent Psychiatry" was founded 1 introducing a comprehensive internet data base for the collection of demographic, safety and efficacy data as well as blood concentrations of psychotropic drugs in children and adolescents.

Predicting Drug Safety and Communicating Risk: Benefits of a Bayesian Approach.

Science.gov (United States)

Lazic, Stanley E; Edmunds, Nicholas; Pollard, Christopher E

2018-03-01

Drug toxicity is a major source of attrition in drug discovery and development. Pharmaceutical companies routinely use preclinical data to predict clinical outcomes and continue to invest in new assays to improve predictions. However, there are many open questions about how to make the best use of available data, combine diverse data, quantify risk, and communicate risk and uncertainty to enable good decisions. The costs of suboptimal decisions are clear: resources are wasted and patients may be put at risk. We argue that Bayesian methods provide answers to all of these problems and use hERG-mediated QT prolongation as a case study. Benefits of Bayesian machine learning models include intuitive probabilistic statements of risk that incorporate all sources of uncertainty, the option to include diverse data and external information, and visualizations that have a clear link between the output from a statistical model and what this means for risk. Furthermore, Bayesian methods are easy to use with modern software, making their adoption for safety screening straightforward. We include R and Python code to encourage the adoption of these methods.

Effect of Safety Issues with HIV Drugs on the Approval Process of Other Drugs in the Same Class An Analysis of European Public Assessment Reports : an analysis of European public assessment reports

NARCIS (Netherlands)

Arnardottir, Arna H.; Haaijer-Ruskamp, Flora M.; Straus, Sabine M. J.; de Graeff, Pieter A.; Mol, Peter G. M.

2011-01-01

Background: Knowledge on the safety of new medicines is limited at the time of market entry. Nearly half of all drugs used to treat HIV registered in the EU required >= 1 Direct Healthcare Professional Communication (DHPC) in the past 10 years for safety issues identified post-approval. Objective:

Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

Science.gov (United States)

Ocana, Alberto; Ethier, Josee-Lyne; Díez-González, Laura; Corrales-Sánchez, Verónica; Srikanthan, Amirrtha; Gascón-Escribano, María J; Templeton, Arnoud J; Vera-Badillo, Francisco; Seruga, Bostjan; Niraula, Saroj; Pandiella, Atanasio; Amir, Eitan

2015-11-24

Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents. Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed for treatment-related death, treatment-discontinuation related to toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most commonly reported individual AEs were also explored. ORs were pooled in a meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. Seventeen trials (41%) utilized companion diagnostics. Compared to control groups, targeted drugs in experimental arms were associated with increased odds of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of whether they utilized companion diagnostics or not. Compared to drugs without available companion diagnostics, agents with companion diagnostics had a lower magnitude of increased odds of treatment discontinuation (OR = 1.12 vs. 1.65, p diagnostics were greatest for diarrhea (OR = 1.29 vs. 2.43, p diagnostics are associated with improved safety, and tolerability. Differences were most marked for gastrointestinal, cutaneous and neurological toxicity.

'We all want to succeed, but we've also got to be realistic about what is happening': an ethnographic study of relationships in trial oversight and their impact.

Science.gov (United States)

Daykin, Anne; Selman, Lucy E; Cramer, Helen; McCann, Sharon; Shorter, Gillian W; Sydes, Matthew R; Gamble, Carrol; Macefield, Rhiannon; Lane, J Athene; Shaw, Alison

2017-12-22

The oversight and conduct of a randomised controlled trial involves several stakeholders, including a Trial Steering Committee (TSC), Trial Management Group (TMG), Data Monitoring Committee (DMC), funder and sponsor. We aimed to examine how the relationships between these stakeholders affect the trial oversight process and its rigour, to inform future revision of Good Clinical Practice guidelines. Using an ethnographic study design, we observed the oversight processes of eight trials and conducted semi-structured interviews with members of the trials' TSCs and TMGs, plus other relevant informants, including sponsors and funders of trials. Data were analysed thematically, and findings triangulated and integrated to give a multi-perspective account of current oversight practices in the UK. Eight TSC and six TMG meetings from eight trials were observed and audio-recorded, and 66 semi-structured interviews conducted with 52 purposively sampled key informants. Five themes are presented: (1) Collaboration within the TMG and role of the CTU; (2) Collaboration and conflict between oversight committees; (3) Priorities; (4) Communication between trial oversight groups and (5) Power and accountability. There was evidence of collaborative relationships, based on mutual respect, between CTUs, TMGs and TSCs, but also evidence of conflict. Relationships between trial oversight committees were influenced by stakeholders' priorities, both organisational and individual. Good communication following specific, recognised routes played a central role in ensuring that relationships were productive and trial oversight efficient. Participants described the possession of power over trials as a shifting political landscape, and there was lack of clarity regarding the roles and accountability of each committee, the sponsor and funder. Stakeholders' perceptions of their own power over a trial, and the power of others, influenced relationships between those involved in trial oversight. Recent

Post-marketing safety and effectiveness evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir (I): a drug use investigation.

Science.gov (United States)

Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Ariyasu, Yasuyuki; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

2014-11-01

Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. We conducted a drug use investigation of peramivir from October 2010 to February 2012 and evaluated its safety and effectiveness under routine clinical settings. We collected data of 1309 patients from 189 facilities across Japan and examined safety in 1174 patients and effectiveness in 1158 patients. In total, 143 adverse events were observed with an incidence rate of 7.33% (86/1174). Of these, 78 events were adverse drug reactions (ADRs) with an incidence rate of 4.34% (51/1174). The most frequently reported ADRs were diarrhea, vomiting, and nausea, with incidence rates of 1.87% (22/1174), 0.85% (10/1174), and 0.68% (8/1174), respectively. Moreover, no ADR was reported as serious. ADR onset was within 3 days after the start of peramivir administration in 91.0% (71 events) of the 78 ADRs, and ADRs were resolved or improved within 7 days after onset in 96.2% (75 events) of the 78 ADRs. Neither patient characteristics nor treatment factors appeared to significantly affect drug safety. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. The present study demonstrates the safety and effectiveness of peramivir under routine clinical settings. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Human rights vs. Public safety -- When can you test your workers for drugs?

Energy Technology Data Exchange (ETDEWEB)

Kossowan, B. L.

2002-06-01

Legislative and regulatory aspects of drug testing of employees vs. public safety are discussed. While in Canada federal and provincial laws concerning human rights take precedence over public safety issues, laws and regulations vary from province to province, therefore there is good reason for concern about uncertainty. To compound the uncertainty, certain relevant laws of the United States are different (generally more stringent than corresponding Canadian laws), consequently there is the possibility that certain American companies might feel justified in refusing to do business with Canadian firms that do not follow their rigid standards. The conclusion is that while the situation may be clear enough in a legal situation, it does not always work equally well in practice. Unfortunately, at the present time there is not a whole lot of guidance available for companies to manage the workplace in a practical sense.

Considerations for the nonclinical safety evaluation of antibody drug conjugates for oncology.

Science.gov (United States)

Roberts, Stanley A; Andrews, Paul A; Blanset, Diann; Flagella, Kelly M; Gorovits, Boris; Lynch, Carmel M; Martin, Pauline L; Kramer-Stickland, Kimberly; Thibault, Stephane; Warner, Garvin

2013-12-01

Antibody drug conjugates (ADCs) include monoclonal antibodies that are linked to cytotoxic small molecules. A number of these agents are currently being developed as anti-cancer agents designed to improve the therapeutic index of the cytotoxin (i.e., cytotoxic small molecule or cytotoxic agent) by specifically delivering it to tumor cells. This paper presents primary considerations for the nonclinical safety evaluation of ADCs and includes strategies for the evaluation of the entire ADC or the various individual components (i.e., antibody, linker or the cytotoxin). Considerations are presented on how to design a nonclinical safety assessment program to identify the on- and off-target toxicities to enable first-in-human (FIH) studies. Specific discussions are also included that provide details as to the need and how to conduct the studies for evaluating ADCs in genetic toxicology, tissue cross-reactivity, safety pharmacology, carcinogenicity, developmental and reproductive toxicology, biotransformation, toxicokinetic monitoring, bioanalytical assays, immunogenicity testing, test article stability and the selection of the FIH dose. Given the complexity of these molecules and our evolving understanding of their properties, there is no single all-encompassing nonclinical strategy. Instead, each ADC should be evaluated on a case-by-case scientifically-based approach that is consistent with ICH and animal research guidelines. Copyright © 2013 Elsevier Inc. All rights reserved.

The Global Fund's paradigm of oversight, monitoring, and results in Mozambique.

Science.gov (United States)

Warren, Ashley; Cordon, Roberto; Told, Michaela; de Savigny, Don; Kickbusch, Ilona; Tanner, Marcel

2017-12-12

The Global Fund is one of the largest actors in global health. In 2015 the Global Fund was credited with disbursing close to 10 % of all development assistance for health. In 2011 it began a reform process in response to internal reviews following allegations of recipients' misuse of funds. Reforms have focused on grant application processes thus far while the core structures and paradigm have remained intact. We report results of discussions with key stakeholders on the Global Fund, its paradigm of oversight, monitoring, and results in Mozambique. We conducted 38 semi-structured in-depth interviews in Maputo, Mozambique and members of the Global Fund Board and Secretariat in Switzerland. In-country stakeholders were representatives from Global Fund country structures (eg. Principle Recipient), the Ministry of Health, health or development attachés bilateral and multilateral agencies, consultants, and the NGO coordinating body. Thematic coding revealed concerns about the combination of weak country oversight with stringent and cumbersome requirements for monitoring and evaluation linked to performance-based financing. Analysis revealed that despite the changes associated with the New Funding Model, respondents in both Maputo and Geneva firmly believe challenges remain in Global Fund's structure and paradigm. The lack of a country office has many negative downstream effects including reliance on in-country partners and ineffective coordination. Due to weak managerial and absorptive capacity, more oversight is required than is afforded by country team visits. In-country partners provide much needed support for Global Fund recipients, but roles, responsibilities, and accountability must be clearly defined for a successful long-term partnership. Furthermore, decision-makers in Geneva recognize in-country coordination as vital to successful implementation, and partners welcome increased Global Fund engagement. To date, there are no institutional requirements for

75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

Science.gov (United States)

2010-09-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug Safety... and Central Nervous System Drugs Advisory Committee and the Drug Safety and Risk Management Advisory...

Pain Control in the Presence of Drug Addiction.

Science.gov (United States)

Vadivelu, Nalini; Lumermann, Leandro; Zhu, Richard; Kodumudi, Gopal; Elhassan, Amir O; Kaye, Alan David

2016-05-01

Drug addiction is present in a significant proportion of the population in the USA and worldwide. Drug addiction can occur with the abuse of many types of substances including cocaine, marijuana, stimulants, alcohol, opioids, and tranquilizers. There is a high likelihood that clinicians will encounter patients with substance abuse disorders on a regular basis with the prevalence of the use of illicit substances and the high rate of abuse of prescription drugs. The use of abuse deterrent formulations of prescription opioid agents, pill counts, and urine drug abuse screenings are all useful strategies. Optimum pain management of patients with addiction in the outpatient and inpatient setting is essential to minimize pain states. Careful selection of medications and appropriate oversight, including drug agreements, can reduce drug-induced impairments, including sleep deficits and diminished physical, social, and sexual functioning. This review, therefore, discusses the prevalence of illicit and prescription drug addiction, the challenges of achieving optimum pain control, and the therapeutic approaches to be considered in this challenging population. More research is warranted to develop improved therapies and routes of treatments for optimum pain relief and to prevent the development of central sensitization, chronic pain, and impaired physical and social functioning in patients with drug addiction.

Safety and safety analysis. From CP1 to Fukushima

International Nuclear Information System (INIS)

Yadigaroglu, George

2012-01-01

The safety of nuclear installations has been a serious concern starting from the days of infancy of this technology. When Fermi and co-workers built the first nuclear reactor in 1941, the Chicago Pile-1 or CP1 at the University of Chicago, some basic safety principles still in use today were already part of this very simple experiment. During the fast-growth period in the 1960ies, a number of NPP systems were conceived, tested and some of them built, mainly in the US and in the Soviet Union, but also in the UK, in France and in Canada, before just a handful of nuclear systems dominated: the LWRs conquered some 3 quarters of the world market and their dominance continues till today. The fission process has been amazingly well ''designed'' by nature: a remarkably simple to produce, self-sustained reaction that can be easily controlled, modulated and adjusted by a variety of available materials. Fission leads to large release of energy that can be easily collected and transformed into useful work. The process has only a major drawback, the inexorable production and accumulation in the core of the radioactive fission products that also produce decay heat. Criticality considerations put apart, the major goal of reactor safety is the confinement and cooling of these fission products. Although safety has been a major concern from the very first nuclear developments, feedback and actions following incidents and accidents have contributed to continuous enhancements. In particular, the three major nuclear accidents, TMI, Chernobyl and Fukushima had or will hopefully have in the future major impacts on safety improvements. Lessons learned from TMI have greatly enhanced the safety of LWRs, while Chernobyl triggered a number of radio-ecology studies and improved the readiness for radiological crisis management. It is hoped that Fukushima will be the trigger for much stronger international oversight and harmonization of safety practices, something that has already been launched

Safety and safety analysis. From CP1 to Fukushima

Energy Technology Data Exchange (ETDEWEB)

Yadigaroglu, George [ASCOMP GmbH, Zurich (Switzerland)

2012-02-15

The safety of nuclear installations has been a serious concern starting from the days of infancy of this technology. When Fermi and co-workers built the first nuclear reactor in 1941, the Chicago Pile-1 or CP1 at the University of Chicago, some basic safety principles still in use today were already part of this very simple experiment. During the fast-growth period in the 1960ies, a number of NPP systems were conceived, tested and some of them built, mainly in the US and in the Soviet Union, but also in the UK, in France and in Canada, before just a handful of nuclear systems dominated: the LWRs conquered some 3 quarters of the world market and their dominance continues till today. The fission process has been amazingly well ''designed'' by nature: a remarkably simple to produce, self-sustained reaction that can be easily controlled, modulated and adjusted by a variety of available materials. Fission leads to large release of energy that can be easily collected and transformed into useful work. The process has only a major drawback, the inexorable production and accumulation in the core of the radioactive fission products that also produce decay heat. Criticality considerations put apart, the major goal of reactor safety is the confinement and cooling of these fission products. Although safety has been a major concern from the very first nuclear developments, feedback and actions following incidents and accidents have contributed to continuous enhancements. In particular, the three major nuclear accidents, TMI, Chernobyl and Fukushima had or will hopefully have in the future major impacts on safety improvements. Lessons learned from TMI have greatly enhanced the safety of LWRs, while Chernobyl triggered a number of radio-ecology studies and improved the readiness for radiological crisis management. It is hoped that Fukushima will be the trigger for much stronger international oversight and harmonization of safety practices, something that has

Los Alamos National Laboratory Facilities, Security and Safeguards Division, Safeguards and Security Program Office, Protective Force Oversight Program

International Nuclear Information System (INIS)

1995-01-01

The purpose of this document is to identify and describe the duties and responsibilities of Facility Security and Safeguards (FSS) Safeguards and Security (SS) organizations (groups/offices) with oversight functions over the Protection Force (PF) subcontractor. Responsible organizations will continue their present PF oversight functions under the Cost Plus Award Fee (CPAF) assessment, but now will be required to also coordinate, integrate, and interface with other FSS S and S organizations and with the PF subcontractor to measure performance, assess Department of Energy (DOE) compliance, reduce costs, and minimize duplication of effort. The role of the PF subcontractor is to provide the Laboratory with effective and efficient protective force services. PF services include providing protection for the special nuclear material, government property and classified or sensitive information developed and/or consigned to the Laboratory, as well as protection for personnel who work or participate in laboratory activities. FSS S and S oversight of both performance and compliance standards/metrics is essential for these PF objectives to be met

More DoD Oversight Needed for Purchases Made Through the Department of Energy

Science.gov (United States)

2010-12-03

obligations or to liquidate prior valid obligations. However, expired funds are not available for new obligations nor can they be used for new requirements...Oversight Would Enable The Department of Homeland Security To Address Risks,” September 2006 GAO Report No. GAO-05-456, “Interagency Contracting Franchise

Prescription Drugs, Over-the-Counter Drugs, Supplements and Herbal Products

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... at risk? Zika virus and pregnancy Folic acid Medicine safety and pregnancy Birth defects prevention Learn how ... the-counter drugs, supplements and herbal products Prescription drugs, over-the-counter drugs, supplements and herbal products ...

Clinical Relation Extraction Toward Drug Safety Surveillance Using Electronic Health Record Narratives: Classical Learning Versus Deep Learning.

Science.gov (United States)

Munkhdalai, Tsendsuren; Liu, Feifan; Yu, Hong

2018-04-25

Medication and adverse drug event (ADE) information extracted from electronic health record (EHR) notes can be a rich resource for drug safety surveillance. Existing observational studies have mainly relied on structured EHR data to obtain ADE information; however, ADEs are often buried in the EHR narratives and not recorded in structured data. To unlock ADE-related information from EHR narratives, there is a need to extract relevant entities and identify relations among them. In this study, we focus on relation identification. This study aimed to evaluate natural language processing and machine learning approaches using the expert-annotated medical entities and relations in the context of drug safety surveillance, and investigate how different learning approaches perform under different configurations. We have manually annotated 791 EHR notes with 9 named entities (eg, medication, indication, severity, and ADEs) and 7 different types of relations (eg, medication-dosage, medication-ADE, and severity-ADE). Then, we explored 3 supervised machine learning systems for relation identification: (1) a support vector machines (SVM) system, (2) an end-to-end deep neural network system, and (3) a supervised descriptive rule induction baseline system. For the neural network system, we exploited the state-of-the-art recurrent neural network (RNN) and attention models. We report the performance by macro-averaged precision, recall, and F1-score across the relation types. Our results show that the SVM model achieved the best average F1-score of 89.1% on test data, outperforming the long short-term memory (LSTM) model with attention (F1-score of 65.72%) as well as the rule induction baseline system (F1-score of 7.47%) by a large margin. The bidirectional LSTM model with attention achieved the best performance among different RNN models. With the inclusion of additional features in the LSTM model, its performance can be boosted to an average F1-score of 77.35%. It shows that

Zero-inflated Poisson model based likelihood ratio test for drug safety signal detection.

Science.gov (United States)

Huang, Lan; Zheng, Dan; Zalkikar, Jyoti; Tiwari, Ram

2017-02-01

In recent decades, numerous methods have been developed for data mining of large drug safety databases, such as Food and Drug Administration's (FDA's) Adverse Event Reporting System, where data matrices are formed by drugs such as columns and adverse events as rows. Often, a large number of cells in these data matrices have zero cell counts and some of them are "true zeros" indicating that the drug-adverse event pairs cannot occur, and these zero counts are distinguished from the other zero counts that are modeled zero counts and simply indicate that the drug-adverse event pairs have not occurred yet or have not been reported yet. In this paper, a zero-inflated Poisson model based likelihood ratio test method is proposed to identify drug-adverse event pairs that have disproportionately high reporting rates, which are also called signals. The maximum likelihood estimates of the model parameters of zero-inflated Poisson model based likelihood ratio test are obtained using the expectation and maximization algorithm. The zero-inflated Poisson model based likelihood ratio test is also modified to handle the stratified analyses for binary and categorical covariates (e.g. gender and age) in the data. The proposed zero-inflated Poisson model based likelihood ratio test method is shown to asymptotically control the type I error and false discovery rate, and its finite sample performance for signal detection is evaluated through a simulation study. The simulation results show that the zero-inflated Poisson model based likelihood ratio test method performs similar to Poisson model based likelihood ratio test method when the estimated percentage of true zeros in the database is small. Both the zero-inflated Poisson model based likelihood ratio test and likelihood ratio test methods are applied to six selected drugs, from the 2006 to 2011 Adverse Event Reporting System database, with varying percentages of observed zero-count cells.

The impact of medicinal drugs on traffic safety: a systematic review of epidemiological studies.

Science.gov (United States)

Orriols, Ludivine; Salmi, Louis-Rachid; Philip, Pierre; Moore, Nicholas; Delorme, Bernard; Castot, Anne; Lagarde, Emmanuel

2009-08-01

To evaluate the quality of epidemiological research into effects of medicinal drugs on traffic safety and the current knowledge in this area. The bibliographic search was done in Medline electronic database using the keywords: ((accident* or crash*) and traffic and drug*) leading to 1141 references. Additional references were retrieved from the Safetylit website and the reference lists of selected studies. Original articles published in English or French, between 1 April 1979 and 31 July 2008, were considered for inclusion. We excluded descriptive studies, studies limited to alcohol or illicit drug involvement and investigations of injuries other than from traffic crashes. Studies based on laboratory tests, driving simulators or on-the-road driving tests were also excluded. Eligible studies had to evaluate the causal relationship between the use of medicinal drugs and the risk of traffic crashes. Study quality was assessed by two independent experts, according to a grid adapted from the strengthening the reporting of observational studies in epidemiology (STROBE) statement. Twenty two studies of variable methodological quality were included. Definition of drug exposure varied across studies and depended on the data sources. Potential confounding due to the interaction between the effects of the medicinal drug and disease-related symptoms was often not controlled. The risk of motor-vehicle crashes related to benzodiazepines has been amply studied and demonstrated. Results for other medicinal drugs remain controversial. There is a need for large studies, investigating the role of individual substances in the risk of road traffic crashes. Copyright 2009 John Wiley & Sons, Ltd.

Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

Directory of Open Access Journals (Sweden)

Surender Singh

2017-01-01

Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

77 FR 44256 - Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510...

Science.gov (United States)

2012-07-27

...] Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510(k... serious and sometimes fatal consequences to patients. This guidance provides recommendations to 510(k... unintended connections between enteral and nonenteral devices. This draft guidance is not final nor is it in...

Safety update regarding intranasal corticosteroids for the treatment of allergic rhinitis.

Science.gov (United States)

Blaiss, Michael S

2011-01-01

Intranasal corticosteroids (INSs) are the most efficacious medication for the treatment of allergic rhinitis. In 2006, the Joint Task Force of the American College of Allergy, Asthma, and Immunology, and the American Academy of Allergy, Asthma, and Immunology, published a white paper on the potential over-the-counter switch of INS (Bielory L, Blaiss M, Fineman SM, et al. Concerns about intranasal corticosteroids for over-the-counter use: Position statement of the Joint Task Force for the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 96:514-525, 2006). The concern of the paper was the safety of the use of these agents without oversight by a health care professional. The objective of this paper was to review published literature on the safety of INS since the publication of the task force white paper. Recent studies, which evaluated topical and systemic adverse events associated with ciclesonide (CIC), fluticasone furoate (FF), mometasone furoate (MF), triamcinolone acetonide, fluticasone propionate, budesonide, and beclomethasone dipropionate were summarized. In general, no significant topical or systemic complications were observed in these studies, although none were >1 year in duration. The newer formulations of topical corticosteroids for allergic rhinitis, such as CIC, FF, and MF, which have less systemic bioavailability, may be safer for long-term use. New studies continue to add to the reassurance of the safety of INSs in the treatment of allergic rhinitis but still do not answer the question if these agents are appropriate for long-term use without oversight by a health care professional.

78 FR 49257 - Proposed Information Collection; Comment Request; Management and Oversight of the National...

Science.gov (United States)

2013-08-13

... award. Each reserve compiles an ecological characterization or site profile to describe the biological... Collection; Comment Request; Management and Oversight of the National Estuarine Research Reserve System... estuarine research reserves representative of various regions and estuarine types in the United States to...

Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing

Directory of Open Access Journals (Sweden)

Francis A. Ortega

2018-01-01

Full Text Available Dynamic clamp, a hybrid-computational-experimental technique that has been used to elucidate ionic mechanisms underlying cardiac electrophysiology, is emerging as a promising tool in the discovery of potential anti-arrhythmic targets and in pharmacological safety testing. Through the injection of computationally simulated conductances into isolated cardiomyocytes in a real-time continuous loop, dynamic clamp has greatly expanded the capabilities of patch clamp outside traditional static voltage and current protocols. Recent applications include fine manipulation of injected artificial conductances to identify promising drug targets in the prevention of arrhythmia and the direct testing of model-based hypotheses. Furthermore, dynamic clamp has been used to enhance existing experimental models by addressing their intrinsic limitations, which increased predictive power in identifying pro-arrhythmic pharmacological compounds. Here, we review the recent advances of the dynamic clamp technique in cardiac electrophysiology with a focus on its future role in the development of safety testing and discovery of anti-arrhythmic drugs.

A Voice Crying in the Wilderness: Legislative Oversight Agencies' Efforts to Achieve Utilization

Science.gov (United States)

VanLandingham, Gary R.

2006-01-01

While legislative oversight offices, like many evaluation and policy analysis units, face substantial challenges in promoting use of their work by policymakers, they often have not taken steps to overcome these challenges by adopting the strategies suggested by the evaluation literature. Although the offices seek utilization, they have not fully…

Low hanging fruit in infectious disease drug development.

Science.gov (United States)

Kraus, Carl N

2008-10-01

Cost estimates for developing new molecular entities (NME) are reaching non-sustainable levels and coupled with increasing regulatory requirements and oversight have led many pharmaceutical sponsors to divest their anti-microbial development portfolios [Projan SJ: Why is big Pharma getting out of anti-bacterial drug discovery?Curr Opin Microbiol 2003, 6:427-430] [Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE, Jr: Trends in antimicrobial drug development: implications for the future.Clin Infect Dis 2004, 38:1279-1286]. Operational issues such as study planning and execution are significant contributors to the overall cost of drug development that can benefit from the leveraging of pre-randomization data in an evidence-based approach to protocol development, site selection and patient recruitment. For non-NME products there is even greater benefit from available data resources since these data may permit smaller and shorter study programs. There are now many available open source intelligence (OSINT) resources that are being integrated into drug development programs, permitting an evidence-based or 'operational epidemiology' approach to study planning and execution.

Current practice and perspectives in CRO oversight based on a survey performed among members of the German Association of Research-Based Pharmaceutical Companies (vfa).

Science.gov (United States)

Hennig, Michael; Hundt, Ferdinand; Busta, Susanne; Mikus, Stefan; Sanden, Per-Holger; Sörgel, Andrea; Ruppert, Thorsten

2017-01-01

In recent years, the number and scope of outsourced activities in the pharmaceutical industry have increased heavily. In addition, also the type of outsourcing has changed significantly in that time. This raises the question of whether and how sponsors retain the capability to select and to control the contract research organizations (CROs) involved and what expertise still has to be present in the development department as well as other relevant departments to ensure adequate oversight, also in line with the expectations of regulators and health authorities. In order to answer these questions, a survey was conducted among the German vfa member companies. The survey describes the latest developments and experiences in outsourcing by 18 German vfa member companies. It concentrates on measures how to implement Quality Assurance (QA) when performing outsourced clinical studies. This study shows that the majority of companies apply a full-outsourcing, preferred-provider model of clinical trial services, with the clinical research department playing the major role in this process. A large amount of guiding documents, processes and tools are used to ensure an adequate oversight of the services performed by the CRO(s). Finally the guiding principles for all oversight processes should be transparent communication, a clearly established expectation for quality, a precise definition of accountability and responsibility while avoiding silo mentality, and a comprehensive documentation of the oversight's evidence. For globally acting and outsourcing sponsors, oversight processes need to be aligned with regards to local and global perspectives. This survey shows that the current implementation of oversight processes in the participating companies covers all relevant areas to ensure highest quality and integrity of the data produced by the outsourced clinical trial.

Why does Safety Culture Matter?

International Nuclear Information System (INIS)

Dahlgren-Persson, Kerstin

2008-01-01

Dr. Kerstin Dahlgren-Persson, from the IAEA presented a plenary paper on 'Why does safety culture matter?'. The paper discussed the main conclusions of a 1998 IAEA conference on shortcomings in safety management. The conference included case studies of TVA, Cooper, Peach Bottom, Millstone, Ontario Hydro, Barsebaeck and Oskarshamn. Common symptoms included insularity; disproportionate focus on technical issues, high initial performance, lack of corporate oversight, changing management direction and cost cutting, repeat problems, and regulatory dissatisfaction. Behind these symptoms was lack of senior utility leadership with the insight, knowledge and ability to manage the unique interaction between the technology, economics, human factors and safety in a changing nuclear environment. Shortcomings relating to the regulator included lack of criteria for when regulatory actions should be taken in response to degradations in safety management, and the inability of some regulators to influence at the senior utility management level. The paper also made the following key points: - Human error is not always symptomatic of a poor safety culture. Effective root cause analysis (such as that carried out for the Columbia accident investigation) is essential to correctly differentiate between situational issues at a point in time and those rooted in organizational culture. - Leaders change culture by holding different assumptions and by making them visible through their words and action. - Regulators should consider how their regulatory strategy influences licensees. For example, a prescriptive strategy can foster a compliance based approach

Data-driven drug safety signal detection methods in pharmacovigilance using electronic primary care records: A population based study

Directory of Open Access Journals (Sweden)

Shang-Ming Zhou

2017-04-01

Data-driven analytic methods are a valuable aid to signal detection of ADEs from large electronic health records for drug safety monitoring. This study finds the methods can detect known ADE and so could potentially be used to detect unknown ADE.

[HERA-QUEST: HTA evaluation of generic pharmaceutical products to improve quality, economic efficiency, patient safety and transparency in drug product changes in hospitals].

Science.gov (United States)

Gyalrong-Steur, Miriam; Kellermann, Anita; Bernard, Rudolf; Berndt, Georg; Bindemann, Meike; Nusser-Rothermundt, Elfriede; Amann, Steffen; Brakebusch, Myga; Brüggmann, Jörg; Tydecks, Eva; Müller, Markus; Dörje, Frank; Kochs, Eberhard; Riedel, Rainer

2017-04-01

In view of the rising cost pressure and an increasing number of drug shortages, switches between generic drug preparations have become a daily routine in hospitals. To ensure consistently high treatment quality and best possible patient safety, the equivalence of the new and the previous drug preparation must be ensured before any change in the purchase of pharmaceutical products takes place. So far, no easily usable, transparent and standardized instrument for this kind of comparison between generic drug products has been available. A group of pharmaceutical experts has developed the drug HTA (health technology assessment) model "HERA" (HTA Evaluation of geneRic phArmaceutical products) through a multi-step process. The instrument is designed to perform both a qualitative and economic comparison of equivalent drug preparations ("aut idem" substitution) before switching products. The economic evaluation does not only consider unit prices and consumption quantity, but also the processing costs associated with a product change process. The qualitative comparison is based on the evaluation of 34 quality criteria belonging to six evaluation fields (e.g., approval status, practical handling, packaging design). The objective evaluation of the quality criteria is complemented by an assessment of special features of the individual hospital for complex drug switches, including the feedback of the physicians utilizing the drug preparation. Thus potentially problematic switches of pharmaceutical products can be avoided at the best possible rate, contributing to the improvement of patient safety. The novel drug HTA model HERA is a tool used in clinical practice that can add to an increase in quality, therapeutic safety and transparency of drug use while simultaneously contributing to the economic optimization of drug procurement in hospitals. Combining these two is essential for hospitals facing the tension between rising cost pressure and at the same time increasing demands

Industry Presentation to Regulatory Workshop

International Nuclear Information System (INIS)

Treasure, Mark

2012-01-01

Mr. Mark Treasure from EDF NGL gave a presentation on industry perspectives on safety culture oversight. Mr. Treasure is the Nuclear Inspection and Oversight Manager within the Safety and Regulation Division. The presentation started with an explanation of the role of the nuclear inspection and oversight group (internal regulator), and their current approach to internal oversight of safety culture. A key element of the current internal regulatory oversight program is Management and Leadership Assessments. These are carried out by a team including management peers from other plants to enhance credibility. Findings can be linked to safety performance, and typically identify issues in areas such as accountability arrangements and strategic focus of the leadership team. Safety indicators have also been introduced to show trends in safety management and safety performance for each EDF UK nuclear power plant. A periodic nuclear safety culture survey is also carried out to identify focus areas and progress. The presentation included discussion on views of the role of the nuclear regulator. Important aspects were identified as: - Supporting the internal regulator by seeking to understand before taking enforcement action, maintaining an open dialogue and recognising that this area is complex and that there is rarely a 'silver bullet' solution. - Communication: being visible and actively discussing safety improvement, and use of language which emphasises nuclear safety rather than legal compliance. - Positive reinforcement to recognise efforts and encourage further improvement

75 FR 78779 - Order Approving Public Company Accounting Oversight Board Supplemental Budget Request To...

Science.gov (United States)

2010-12-16

...; Securities Exchange Act of 1934 Release No. 63526/December 10, 2010] Order Approving Public Company... Company Accounting Oversight Board (the ``PCAOB'') to oversee the audits of companies and related matters..., subject to approval by the Commission, auditing and related attestation, quality control, ethics, and...

The development of safety cases for healthcare services: Practical experiences, opportunities and challenges

International Nuclear Information System (INIS)

Sujan, Mark; Spurgeon, Peter; Cooke, Matthew; Weale, Andy; Debenham, Philip; Cross, Steve

2015-01-01

There has been growing interest in the concept of safety cases for medical devices and health information technology, but questions remain about how safety cases can be developed and used meaningfully in the safety management of healthcare services and processes. The paper presents two examples of the development and use of safety cases at a service level in healthcare. These first practical experiences at the service level suggest that safety cases might be a useful tool to support service improvement and communication of safety in healthcare. The paper argues that safety cases might be helpful in supporting healthcare organisations with the adoption of proactive and rigorous safety management practices. However, it is also important to consider the different level of maturity of safety management and regulatory oversight in healthcare. Adaptations to the purpose and use of safety cases might be required, complemented by the provision of education to both practitioners and regulators. - Highlights: • Empirical description of safety case development at service level in healthcare. • Safety cases can support adoption of proactive and rigorous safety management. • Adaptation to purpose and use of safety cases might be required in healthcare. • Education should be provided to practitioners and regulators

A Cost Analysis of Hospitalizations for Infections Related to Injection Drug Use at a County Safety-Net Hospital in Miami, Florida

OpenAIRE

Tookes, Hansel; Diaz, Chanelle; Li, Hua; Khalid, Rafi; Doblecki-Lewis, Susanne

2015-01-01

Background Infections related to injection drug use are common. Harm reduction strategies such as syringe exchange programs and skin care clinics aim to prevent these infections in injection drug users (IDUs). Syringe exchange programs are currently prohibited by law in Florida. The goal of this study was to estimate the mortality and cost of injection drug use-related bacterial infections over a 12-month period to the county safety-net hospital in Miami, Florida. Additionally, the prevalence...

20 CFR 411.595 - What oversight procedures are planned for the EN payment systems?

Science.gov (United States)

2010-04-01

... EN payment systems? 411.595 Section 411.595 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.595 What oversight procedures are planned for the EN payment systems? We use audits, reviews, studies and observation of daily...

Regulatory oversight report 2015 concerning nuclear safety in Swiss nuclear installations

International Nuclear Information System (INIS)

2016-06-01

The Swiss Federal Nuclear Safety Inspectorate (ENSI) assesses and monitors nuclear facilities in Switzerland. These include the five nuclear power plants (Beznau Units 1 and 2, Muehleberg, Goesgen and Leibstadt), the interim storage facilities based at each plant, the Central Interim Storage Facility (Zwilag) at Wuerenlingen together with the nuclear facilities at the Paul Scherrer Institute (PSI), the University of Basel and the Federal Institute of Technology in Lausanne (EPFL), as well as the transport of radioactive materials and the preparatory work for a deep geological repository for nuclear waste. Using a combination of inspections, regulatory meetings, examinations and analyses together with reports from the licensees of individual facilities, ENSI obtains the required overview of nuclear safety in these facilities. ENSI maintains its own emergency organization. It provides the public with information on particular events and findings in nuclear facilities. ENSI publishes an annual Radiological Protection Report and a Research and Experience Report. Chapters 1 to 4 of this Surveillance Report deal with operational experience, systems technology, radiological protection and management of the 5 Swiss nuclear power plants. Chapter 5 deals with Zwilag. Chapters 6 and 7 are devoted to the nuclear facilities at PSI and the research reactor at EPFL as well as the decommissioned University of Basel’s research reactor. Chapter 8 covers the transport of radioactive materials. The subject of Chapter 9 is the deep geological storage of radioactive waste including work within the framework of the Sectoral Plan. Finally, Chapter 10 deals with generic issues relevant to all facilities such as probabilistic safety analyses. In 2015, all five nuclear power plants in Switzerland were safely operated and ENSI concluded that each had adhered to its approved operating conditions. There were 34 reportable events at the nuclear power plants; 32 events were rated at Level 0 on

76 FR 10135 - Public Housing Evaluation and Oversight: Changes to the Public Housing Assessment System (PHAS...

Science.gov (United States)

2011-02-23

... Vol. 76 Wednesday, No. 36 February 23, 2011 Part III Department of Housing and Urban Development 24 CFR Parts 901, 902, and 907 Public Housing Evaluation and Oversight: Changes to the Public Housing...

Chemistry Programme for Water Cooled Nuclear Power Plants. Specific Safety Guide

Energy Technology Data Exchange (ETDEWEB)

NONE

2011-01-15

This publication provides guidance on establishing a high standard chemistry programme in accordance with plant safety policy and regulatory requirements. It will be useful to managers of operating organizations and other staff responsible for supporting or monitoring plant activities and for oversight of the plant chemistry programme, as well as to regulatory bodies. Contents: 1. Introduction; 2. Functions, responsibilities and interfaces; 3. Chemistry programme; 4. Chemistry control; 5. Chemistry aspects of radiation exposure optimization; 6. Chemistry surveillance; 7. Management of chemistry data; 8. Training and qualification; 9. Quality control of chemicals and other substances.

Chemistry Programme for Water Cooled Nuclear Power Plants. Specific Safety Guide

International Nuclear Information System (INIS)

2011-01-01

This publication provides guidance on establishing a high standard chemistry programme in accordance with plant safety policy and regulatory requirements. It will be useful to managers of operating organizations and other staff responsible for supporting or monitoring plant activities and for oversight of the plant chemistry programme, as well as to regulatory bodies. Contents: 1. Introduction; 2. Functions, responsibilities and interfaces; 3. Chemistry programme; 4. Chemistry control; 5. Chemistry aspects of radiation exposure optimization; 6. Chemistry surveillance; 7. Management of chemistry data; 8. Training and qualification; 9. Quality control of chemicals and other substances

Nonclinical safety biomarkers of drug-induced vascular injury: current status and blueprint for the future.

Science.gov (United States)

Mikaelian, Igor; Cameron, Mark; Dalmas, Deidre A; Enerson, Bradley E; Gonzalez, Raymond J; Guionaud, Silvia; Hoffmann, Peter K; King, Nicholas M P; Lawton, Michael P; Scicchitano, Marshall S; Smith, Holly W; Thomas, Roberta A; Weaver, James L; Zabka, Tanja S

2014-06-01

Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium (PSTC), a precompetitive collaboration of pharmaceutical companies and the U.S. Food and Drug Administration (FDA), formed the Vascular Injury Working Group (VIWG) to develop and qualify translatable biomarkers of DIVI. The VIWG focused its research on acute DIVI because early detection for clinical and nonclinical safety monitoring is desirable. The VIWG developed a strategy based on the premise that biomarkers of DIVI in rat would be translatable to humans due to the morphologic similarity of vascular injury between species regardless of mechanism. The histomorphologic lexicon for DIVI in rat defines degenerative and adaptive findings of the vascular endothelium and smooth muscles, and characterizes inflammatory components. We describe the mechanisms of these changes and their associations with candidate biomarkers for which advanced analytical method validation was completed. Further development is recommended for circulating microRNAs, endothelial microparticles, and imaging techniques. Recommendations for sample collection and processing, analytical methods, and confirmation of target localization using immunohistochemistry and in situ hybridization are described. The methods described are anticipated to aid in the identification and qualification of translational biomarkers for DIVI. © 2014 by The Author(s).

The Use of Social Media in Orphan Drug Development.

Science.gov (United States)

Milne, Christopher-Paul; Ni, Wendi

2017-11-01

Social media has transformed how people interact with one another through the Internet, and it has the potential to do the same for orphan drug development. Currently, social media influences the orphan drug development process in the following three ways: assisting the study of orphan diseases, increasing the awareness of orphan disease, and playing a vital role in clinical trials. However, there are some caveats to the utilization of social media, such as the need to protect patient privacy by adequately de-identifying personal health information, assuring consistent quality and representativeness of the data, and preventing the unblinding of patient group assignments. Social media has both potential for improving orphan drug development and pitfalls, but with proper oversight on the part of companies, support and participation of patients and their advocacy groups, and timely guidance from regulatory authorities, the positives outweigh the negatives for this powerful and patient-centric tool. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Control, oversight and related terms in the international guidance on geological disposal of radioactive waste - Review of definitions and use

International Nuclear Information System (INIS)

2014-01-01

This document presents the most complete analysis of the use of the words control, oversight, etc. as used in NEA, IAEA and ICRP literature connected to radioactive waste disposal. It reveals the many different ways the same word, 'control', has been used in international guidance and ambiguities than can arise, especially so for the post-closure phase of the repository. The newly introduced ICRP terminology, namely the use of the words 'oversight' and 'built-in controls', represents a step forward in terminology and resolves the ambiguity

Probabilistic assessment methods as a tool for developing nations to make safety decisions

International Nuclear Information System (INIS)

Gumley, P.; Inamdar, S.V.

1985-01-01

This paper advocates the use of probabilistic safety assessment methods in making safety decisions. It discusses the question of adequate safety - what it means to a country buying a nuclear power plant, and how probabilistic safety assessment studies of the reference plant can be used for ensuring this adequate safety. It is proposed that adequate safety means ensuring that the plant would behave, in accident conditions, in a manner similar to the way it is expected to behave were it in the country of origin. For this one needs to know how the plant responds under somewhat altered conditions. These altered conditions can arise from such factors as varying reliability of electrical grids, different manufacturing technology, local systems design and operator capability. In the design of nuclear power plants, the traditional approach to safety has led to the belief that availability and effectiveness of safety systems alone are all that is required to ensure plant safety. This belief can result in design oversights leading to potential problems arising from the power production systems and the service systems. Participation by the buying country in the design of such systems, and understanding the safety implications thereof, can be facilitated by probabilistic safety assessment methods. This philosophy is illustrated in this paper by examples. (author)

75 FR 81684 - Order Approving Public Company Accounting Oversight Board Budget and Annual Accounting Support...

Science.gov (United States)

2010-12-28

... Accounting Oversight Board Budget and Annual Accounting Support Fee for Calendar Year 2011 The Sarbanes-Oxley Act of 2002, as amended (the ``Sarbanes-Oxley Act''), established the Public Company Accounting... through registration of public accounting firms and standard setting, inspection, and disciplinary...

78 FR 11915 - Order Approving Public Company Accounting Oversight Board Budget and Annual Accounting Support...

Science.gov (United States)

2013-02-20

... Accounting Oversight Board Budget and Annual Accounting Support Fee for Calendar Year 2013 The Sarbanes-Oxley Act of 2002, as amended (the ``Sarbanes-Oxley Act''),\\1\\ established the Public Company Accounting... through registration of public accounting firms and standard setting, inspection, and disciplinary...

77 FR 2576 - Order Approving Public Company Accounting Oversight Board Budget and Annual Accounting Support...

Science.gov (United States)

2012-01-18

... Accounting Oversight Board Budget and Annual Accounting Support Fee for Calendar Year 2012 The Sarbanes-Oxley Act of 2002, as amended (the ``Sarbanes-Oxley Act''),\\1\\ established the Public Company Accounting... through registration of public accounting firms and standard setting, inspection, and disciplinary...

The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity

International Nuclear Information System (INIS)

Amacher, David E.

2010-01-01

Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in