76 FR 78059 - Self-Regulatory Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change...

Science.gov (United States)

2011-12-15

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65927; File No. SR-OCC-2011-15] Self-Regulatory Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change Relating to Management of..., future regulatory requirements for clearinghouses could impose liquidity requirements that would be...

78 FR 28267 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

Science.gov (United States)

2013-05-14

... Trust Company (``DTC'') and maintain accounts to facilitate Delivery Orders (``DOs'') to approved... Commission to approve a proposed rule change of a self-regulatory organization if it finds that such proposed... securities transactions and foster cooperation and coordination with persons engaged in the clearance and...

75 FR 1437 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a...

Science.gov (United States)

2010-01-11

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61274; File No. SR-CBOE-2009-089] Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a Proposed Rule... announce to members via Regulatory Circular any determination regarding the routing of market stock-option...

77 FR 27529 - Self-Regulatory Organizations; ICE Clear Credit LLC; Order Granting Accelerated Approval of...

Science.gov (United States)

2012-05-10

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66922; File No. SR-ICC-2012-05] Self-Regulatory... Commission to approve a proposed rule change of a self-regulatory organization if it finds that such proposed... of the Comptroller of the Currency, U.K. Financial Services Authority, or any other regulatory body...

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

Science.gov (United States)

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

2011-03-01

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

77 FR 76319 - Self-Regulatory Organizations; BOX Options Exchange LLC; Order Approving Minor Rule Violation...

Science.gov (United States)

2012-12-27

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68489; File No. 4-655] Self-Regulatory Organizations; BOX Options Exchange LLC; Order Approving Minor Rule Violation Plan for BOX Options Exchange LLC... \\4\\ requiring that a self-regulatory organization (``SRO'') promptly file notice with the Commission...

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

International Nuclear Information System (INIS)

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

1995-01-01

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

77 FR 40928 - Self-Regulatory Organizations; C2 Options Exchange, Incorporated; Order Granting Approval of...

Science.gov (United States)

2012-07-11

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67357; File No. SR-C2-2012-011] Self-Regulatory Organizations; C2 Options Exchange, Incorporated; Order Granting Approval of Proposed Rule Change To Implement a... and subsequently migrates to the DRF, the regulatory data for the portion of the day that the main...

77 FR 52096 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Order Approving a Proposed Rule Change, as...

Science.gov (United States)

2012-08-28

...'s rules, the financial and regulatory risk management controls and supervisory procedures required...-Regulatory Organizations; EDGX Exchange, Inc.; Order Approving a Proposed Rule Change, as Modified by... that broker-dealers appropriately control the risks associated with market access, so as not to...

75 FR 2899 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving Proposed Rule Change...

Science.gov (United States)

2010-01-19

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61333; File No. SR-NYSE-2009-117] Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving Proposed Rule Change Amending Its... regulatory program. III. Discussion and Commission's Findings After careful review, the Commission finds that...

Innovating by developing new uses of already-approved drugs: trends in the marketing approval of supplemental indications.

Science.gov (United States)

DiMasi, Joseph A

2013-06-01

Much of the literature on trends and factors affecting biopharmaceutical innovation has focused overwhelmingly on the development and approval of never-before approved drugs and biologics. Little attention has been paid to new uses for already-approved compounds, which can be an important form of innovation. This paper aimed to determine and analyze recent trends in the number and type of new or modified US indication approvals for drugs and biologics. We also examine regulatory approval-phase times for new-use efficacy supplements and compare them to approval-phase times for original-use approvals over the same period. We developed a data set of efficacy supplements approved by the US Food and Drug Administration (FDA) from 1998 to 2011 that includes information on the type, approval-phase time (time from submission to the FDA of an application for marketing approval to approval of the application), and FDA therapeutic-significance rating for the approved application, which we obtained from an FDA Web site. This data set was merged with a Tufts Center for the Study of Drug Development (CSDD) data set of US new drug and biologics approvals. We developed descriptive statistics on trends in the number and type of new-use efficacy supplements, on US regulatory approval-phase times for the supplements, and on original new drug and biologics approvals over the study period and for the time from original- to new-use approval. The total number of new-use efficacy-supplement approvals did not exhibit a marked trend, but the number of new pediatric-indication approvals increased substantially. Approval-phase times for new-use supplements varied by therapeutic class and FDA therapeutic-significance rating. Mean approval-phase times were highest for central nervous system compounds (13.8 months) and lowest for antineoplastics (8.9 months). The mean time from original to supplement approval was substantially longer for new pediatric indications than for other new uses. Mean

77 FR 52097 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Order Approving a Proposed Rule Change, as...

Science.gov (United States)

2012-08-28

... financial and regulatory risk management controls and supervisory procedures required by Rule 15c3-5 under...-Regulatory Organizations; EDGA Exchange, Inc.; Order Approving a Proposed Rule Change, as Modified by... that broker-dealers appropriately control the risks associated with market access, so as not to...

76 FR 2737 - Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed...

Science.gov (United States)

2011-01-14

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63668; File No. SR-NSCC-2010-09] Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed Rule Change... Facility January 6, 2011. I. Introduction On August 30, 2010, the National Securities Clearing Corporation...

77 FR 66196 - Self-Regulatory Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change...

Science.gov (United States)

2012-11-02

... Accounting Principles (``GAAP''). Canadian clearing members that use Form 1 report the same, and in some... Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change Relating to Financial... financial reporting by Canadian clearing members to reflect the Investment Industry Regulatory Organization...

Companion diagnostics: a regulatory perspective from the last 5 years of molecular companion diagnostic approvals.

Science.gov (United States)

Roscoe, Donna M; Hu, Yun-Fu; Philip, Reena

2015-01-01

Companion diagnostics are essential for the safe and effective use of the corresponding therapeutic products. The US FDA has approved a number of companion diagnostics used to select cancer patients for treatment with contemporaneously approved novel therapeutics. The processes of co-development and co-approval of a therapeutic product and its companion diagnostic have been a learning experience that continues to evolve. Using several companion diagnostics as examples, this article describes the challenges associated with the scientific, clinical and regulatory hurdles faced by FDA and industry alike. Taken together, this discussion is intended to assist manufacturers toward a successful companion diagnostics development plan.

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

Science.gov (United States)

2010-01-19

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

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

Science.gov (United States)

2012-01-31

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

Regulatory Challenges for Cartilage Repair Technologies.

Science.gov (United States)

McGowan, Kevin B; Stiegman, Glenn

2013-01-01

In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible.

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

Science.gov (United States)

2011-10-19

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

GMOs in animal agriculture: time to consider both costs and benefits in regulatory evaluations.

Science.gov (United States)

Van Eenennaam, Alison L

2013-09-25

In 2012, genetically engineered (GE) crops were grown by 17.3 million farmers on over 170 million hectares. Over 70% of harvested GE biomass is fed to food producing animals, making them the major consumers of GE crops for the past 15 plus years. Prior to commercialization, GE crops go through an extensive regulatory evaluation. Over one hundred regulatory submissions have shown compositional equivalence, and comparable levels of safety, between GE crops and their conventional counterparts. One component of regulatory compliance is whole GE food/feed animal feeding studies. Both regulatory studies and independent peer-reviewed studies have shown that GE crops can be safely used in animal feed, and rDNA fragments have never been detected in products (e.g. milk, meat, eggs) derived from animals that consumed GE feed. Despite the fact that the scientific weight of evidence from these hundreds of studies have not revealed unique risks associated with GE feed, some groups are calling for more animal feeding studies, including long-term rodent studies and studies in target livestock species for the approval of GE crops. It is an opportune time to review the results of such studies as have been done to date to evaluate the value of the additional information obtained. Requiring long-term and target animal feeding studies would sharply increase regulatory compliance costs and prolong the regulatory process associated with the commercialization of GE crops. Such costs may impede the development of feed crops with enhanced nutritional characteristics and durability, particularly in the local varieties in small and poor developing countries. More generally it is time for regulatory evaluations to more explicitly consider both the reasonable and unique risks and benefits associated with the use of both GE plants and animals in agricultural systems, and weigh them against those associated with existing systems, and those of regulatory inaction. This would represent a shift away

77 FR 15432 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

Science.gov (United States)

2012-03-15

... corporate governance structure of OCC by: (i) Increasing the number of public directors on OCC's Board of... directs the Commission to approve a proposed rule change of a self-regulatory organization if it finds... Directors, OCC stated that the changes would enhance the corporate governance structure at OCC. As such, the...

77 FR 4844 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a...

Science.gov (United States)

2012-01-31

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66235; File No. SR-CBOE-2011-114] Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a Proposed Rule Change Relating to Complex Order Processing in Hybrid 3.0 Classes January 25, 2012. I. Introduction On November 29, 2011, the Chicago Board Options...

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

Science.gov (United States)

Benda, Norbert; Brandt, Andreas

2018-01-01

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

77 FR 4605 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Order Granting Approval of Proposed Rule...

Science.gov (United States)

2012-01-30

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66231; File No. SR-EDGA-2011-40] Self-Regulatory Organizations; EDGA Exchange, Inc.; Order Granting Approval of Proposed Rule Change Amending EDGA Rule 11.9 January 24, 2012. On December 2, 2011, EDGA Exchange, Inc. (``Exchange'' or ``EDGA'') filed...

75 FR 30095 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Approving Proposed Rule Amending Its...

Science.gov (United States)

2010-05-28

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62157; File No. SR-NYSEArca-2010-28] Self-Regulatory Organizations; NYSE Arca, Inc.; Order Approving Proposed Rule Amending Its Schedule of Fees May 24, 2010. On April 12, 2010, NYSE Arca, Inc. (``NYSE Arca'') filed with the Securities and Exchange...

78 FR 62814 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

Science.gov (United States)

2013-10-22

...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change To Assume... Authority and Supervision September 30, 2013. On July 31, 2013, The NASDAQ Stock Market LLC (``NASDAQ'' or...) Manipulation patterns that monitor solely NASDAQ activity, including patterns that monitor the Exchange's...

77 FR 65237 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed...

Science.gov (United States)

2012-10-25

...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed Rule Change...Tree Trust October 19, 2012. I. Introduction On August 15, 2012, The NASDAQ Stock Market LLC (``Nasdaq... temporary defensive strategies that are inconsistent with its investment strategies, the Fund's ability to...

Securing classification and regulatory approval for deepwater projects: management challenges in a global environment

Energy Technology Data Exchange (ETDEWEB)

Feijo, Luiz P.; Burton, Gareth C. [American Bureau of Shipping (ABS), Rio de Janeiro, RJ (Brazil)

2008-07-01

As the offshore industry continues to develop and move into increasingly deeper waters, technological boundaries are being pushed to new limits. Along with these advances, the design, fabrication and installation of deepwater oil and gas projects has become an increasingly global endeavor. After providing an overview of the history and role of Classification Societies, this paper reviews the challenges of securing classification and regulatory approval in a global environment. Operational, procedural and technological changes which one Classification Society; the American Bureau of Shipping, known as ABS, has implemented to address these challenges are presented. The result of the changes has been a more customized service aiming at faster and more streamlined classification approval process. (author)

77 FR 48570 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

Science.gov (United States)

2012-08-14

... Underlying Securities) of the NASDAQ Options Market rules.\\11\\ Additionally, the Target Component's and the...\\ Additionally, the Target Component's and the Benchmark Component's trading volume (in all markets in which the...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change Relating to the...

76 FR 55148 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change To Adopt...

Science.gov (United States)

2011-09-06

...-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change To Adopt Rules for the...-4 thereunder,\\2\\ a proposed rule change to adopt rules for the qualification, listing, and delisting... the Proposal The Exchange proposes rules to adopt a program for the qualification, listing, and...

76 FR 4968 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change...

Science.gov (United States)

2011-01-27

...-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change Relating to Listing and Trading Shares of the AdvisorShares Active Bear ETF January 19, 2011. I. Introduction On... of the security or investment in the portfolio. \\14\\ Under accounting procedures followed by the Fund...

78 FR 75437 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

Science.gov (United States)

2013-12-11

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-71004; File No. SR-Phlx-2013-101] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule Change Regarding the Short Term Options Program December 6, 2013. I. Introduction On October 3, 2013, NASDAQ OMX PHLX LLC...

77 FR 67851 - Self-Regulatory Organizations; BOX Options Exchange LLC; Order Approving Proposed Rule Change To...

Science.gov (United States)

2012-11-14

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68177; File No. SR-BOX-2012-003] Self-Regulatory Organizations; BOX Options Exchange LLC; Order Approving Proposed Rule Change To Amend the Price Improvement Period November 7, 2012. I. Introduction On July 25, 2012, BOX Options Exchange LLC (``Exchange...

76 FR 8793 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

Science.gov (United States)

2011-02-15

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63875; File No. SR-Phlx-2010-183] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule Change Expanding Its Short Term Option Program February 9, 2011. I. Introduction On December 15, 2010, NASDAQ OMX PHLX LLC...

75 FR 69491 - Self-Regulatory Organizations; Order Approving Proposed Rule Change by New York Stock Exchange...

Science.gov (United States)

2010-11-12

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63266; File No. SR-NYSE-2010-67] Self-Regulatory Organizations; Order Approving Proposed Rule Change by New York Stock Exchange LLC Changing the NYBX Order Execution Sequence November 5, 2010. I. Introduction On September 9, 2010, the New York...

75 FR 9988 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Granting Approval of Proposed Rule...

Science.gov (United States)

2010-03-04

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61590; File No. SR-Phlx-2009-113] Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Granting Approval of Proposed Rule Change Relating to Index Option Position Limits February 25, 2010. On December 29, 2009, NASDAQ OMX PHLX, Inc. (``Phlx'' or...

76 FR 2182 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

Science.gov (United States)

2011-01-12

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63654; File No. SR-Phlx-2010-158] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule Change Establishing a $5 Strike Price Program January 6, 2011. I. Introduction On November 12, 2010, NASDAQ OMX PHLX LLC...

78 FR 15394 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving Proposed Rule Change...

Science.gov (United States)

2013-03-11

...-Regulatory Organizations; New York Stock Exchange LLC; Order Approving Proposed Rule Change Adopting... paragraph (d) it contains a provision establishing how the transition period from NYSE Rule 477 will work... to announce the effective date of the new rules at least 30 days in advance in an Information...

76 FR 45308 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed...

Science.gov (United States)

2011-07-28

...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed Rule Change To... change should provide NOM Participants assistance in effectively managing their quotations. \\6\\ 15 U.S.C...,\\2\\ a proposed rule change to adopt a new risk monitor mechanism. The proposed rule change was...

77 FR 49034 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

Science.gov (United States)

2012-08-15

... entering new orders at inferior prices. This occurs because the current process directs the order to NASDAQ...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change To Amend Rule... June 14, 2012, The NASDAQ Stock Market LLC (``NASDAQ'' or ``Exchange''), filed with the Securities and...

78 FR 62834 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed...

Science.gov (United States)

2013-10-22

... Fund of First Trust Exchange-Traded Fund VII October 9, 2013. I. Introduction On August 16, 2013, The... for the provision of custody, transfer agency, and accounting agent services with the same or with...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed Rule Change...

76 FR 21085 - Self-Regulatory Organizations; NASDAQ Stock Market, LLC; Order Approving Proposed Rule Change To...

Science.gov (United States)

2011-04-14

...-Regulatory Organizations; NASDAQ Stock Market, LLC; Order Approving Proposed Rule Change To Amend The NASDAQ OMX Group, Inc. By- Laws April 8, 2011. I. Introduction On February 8, 2011, The NASDAQ Stock Market... vote cast either ``for'' or ``against'' that director's election. In its filing, NASDAQ noted that...

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

Science.gov (United States)

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

2014-12-01

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

77 FR 47472 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving Proposed Rule Change...

Science.gov (United States)

2012-08-08

... proposed rule change to make certain amendments that, in part, clarified the operation of the new Market... equitable principles of trade, to remove impediments to and perfect the mechanism of a free and open market...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving Proposed Rule Change, as Modified by...

77 FR 35455 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Granting Approval of Proposed...

Science.gov (United States)

2012-06-13

...-Regulatory Organizations; New York Stock Exchange LLC; Order Granting Approval of Proposed Rule Change Amending NYSE Rule 107B To Add a Class of Supplemental Liquidity Providers That Are Registered as Market... proposed rule change to amend NYSE Rule 107B to add a class of Supplemental Liquidity Providers (``SLP...

75 FR 12590 - Self-Regulatory Organizations; The Chicago Stock Exchange, Inc.; Order Approving a Proposed Rule...

Science.gov (United States)

2010-03-16

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61680; File No. SR-CHX-2009-18] Self-Regulatory Organizations; The Chicago Stock Exchange, Inc.; Order Approving a Proposed Rule Change To Amend Its Co-Location Fees March 10, 2010. I. Introduction On December 22, 2009, the Chicago Stock Exchange, Inc. (``CHX'' or...

77 FR 38879 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change...

Science.gov (United States)

2012-06-29

... marketable non-displayed interest, the Market Maker would be required to re-enter a quotation for purposes of...-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change Adding New... Securities Exchange Act of 1934 (``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ a proposed rule change to add new...

76 FR 67238 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change by BATS...

Science.gov (United States)

2011-10-31

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65619, File No. SR-BATS-2011-032] Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change by BATS Exchange, Inc. To Adopt Rules Applicable to Auctions Conducted by the Exchange for Exchange-Listed Securities October 25, 2011. I. Introduction On August 22, 2011,...

75 FR 1438 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving a Proposed Rule...

Science.gov (United States)

2010-01-11

...)(iv). Finally, because DMMs no longer act as agent for orders on the Display Book under the rules of... the Policy would not be in violation the Order Display rule \\8\\ and/or the Firm Quote rule \\9\\ under...-Regulatory Organizations; New York Stock Exchange LLC; Order Approving a Proposed Rule Change Rescinding...

75 FR 1439 - Self-Regulatory Organizations; NYSE Amex LLC; Order Approving a Proposed Rule Change Rescinding...

Science.gov (United States)

2010-01-11

...(a)(iv). Finally, because DMMs no longer act as agent for orders on the Display Book under the rules... fails to follow the Policy would not be in violation the Order Display rule \\8\\ and/or the Firm Quote...-Regulatory Organizations; NYSE Amex LLC; Order Approving a Proposed Rule Change Rescinding NYSE Information...

75 FR 80553 - Self-Regulatory Organizations; NYSE Amex LLC; Order Approving a Proposed Rule Change Relating to...

Science.gov (United States)

2010-12-22

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63558; File No. SR-NYSEAmex-2010-100] Self-Regulatory Organizations; NYSE Amex LLC; Order Approving a Proposed Rule Change Relating to Complex Orders December 16, 2010. I. Introduction On October 20, 2010, NYSE Amex LLC (``NYSE Amex'' or the ``Exchange...

75 FR 65541 - Self-Regulatory Organizations; Order Approving Proposed Rule Change by NASDAQ OMX PHLX, Inc. To...

Science.gov (United States)

2010-10-25

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63132; File No. SR-Phlx-2010-118] Self-Regulatory Organizations; Order Approving Proposed Rule Change by NASDAQ OMX PHLX, Inc. To Expand the $.50 Strike Price Program October 19, 2010. On August 25, 2010, NASDAQ OMX PHLX, Inc. (``Phlx'' or ``Exchange...

75 FR 38584 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Approving a Proposed Rule Change To...

Science.gov (United States)

2010-07-02

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62395; File No. SR-Phlx-2010-18] Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Approving a Proposed Rule Change To Codify Prices for Co-Location Services June 28, 2010. I. Introduction On January 29, 2010, NASDAQ OMX PHLX (``Phlx'' or...

75 FR 38585 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change To...

Science.gov (United States)

2010-07-02

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62396; File No. SR-BX-2010-012] Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change To Codify Prices for Co-Location Services June 28, 2010. I. Introduction On January 29, 2010, NASDAQ OMX BX, Inc. (``BX'' or ``Exchange...

What's the Regulatory Value of a Target Product Profile?

Science.gov (United States)

Breder, Christopher D; Du, Wenny; Tyndall, Adria

2017-07-01

Target product profiles (TPPs) are used as a regulatory tool for dialog on clinical development or manufacturing plans. Drugs and biologics approved by the FDA that mention TPPs are associated with more efficient regulatory review times, perhaps as a result of increased planning or because the TPP promotes well-organized regulatory dialog. Published by Elsevier Ltd.

76 FR 21932 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

Science.gov (United States)

2011-04-19

... statement therein, as follows: I. Introduction On February 4, 2011, the Financial Industry Regulatory...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting Approval of a... Financial Industry Regulatory Authority, Inc. (``FINRA'') to amend Rule 13806 of the Code of Arbitration...

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

Science.gov (United States)

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

2017-01-01

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

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

Directory of Open Access Journals (Sweden)

J. Javier Hernandez

2017-11-01

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

Regulatory practices of radiation safety of SNF transportation in Russia

International Nuclear Information System (INIS)

Kuryndina, Lidia; Kuryndin, Anton; Stroganov, Anatoly

2008-01-01

This paper overviews current regulatory practices for the assurance of nuclear and radiation safety during railway transportation of SNF on the territory of Russian Federation from NPPs to longterm-storage of reprocessing sites. The legal and regulatory requirements (mostly compliant with IAEA ST-1), licensing procedure for NM transportation are discussed. The current procedure does not require a regulatory approval for each particular shipment if the SNF fully comply with the Rosatom's branch standard and is transported in approved casks. It has been demonstrated that SNF packages compliant with the branch standard, which is knowingly provide sufficient safety margin, will conform to the federal level regulations. The regulatory approval is required if a particular shipment does not comply with the branch standard. In this case, the shipment can be approved only after regulatory review of Applicant's documents to demonstrate that the shipment still conformant to the higher level (federal) regulations. The regulatory review frequently needs a full calculation test of the radiation safety assurance. This test can take a lot of time. That's why the special calculation tools were created in SEC NRS. These tools aimed for precision calculation of the radiation safety parameters by SNF transportation use preliminary calculated Green's functions. Such approach allows quickly simulate any source distribution and optimize spent fuel assemblies placement in cask due to the transport equation property of linearity relatively the source. The short description of calculation tools are presented. Also, the paper discusses foreseen implications related to transportation of mixed-oxide SNF. (author)

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

International Nuclear Information System (INIS)

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

1985-02-01

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

Some Numbers behind Canada's Decision to Adopt an Orphan Drug Policy: US Orphan Drug Approvals in Canada, 1997-2012.

Science.gov (United States)

Herder, Matthew; Krahn, Timothy Mark

2016-05-01

We examined whether access to US-approved orphan drugs in Canada has changed between 1997 (when Canada chose not to adopt an orphan drug policy) and 2012 (when Canada reversed its policy decision). Specifically, we looked at two dimensions of access to US-approved orphan drugs in Canada: (1) regulatory access; and (2) temporal access. Whereas only 63% of US-approved orphan drugs were granted regulatory approval in 1997, we found that regulatory access to US-approved orphan drugs in Canada increased to 74% between 1997 and 2012. However, temporal access to orphan drugs is slower in Canada: in a head-on comparison of 40 matched drugs, only two were submitted and four were approved first in Canada; moreover, the mean review time in Canada (423 days) was longer than that in the US (mean = 341 days), a statistically significant difference (t[39] = 2.04, p = 0.048). These results raise questions about what motivated Canada's apparent shift in orphan drug policy. Copyright © 2016 Longwoods Publishing.

Trends in approval times for genetically engineered crops in the United States and the European Unio

NARCIS (Netherlands)

Smart, Richard D.; Blum, Matthias; Wesseler, J.H.H.

2017-01-01

Genetically engineered (GE) crops are subject to regulatory oversight to Ensure their safety for humans and the environment. Their approval in the European Union (EU) starts with an application in a given Member State followed by a scientific risk assessment, and ends with a political

The emergence of diagnostic imaging technologies in breast cancer: discovery, regulatory approval, reimbursement, and adoption in clinical guidelines.

Science.gov (United States)

Gold, Laura S; Klein, Gregory; Carr, Lauren; Kessler, Larry; Sullivan, Sean D

2012-01-25

In this article, we trace the chronology of developments in breast imaging technologies that are used for diagnosis and staging of breast cancer, including mammography, ultrasonography, magnetic resonance imaging, computed tomography, and positron emission tomography. We explore factors that affected clinical acceptance and utilization of these technologies from discovery to clinical use, including milestones in peer-reviewed publication, US Food and Drug Administration approval, reimbursement by payers, and adoption into clinical guidelines. The factors driving utilization of new imaging technologies are mainly driven by regulatory approval and reimbursement by payers rather than evidence that they provide benefits to patients. Comparative effectiveness research can serve as a useful tool to investigate whether these imaging modalities provide information that improves patient outcomes in real-world settings.

A decade of marketing approval of gene and cell-based therapies in the United States, European Union and Japan: An evaluation of regulatory decision-making.

Science.gov (United States)

Coppens, D G M; de Wilde, S; Guchelaar, H J; De Bruin, M L; Leufkens, H G M; Meij, P; Hoekman, J

2018-05-02

There is a widely held expectation of clinical advance with the development of gene and cell-based therapies (GCTs). Yet, establishing benefits and risks is highly uncertain. We examine differences in decision-making for GCT approval between jurisdictions by comparing regulatory assessment procedures in the United States (US), European Union (EU) and Japan. A cohort of 18 assessment procedures was analyzed by comparing product characteristics, evidentiary and non-evidentiary factors considered for approval and post-marketing risk management. Product characteristics are very heterogeneous and only three products are marketed in multiple jurisdictions. Almost half of all approved GCTs received an orphan designation. Overall, confirmatory evidence or indications of clinical benefit were evident in US and EU applications, whereas in Japan approval was solely granted based on non-confirmatory evidence. Due to scientific uncertainties and safety risks, substantial post-marketing risk management activities were requested in the EU and Japan. EU and Japanese authorities often took unmet medical needs into consideration in decision-making for approval. These observations underline the effects of implemented legislation in these two jurisdictions that facilitate an adaptive approach to licensing. In the US, the recent assessments of two chimeric antigen receptor-T cell (CAR-T) products are suggestive of a trend toward a more permissive approach for GCT approval under recent reforms, in contrast to a more binary decision-making approach for previous approvals. It indicates that all three regulatory agencies are currently willing to take risks by approving GCTs with scientific uncertainties and safety risks, urging them to pay accurate attention to post-marketing risk management. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Analysis of research ethics board approval times in an academic department of medicine.

Science.gov (United States)

Tsang, Teresa S M; Jones, Meaghan; Meneilly, Graydon S

2015-04-01

As part of an ongoing effort to better understand barriers to academic research, we reviewed and analyzed the process of research ethics applications, focusing on ethics approval time, within the Department of Medicine from 2006 to 2011. A total of 1,268 applications for approval to use human subjects in research were included in our analysis. Three variables, risk category (minimal vs. non-minimal risk), type of funding, and year of submission, were statistically significant for prediction of ethics approval time, with risk status being the most important of these. The covariate-adjusted mean time for approval for minimal risk studies (35.7 days) was less than half that of non-minimal risk protocols (76.5 days). Studies funded through a for-profit sponsor had significantly longer approval times than those funded through other means but were also predominantly (87%) non-minimal risk protocols. Further investigations of the reasons underlying the observed differences are needed to determine whether improved training for research ethics board (REB) members and/or greater dialogue with investigators may reduce the lengthy approval times associated with non-minimal risk protocols. © The Author(s) 2015.

13 CFR 108.380 - Final approval as a NMVC Company.

Science.gov (United States)

2010-01-01

... VENTURE CAPITAL (âNMVCâ) PROGRAM Evaluation and Selection of NMVC Companies § 108.380 Final approval as a... amount of Regulatory Capital set forth in its application, pursuant to § 108.310(a)(1); and (B) The... at least 30 percent of its Regulatory Capital if the Conditionally Approved NMVC Company— (i) Already...

Regulatory modes and time management: how locomotors and assessors plan and perceive time.

Science.gov (United States)

Amato, Clara; Pierro, Antonio; Chirumbolo, Antonio; Pica, Gennaro

2014-06-01

This research investigated the relationship between regulatory mode orientations (locomotion and assessment), time management behaviours and the perceived control of time. "Locomotion" refers to the aspect of self-regulation involving the movement from state to state, whereas "assessment" is the comparative aspect of self-regulation that refers to the critical evaluation of alternative goals and the means for achieving them. The Italian versions of the Time Management Behavior Scale and the Perceived Control of Time Scale, as well as the Locomotion and Assessment Regulatory Modes Scales were administered to 339 Italian participants (249 students and 90 employees). The results supported the notion that locomotors and assessors differ in the ways they perceive the control of time. Locomotion was found to be positively related to perceived control of time. In contrast, assessment was negatively related to perceived control of time. Furthermore, the two time management dimensions of setting goals and priorities and preference for organisation were shown to mediate the relationship between locomotion and perceived control of time, whereas assessment proved to be unrelated to all time management behaviours. These findings highlight the importance of regulatory modes for human behaviour regarding time management and perceived control of time. © 2014 International Union of Psychological Science.

Time to institutional review board approval with local versus central review in a multicenter pragmatic trial.

Science.gov (United States)

Neuman, Mark D; Gaskins, Lakisha J; Ziolek, Tracy

2018-02-01

Central institutional review board (IRB) review will be required for National Institutes of Health-funded multisite human subjects research as of January 2018, with similar requirements extending to most US multisite human research in 2020. Nonetheless, little is known regarding the relative efficiency of central versus local IRB review for multicenter studies. We compared the amount of time required for central versus local IRB review and approval for sites in one ongoing multicenter randomized trial. The REGAIN Trial (Regional versus General Anesthesia for Promoting Independence after Hip Fracture; clinicaltrials.gov number: NCT02507505) is an ongoing randomized trial comparing standard-care spinal anesthesia to standard-care general anesthesia for patients undergoing hip fracture surgery. After approval of the protocol by the sponsor IRB, each participating US site opted either to submit the protocol for local IRB review or to designate the sponsor IRB as the IRB of record (i.e. central IRB) via an authorization agreement after a limited local review. For each US REGAIN site approved through 18 April 2017, we assessed (1) the time in calendar days from protocol receipt to IRB submission, (2) the time in calendar days from IRB submission to IRB approval, and (3) the total time in calendar days from protocol receipt to IRB approval (i.e. time from protocol receipt to IRB submission plus time from IRB submission to IRB approval). The main study protocol was submitted to the sponsor IRB on 25 May 2015 and approved on 8 July 2015 (44 days). Out of 34 sites, 9 received initial approval from the central (sponsor) IRB; 25 sought initial approval via local review. The median time from protocol receipt to IRB submission was 39 days for sites approved by the central IRB (interquartile range: 35-134) versus 58 days for sites approved via local review (interquartile range: 41-105; p = 0.711). The median time from IRB submission to IRB approval for sites approved by

Accelerated approval of oncology products: the food and drug administration experience.

Science.gov (United States)

Johnson, John R; Ning, Yang-Min; Farrell, Ann; Justice, Robert; Keegan, Patricia; Pazdur, Richard

2011-04-20

We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market. From December 11, 1992, to July 1, 2010, the FDA granted accelerated approval to 35 oncology products for 47 new indications. Clinical benefit was confirmed in postapproval trials for 26 of the 47 new indications, resulting in conversion to regular approval. The median time between accelerated approval and regular approval of oncology products was 3.9 years (range = 0.8-12.6 years) and the mean time was 4.7 years, representing a substantial time savings in terms of earlier availability of drugs to cancer patients. Three new indications did not show clinical benefit when confirmatory postapproval trials were completed and were subsequently removed from the market or had restricted distribution plans implemented. Confirmatory trials were not completed for 14 new indications. The five longest intervals from receipt of accelerated approval to July 1, 2010, without completion of trials to confirm clinical benefit were 10.5, 6.4, 5.5, 5.5, and 4.7 years. The five longest intervals between accelerated approval and successful conversion to regular approval were 12.6, 9.7, 8.1, 7.5, and 7.4 years. Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time.

Global Regulatory Differences for Gene- and Cell-Based Therapies

DEFF Research Database (Denmark)

Coppens, Delphi G M; De Bruin, Marie L; Leufkens, Hubert G M

2017-01-01

Gene- and cell-based therapies (GCTs) offer potential new treatment options for unmet medical needs. However, the use of conventional regulatory requirements for medicinal products to approve GCTs may impede patient access and therapeutic innovation. Furthermore, requirements differ between...... jurisdictions, complicating the global regulatory landscape. We provide a comparative overview of regulatory requirements for GCT approval in five jurisdictions and hypothesize on the consequences of the observed global differences on patient access and therapeutic innovation....

A drug's life: the pathway to drug approval.

Science.gov (United States)

Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

2013-10-01

In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

Nuclear energy's future: lifting the regulatory cloud

International Nuclear Information System (INIS)

Walske, C.

1983-01-01

Nuclear energy provides 13% of US and 10% of world electricity, with an exemplary safety record and less insult to the environment than any other power source. Walske argues that nuclear power is 15% cheaper than coal despite the high capital and regulatory costs, but regulatory delays in the construction and licensing periods have increased 70% to 10 to 14 years, more than twice the lead time in France and Japan. The long lead time exaggerates the difficulty in forecasting demand, and allows interruptions for fundamental design changes after construction has begun. Walske outlines new legislation for site pre-approval, plant standardization, combined construction and operating licenses, and hybrid procedures for public hearings that would make regulation less uncertain

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

Science.gov (United States)

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

2016-01-01

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

7 CFR 1735.90 - Preliminary approvals.

Science.gov (United States)

2010-01-01

... AGRICULTURE GENERAL POLICIES, TYPES OF LOANS, LOAN REQUIREMENTS-TELECOMMUNICATIONS PROGRAM Requirements for... franchises, licenses, and permits; (4) All required regulatory body approvals; (5) All required corporate...

Decree 328/003. Is approve the organizational structure reformulation project of the regulatory unit of Unit 006 Energy and water services of subsection 02 Presidency of the Republic

International Nuclear Information System (INIS)

2003-01-01

This decree approve the organizational structure project of The regulatory energy and water services ( URSEA). This unit is responsible for monitoring the activities related to electricity, gas, drinking water, sanitation and oil, fuel and other hydrocarbon derivatives

The relationship between time perspective and self-regulatory processes, abilities and outcomes: a protocol for a meta-analytical review.

Science.gov (United States)

Baird, Harriet M; Webb, Thomas L; Martin, Jilly; Sirois, Fuschia M

2017-07-05

Both theoretical and empirical evidence suggests that time perspective is likely to influence self-regulatory processes and outcomes. Despite the theoretical and practical significance of such relations, the relationship between time perspective and self-regulatory processes and outcomes across different measures, samples and life domains, including health, has yet to be explored. The proposed review will develop a taxonomy for classifying measures according to the self-regulatory process, ability or outcome that they are likely to reflect. Electronic scientific databases will be searched, along with relevant conference abstract booklets and citation lists. Additionally, a call for unpublished data will be submitted to relevant bodies. To be eligible for inclusion, studies must include a measure of time perspective and a measure of at least one self-regulatory process, ability and/ or outcome. Eligibility will not be restricted by publication date, language, type of sample or setting. The bivariate correlations will be extracted (or calculated) and submitted to a random-effects meta-analysis. The sample-weighted average effect size, heterogeneity, risk of bias and publication bias will be calculated, and the effects of categorical and continuous moderator variables on the effect sizes will be determined. The proposed meta-analysis will synthesise previously conducted research; thus, ethical approval is not required. The findings will be submitted for publication in an international peer-reviewed journal and reported as part of the first author’s PhD thesis. The findings will also be disseminated to the research community and, where appropriate, to other interested parties through presentations at relevant academic and non-academic conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Time matters

NARCIS (Netherlands)

Gabbert, Silke; Hilber, Isabel

2016-01-01

A core aim of the European chemicals legislation REACH is to ensure that the risks caused by substances of very high concern (SVHC) are adequately controlled. Authorisation – i.e. the formal approval of certain uses of SVHC for a limited time - is a key regulatory instrument in order to achieve

Trends in global approvals of biotech crops (1992-2014).

Science.gov (United States)

Aldemita, Rhodora R; Reaño, Ian Mari E; Solis, Renando O; Hautea, Randy A

2015-01-01

With the increasing number of genetically modified (GM) events, traits, and crops that are developed to benefit the global population, approval of these technologies for food, feed, cultivation and import in each country may vary depending on needs, demand and trade interest. ISAAA established a GMO Approval Database to document global approvals of biotech crops. GM event name, crops, traits, developer, year of approval for cultivation, food/feed, import, and relevant dossiers were sourced from credible government regulatory websites and biosafety clearinghouses. This paper investigates the trends in GM approvals for food, feed and cultivation based on the number of approving countries, GM crops, events, and traits in the last 23 y (1992-2014), rationale for approval, factors influencing approvals, and their implications in GM crop adoption. Results show that in 2014, there was an accumulative increase in the number of countries granting approvals at 29 (79% developing countries) for commercial cultivation and 31 (70% developing countries) for food and 19 (80% developing developing) for feed; 2012 had the highest number of approving countries and cultivation approvals; 2011 had the highest number of country approvals for feed, and 2014 for food approvals. Herbicide tolerance trait had the highest events approved, followed by insect tolerance traits. Approvals for food product quality increased in the second decade. Maize had the highest number of events approved (single and stacked traits), and stacked traits product gradually increased which is already 30% of the total trait approvals. These results may indicate understanding and acceptance of countries to enhance regulatory capability to be able to benefit from GM crop commercialization. Hence, the paper provided information on the trends on the growth of the GM crop industry in the last 23 y which may be vital in predicting future GM crops and traits.

Drug lag and key regulatory barriers in the emerging markets

Directory of Open Access Journals (Sweden)

Harriet Wileman

2010-01-01

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

Trial endpoints for drug approval in oncology: Chemoprevention.

Science.gov (United States)

Beitz, J

2001-04-01

As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

The regulatory framework in the UK

International Nuclear Information System (INIS)

O'Sullivan, R.

1984-01-01

The subject is covered in sections, headed: basic regulatory requirements covering the transport of radioactive material in the UK; responsibility for safety (competent authority; provision of regulations; implementation of regulations (international and national); design of transport flask; safety case; testing; assessment; approval certificate; compliance assurance; administration); advice and information on the regulatory safety standards. (U.K.)

Trends in global approvals of biotech crops (1992–2014)

Science.gov (United States)

Aldemita, Rhodora R; Reaño, Ian Mari E; Solis, Renando O; Hautea, Randy A

2015-01-01

ABSTRACT With the increasing number of genetically modified (GM) events, traits, and crops that are developed to benefit the global population, approval of these technologies for food, feed, cultivation and import in each country may vary depending on needs, demand and trade interest. ISAAA established a GMO Approval Database to document global approvals of biotech crops. GM event name, crops, traits, developer, year of approval for cultivation, food/feed, import, and relevant dossiers were sourced from credible government regulatory websites and biosafety clearinghouses. This paper investigates the trends in GM approvals for food, feed and cultivation based on the number of approving countries, GM crops, events, and traits in the last 23 y (1992–2014), rationale for approval, factors influencing approvals, and their implications in GM crop adoption. Results show that in 2014, there was an accumulative increase in the number of countries granting approvals at 29 (79% developing countries) for commercial cultivation and 31 (70% developing countries) for food and 19 (80% developing developing) for feed; 2012 had the highest number of approving countries and cultivation approvals; 2011 had the highest number of country approvals for feed, and 2014 for food approvals. Herbicide tolerance trait had the highest events approved, followed by insect tolerance traits. Approvals for food product quality increased in the second decade. Maize had the highest number of events approved (single and stacked traits), and stacked traits product gradually increased which is already 30% of the total trait approvals. These results may indicate understanding and acceptance of countries to enhance regulatory capability to be able to benefit from GM crop commercialization. Hence, the paper provided information on the trends on the growth of the GM crop industry in the last 23 y which may be vital in predicting future GM crops and traits. PMID:26039675

30 CFR 48.3 - Training plans; time of submission; where filed; information required; time for approval; method...

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Training plans; time of submission; where filed....3 Training plans; time of submission; where filed; information required; time for approval; method... training plan shall be filed with the District Manager for the area in which the mine is located. (c) Each...

Directory of certificates of compliance for radioactive materials packages: Summary report of NRC approved packages

International Nuclear Information System (INIS)

1987-11-01

This directory contains a Summary Report of the US Nuclear Regulatory Commission's Approved Packages (Volume 1). This directory makes available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance Number is included at the back of Volume 1

The Regulatory Review Process in South Africa: Challenges and Opportunities for a New Improved System.

Science.gov (United States)

Keyter, Andrea; Gouws, Joey; Salek, Sam; Walker, Stuart

2018-01-01

The aims of this study were to assess the regulatory review process in South Africa from 2015 to 2017, identify the key milestones and timelines; evaluate the effectiveness of measures to ensure consistency, transparency, timeliness, and predictability in the review process; and to provide recommendations for enhanced regulatory practices. A questionnaire was completed by the Medicines Control Council (MCC) to describe the organization of the authority, record key milestones and timelines in the review process and to identify good review practices (GRevPs). Currently, the MCC conducts a full assessment of quality, efficacy, and safety data in the review of all applications. The overall regulatory median approval time decreased by 14% in 2017 (1411 calendar days) compared with that of 2016, despite the 27% increase in the number of applications. However, the MCC has no target for overall approval time of new active substance applications and no targets for key review milestones. Guidelines, standard operating procedures, and review templates are in place, while the formal implementation of GRevPs and the application of an electronic document management system are planned for the near future. As the MCC transitions to the newly established South Africa Health Products Regulatory Authority, it would be crucial for the authority to recognize the opportunities for an enhanced regulatory review and should consider models such as abridged assessment, which encompass elements of risk stratification and reliance. It is hoped that resource constraints may then be alleviated and capacity developed to meet target timelines.

9 CFR 317.4 - Labeling approval.

Science.gov (United States)

2010-01-01

... undue economic hardship; and (iv) An unfair competitive advantage would not result from the granting of... Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... approval to the Food Labeling Division, Regulatory Programs, Food Safety and Inspection Service, and...

76 FR 28102 - Notice of Issuance of Regulatory Guide

Science.gov (United States)

2011-05-13

... Analysis, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555... qualitative, traditional or probabilistic), data, and criteria for considering risk are appropriate for making... 10 CFR part 52, ``Licenses, Certifications, and Approvals for Nuclear Power Plants.'' Other types of...

A planning support system to optimize approval of private housing development projects

Science.gov (United States)

Hussnain, M. Q.; Wakil, K.; Waheed, A.; Tahir, A.

2016-06-01

Out of 182 million population of Pakistan, 38% reside in urban areas having an average growth rate of 1.6%, raising the urban housing demand significantly. Poor state response to fulfil the housing needs has resulted in a mushroom growth of private housing schemes (PHS) over the years. Consequently, only in five major cities of Punjab, there are 383 legal and 150 illegal private housing development projects against 120 public sector housing schemes. A major factor behind the cancerous growth of unapproved PHS is the prolonged and delayed approval process in concerned approval authorities requiring 13 months on average. Currently, manual and paper-based approaches are used for vetting and for granting the permission which is highly subjective and non-transparent. This study aims to design a flexible planning support system (PSS) to optimize the vetting process of PHS projects under any development authority in Pakistan by reducing time and cost required for site and documents investigations. Relying on the review of regulatory documents and interviews with professional planners and land developers, this study describes the structure of a PSS developed using open- source geo-spatial tools such as OpenGeo Suite, PHP, and PostgreSQL. It highlights the development of a Knowledge Module (based on regulatory documents) containing equations related to scheme type, size (area), location, access road, components of layout plan, planning standards and other related approval checks. Furthermore, it presents the architecture of the database module and system data requirements categorized as base datasets (built-in part of PSS) and input datasets (related to the housing project under approval). It is practically demonstrated that developing a customized PSS to optimize PHS approval process in Pakistan is achievable with geospatial technology. With the provision of such a system, the approval process for private housing schemes not only becomes quicker and user-friendly but also

Time perspective and social preference in older and younger adults: Effects of self-regulatory fatigue.

Science.gov (United States)

Segerstrom, Suzanne C; Geiger, Paul J; Combs, Hannah L; Boggero, Ian A

2016-09-01

Socioemotional selectivity theory predicts that when perceived time in life is limited, people will prefer emotionally close social partners over less emotionally rewarding partners. Regulating social choices with regard to time perspective can make the best use of time with regard to well-being. However, doing so may depend on the self-regulatory capacity of the individual. Two studies, 1 with younger adults (N = 101) and 1 with younger (N = 42) and older (N = 39) adults, experimentally tested the effects of time perspective and self-regulatory fatigue on preferences for emotionally close partners and knowledgeable partners. In both studies and across younger and older adults, when self-regulatory fatigue was low, the perception of limited time resulted in a greater preference for close social partners relative to knowledgeable social partners. However, this shift was eliminated by self-regulatory fatigue. In Study 2, when fatigued, younger adults preferred close social partners to knowledgeable partners across time perspectives; older adults preferred close and knowledgeable partners more equally across time perspectives. These findings have implications for social decision-making and satisfaction among people who experience chronic self-regulatory fatigue. They also contradict previous suggestions that only younger adults are susceptible to self-regulatory fatigue. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

76 FR 78706 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

Science.gov (United States)

2011-12-19

... incorporated NYSE Rule 2A (Jurisdiction) as part of the process of developing a consolidated rulebook..., among other things, rulemaking, examinations, disciplinary actions, and listing applications. NYSE Rule... executives, employees and approved persons in connection with their conduct of the business of member...

Regulatory aspects of low doses control in Albania

International Nuclear Information System (INIS)

Dollani, K.; Kushe, R.

1997-01-01

In the present paper are described the status of regulatory aspects of low doses control as well as the existing procedures for their implementation in Albania. According to new Radiological Protection Act, approved by Parliament in 1995, the establishment of the infrastructures in radiation protection area is in course, accompanied by the installation and functioning of new equipment for low dose control. Based in many years experience it is concluded that personal doses of the workers added by practices in Albania are 1/10 of dose Emits. Some particular cases of overexposured workers were investigated. Last times the elements of the optimisation procedures (QA and QC) are outlined in the frame of improving regulatory aspects of low doses control. (author)

78 FR 32077 - List of Approved Spent Fuel Storage Casks: MAGNASTOR® System

Science.gov (United States)

2013-05-29

... Fuel Storage Casks: MAGNASTOR[supreg] System AGENCY: Nuclear Regulatory Commission. ACTION: Direct... All-purpose Storage (MAGNASTOR[supreg]) System listing within the ``List of Approved Spent Fuel... CoC No. 1031, MAGNASTOR[supreg] System listing within the ``List of Approved Spent Fuel Storage Casks...

30 CFR 48.23 - Training plans; time of submission; where filed; information required; time for approval; method...

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Training plans; time of submission; where filed... Surface Mines and Surface Areas of Underground Mines § 48.23 Training plans; time of submission; where... surface mine shall have an MSHA-approved plan containing programs for training new miners, training...

National legislative and regulatory activities

International Nuclear Information System (INIS)

2015-01-01

This section treats of the following National legislative and regulatory activities: 1 - Australia: General legislation - Bill to amend the Australian Radiation Protection and Nuclear Safety Act 1998; 2 - France: General legislation - Law No. 2015-992 of 17 August 2015 on the energy transition for green growth; ASN Report on the state of nuclear safety and radiation protection in France in 2014; 3 - Germany: Radioactive waste management - First Ordinance to amend the 2005 Gorleben Development Freeze Ordinance (2015); 4 - Greece: Radioactive waste management - Joint Ministerial Decision establishing the national policy on the management of spent fuel and radioactive waste; 5 - Lithuania: Nuclear safety and radiological protection - Revised requirements for modifications, Plan for enhancement of nuclear safety, New requirements for the commissioning of nuclear power plants, Revised requirements regulating the provision of information on abnormal events; Radioactive waste management - Revised requirements for acceptance criteria for near surface repository; Nuclear security - Revised requirements for physical protection; 6 - Romania: Licensing and regulatory infrastructure - Government Decision No. 600/2014 for approval of National Nuclear Safety and Security; International co-operation - Government Decision No. 525/2014 for approval of the Co-operation Agreement on the radioactive waste management between the French National Radioactive Waste Management Agency (ANDRA) and Nuclear Agency and Radioactive Waste (ANDR) Strategy; Memorandum of Understanding for Co-operation and Exchange of Information in Nuclear Regulatory Matters between the National Commission for Nuclear Activities Control (CNCAN) of Romania and the President of National Atomic Energy Agency (PAA) of Poland; Government Decision No. 540/2015 for approval of the Agreement between the Government of Romania and the Government of the People's Republic of China regarding co-operation in the peaceful

Directory of Certificates of Compliance for Radioactive Materials Packages: Report of NRC approved packages

International Nuclear Information System (INIS)

1988-12-01

This directory contains a Report of the US Nuclear Regulatory Commission's Approved Packages (Volume 1), all Certificates of Compliance (Volume 2), and a Report of NRC Approved Quality Assurance Programs (Volume 3) for Radioactive Material Packages effective October 1, 1988. The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance Number is included at the front of Volume 2 of the directory. A listing by packaging types is included in the back of Volume 2. An alphabetical listing by Company name is included in the back of Volume 3 for approved QA programs. The Reports include a listing of all users of each package design and approved QA programs prior to the publication date of the directory

Directory of certificates of compliance for radioactive materials packages, Report of NRC approved packages

International Nuclear Information System (INIS)

1990-10-01

This directory contains a Report of the US Nuclear Regulatory Commission's Approved Packages (Volume 1), Certificates of Compliance (Volume 2), and a Report of NRC Approved Quality Assurance Programs (Volume 3) for Radioactive Materials Packages effective October 1, 1990. The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance Number is included at the front of Volume 2 of the directory. A listing by packaging types is included in the back of Volume 2. An alphabetical listing by Company name is included in the back of Volume 3 for approved QA programs. The Reports include a listing of all users of each package design and approved QA programs prior to the publication date of the directory

78 FR 16601 - List of Approved Spent Fuel Storage Casks: MAGNASTOR® System

Science.gov (United States)

2013-03-18

... Storage Casks: MAGNASTOR[supreg] System AGENCY: Nuclear Regulatory Commission. ACTION: Direct final rule... (MAGNASTOR[supreg]) System listing within the ``List of Approved Spent Fuel Storage Casks'' to include... for the MAGNASTOR[supreg] System cask design within the list of approved spent fuel storage casks that...

Regulatory issues resolved through design certification on the System 80+trademark standard plant design

International Nuclear Information System (INIS)

Ritterbusch, S.E.; Brinkman, C.B.

1996-01-01

The US Nuclear Regulatory Commission (NRC) has completed its review of the System 80+trademark Standard Plant Design, approving advanced design features and closing severe accident licensing issues. Final Design Approval was granted in July 1994. The NRC review was extensive, requiring written responses to over 4,950 questions and formal printing of over 50,000 Safety Analysis Report pages. New safety issues never before addressed in a regulatory atmosphere had to be resolved with detailed analysis and evaluation of design features. the System 80+ review demonstrated that regulatory issues can be firmly resolved only through presentation of a detailed design and completion of a comprehensive regulatory review

Patient-Centered Drug Approval: The Role of Patient Advocacy in the Drug Approval Process.

Science.gov (United States)

Mattingly, T Joseph; Simoni-Wastila, Linda

2017-10-01

Recent approval of eteplirsen for Duchenne muscular dystrophy (DMD), a rare disease with few treatment alternatives, has reignited the debate over the U.S. drug approval process. The evolution of legal and regulatory restrictions to the marketing and sale of pharmaceuticals has spanned more than a century, and throughout this history, patient advocacy has played a significant role. Scientific evidence from clinical trials serves as the foundation for drug approval, but the patient voice has become increasingly influential. Although the gold standard for establishing safety and efficacy through randomized controlled trials has been in place for more than 50 years, it poses several limitations for rare disorders where patient recruitment for traditional clinical trials is a major barrier. Organized efforts by patient advocacy groups to help patients with rare diseases access investigational therapy have had a legislative and regulatory effect. After approval by the FDA, patient access to therapy may still be limited by cost. A managed care organization (MCO) with the fiduciary responsibility of managing the health of a population must weigh coverage decisions for costly therapies with questionable effectiveness against alternatives within the constraint of a finite budget. Even when the FDA deems a drug safe and effective, an MCO may determine that the drug should only be made available at a tier level where out-of-pocket costs are still too high for many patients. This limitation of availability may be due to cost, other treatment alternatives, or outcomes from existing clinical evidence. However, if the MCO makes a costly new treatment for a rare disease readily available, it may temporarily satisfy a small contingency at the cost of all of its members. This article examines the risks and benefits of patient-centered drug approval and the potential economic effect of patient-centered drug approval on population health. There is no funding to disclose. Mattingly

Development approach on usage of radiation and inspection of QA according to the change of approval procedure of safety regulatory guides

International Nuclear Information System (INIS)

Oh, B. J.; Ahn, H. Z.; Kim, S. W.; Yoo, S. O.; Kang, S. C.; Yang, S. H.; Han, S. J.; Kim, H. S.; Kim, H. J.

2002-01-01

In accordance with 2001 amendment of the Atomic Energy Act(AEA), KINS also amended its internal 'Regulation on Implementation of Entrusted AEA-related Work'. Up to now the nuclear safety-specialized institute has used its internally developed guidelines in the safety regulation. From now on, however, the institute will enhance the objectivity and transparency by having the instruments approved by the Ministry of Science ad Technology. In this paper, we introduced the major points and directions to be considered to the development of the safety regulatory guides on Inspection for the quality assurance of the nuclear reactor facilities and the use of radioisotopes, and review and inspection for dosimeter reading

HyApproval - Handbook for the approval of hydrogen refuelling stations - First preliminary achievements

Energy Technology Data Exchange (ETDEWEB)

Wurster, R.; Vandendungen, G.; Guichard, J.; Molag, M.; Barron, J.; Reijalt, M.; Hill, H.J.; Landinger, H.

2007-05-15

The EU-funded project HyApproval [www.hyapproval.org] aims at developing a universal Handbook to facilitate the approval process of Hydrogen Refuelling Stations (HRS) in Europe. The main goal of the HyApproval partnership with 22 partners from Europe and one each from China, Japan and the USA is to provide a Handbook of technical and regulatory requirements to assist authorisation officials, companies and organisations in the safe implementation and operation of HRS. Achievements during the first 15 months: analyses of HRS technology concepts and of equipment and safety distances/ Intermediate Design Paper/ Regulations, Codes and Standards (RCS) review and comparison/ first Handbook draft and first review sessions with HySafe experts/ safety matrix/ identification of accident scenarios/ agreement on safety documentation/ critical review of reliability data from collections and risk studies/ risk assessment (RA) criteria definition and RA/ matrix of acceptability and awareness levels/ database of Fire Associations and First Responders/ calendar of hydrogen events/ general description of CGH{sub 2} interfaces. (au)

Regulatory requirements related to maintenance and compliance monitoring

International Nuclear Information System (INIS)

Ling, A.K.H.

1997-01-01

The maintenance related regulatory requirements are identified in the regulatory documents and licence conditions. Licensee complies with these requirements by operating the nuclear power plant within the safe operating envelope as given in the operating policies and principles and do maintenance according to approved procedures and/or work plans. Safety systems are regularly tested. AECB project officers review and check to ensure that the licensee operates the nuclear power plant in accordance with the regulatory requirements and licence conditions. (author). 6 tabs

2016 in review: FDA approvals of new molecular entities.

Science.gov (United States)

Griesenauer, Rebekah H; Kinch, Michael S

2017-11-01

An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long-term trends. The number of new molecular entities (NMEs) dropped, reflecting the lowest rate of small-molecule approvals observed in almost five decades. In addition, the pace of industry consolidation slowed substantially. The impact of mergers and acquisitions decreased the total number of organizations with past approval experience and continued research and development (R&D) activities to 102, divided evenly between more established pharmaceutical and newer biotechnology companies. Despite these substantial differences, the industry continued to pursue regulatory incentives, as evidenced by a continued increase in the fraction of NMEs approved using an orphan or priority designation, and almost all oncology drugs approved in 2016 utilized these mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

75 FR 51866 - Self-Regulatory Organizations; The Depository Trust Company; Order Approving Proposed Rule Change...

Science.gov (United States)

2010-08-23

... Transfer Service of National Securities Clearing Corporation August 16, 2010. I. Introduction On June 4... complements a Financial Industry Regulatory Authority (``FINRA'') rule requiring FINRA members to use... specified time frames. \\5\\ CNS is an ongoing accounting system which nets today's Settling Trades with...

Croatian energy regulatory council - independent Croatian regulatory body

International Nuclear Information System (INIS)

Klepo, M.

2002-01-01

By means of approving five energy laws, the Republic of Croatia established an appropriate legislative framework for energy sector regulation. A series of sub-law acts is presently being elaborated as well as some additional documents in order to bring about transparent and non-discriminatory provisions for the establishment of electric energy, gas, oil/oil derivatives and thermal energy markets, i.e. for the introduction and management of market activities and public services. A considerable share of these activities relates to the definition of transparent regulatory mechanisms that would guarantee the implementation of regulation rules based on the law, and be carried out by the independent regulatory body - Croatian Energy Regulatory Council. The Council's rights and obligations include firm executive functions, which present obligations to every energy entity. A dissatisfied party may set in motion a settlement of dispute, if it maintains that the decisions are not based on the law or reveal a flaw in the procedure. Therefore, it is the Council's priority to always make careful and law-abiding decisions. This paper gives insight into the regulatory framework elements based on the laws including the Council's organisational structure and non-profit entities that will prepare act proposals for the Council and perform other professional activities. (author)

75 FR 15470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Science.gov (United States)

2010-03-29

...-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule Change FINRA is proposing... (Disclosure of Price and Concessions in Selling Agreements) and the deletion of NASD Rule 2770 (Disclosure of Price in Selling Agreements). FINRA Rule 5160 was approved by the Commission on January 25, 2010 \\5\\ and...

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

Science.gov (United States)

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

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

Mining Gene Regulatory Networks by Neural Modeling of Expression Time-Series.

Science.gov (United States)

Rubiolo, Mariano; Milone, Diego H; Stegmayer, Georgina

2015-01-01

Discovering gene regulatory networks from data is one of the most studied topics in recent years. Neural networks can be successfully used to infer an underlying gene network by modeling expression profiles as times series. This work proposes a novel method based on a pool of neural networks for obtaining a gene regulatory network from a gene expression dataset. They are used for modeling each possible interaction between pairs of genes in the dataset, and a set of mining rules is applied to accurately detect the subjacent relations among genes. The results obtained on artificial and real datasets confirm the method effectiveness for discovering regulatory networks from a proper modeling of the temporal dynamics of gene expression profiles.

17 CFR 1.52 - Self-regulatory organization adoption and surveillance of minimum financial requirements.

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Self-regulatory organization... Miscellaneous § 1.52 Self-regulatory organization adoption and surveillance of minimum financial requirements. (a) Each self-regulatory organization must adopt, and submit for Commission approval, rules...

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

Science.gov (United States)

Bayarri, L

2015-08-01

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

Integration of new technology into clinical practice after FDA approval.

Science.gov (United States)

Govil, Ashul; Hao, Steven C

2016-10-01

Development of new medical technology is a crucial part of the advancement of medicine and our ability to better treat patients and their diseases. This process of development is long and arduous and requires a significant investment of human, financial and material capital. However, technology development can be rewarded richly by its impact on patient outcomes and successful sale of the product. One of the major regulatory hurdles to technology development is the Food and Drug Administration (FDA) approval process, which is necessary before a technology can be marketed and sold in the USA. Many businesses, medical providers and consumers believe that the FDA approval process is the only hurdle prior to use of the technology in day-to-day care. In order for the technology to be adopted into clinical use, reimbursement for both the device as well as the associated work performed by physicians and medical staff must be in place. Work and coverage decisions require Current Procedural Terminology (CPT) code development and Relative Value Scale Update Committee (RUC) valuation determination. Understanding these processes is crucial to the timely availability of new technology to patients and providers. Continued and better partnerships between physicians, industry, regulatory bodies and payers will facilitate bringing technology to market sooner and ensure appropriate utilization.

Directory of Certificates of Compliance for Radioactive-Materials Packages. Summary report of NRC approved packages

International Nuclear Information System (INIS)

1983-01-01

This directory contains a Summary Report of the US Nuclear Regulatory Commission's Approved Packages (Volume I), all Certificates of Compliance (Volume 2), and Summary Report of NRC Approved Quality Assurance Programs (Volume 3) for Radioactive Material Packages effective December 31, 1982. The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance Number is included at the back of Volumes 1 and 2 of the directory. A listing by packaging types is included in the back of Volume 2. An alphabetical listing by company name is included in the back of Volume 3 for approved QA programs. The Summary Reports include a listing of all users of each package design and approved QA programs prior to the publication date of the directory

Requirements, guidance and logic in planning environmental investigations: Approval versus implementation

International Nuclear Information System (INIS)

Brice, D.A.; Meredith, D.V.; Harris, M.Q.

1993-01-01

In today's litigious society, it is important for both private parties and government to plan and conduct environmental investigations in a scientifically sound manner, documenting the purpose, methods, and results in a consistent fashion throughout the exercise. Planning documents are prepared during the initial phases of environmental investigations. Project objectives, including data quality requirements, specific work to be conducted to fulfill data needs, and operating procedures are specified. Regulatory agency approval of these documents is often required prior to plan implementation. These approvals are necessary and appropriate to fulfilling the agency's mandated role. Many guidance documents prepared by regulatory agencies suggest the content and format of various scoping documents. These guidances help standardize thought processes and considerations in planning, and provide a template to ensure that both the plan and the proposed work will fulfill regulatory requirements. This work describes the preparation and use of guidance documents for planning environmental studies. The goals and some of the pitfalls of such documents are discussed. Guidance should include the following elements: the purpose of the guidance and a description of where it applies; the type of items to be addressed in planning; identification of requirements are applicable to all projects for which the guidance is intended; identification of requirements only applicable in certain situations; a description of items to facilitate planning; a suggested format for fulfilling requirements; example applications of the guidance. Disagreements arise between planners and reviewers/approvers when elements of guidance are used as leverage to require work not directly related to project objectives. Guidance may be inappropriately used as a milestone by which site-specific plans are judged. Regulatory agency review and approval may be regarded as a primary objective of the plan

77 FR 63311 - Acacia Natural Gas Corporation; Notice of Petition for Rate Approval

Science.gov (United States)

2012-10-16

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR13-1-000] Acacia Natural Gas Corporation; Notice of Petition for Rate Approval Take notice that on October 9, 2012, Acacia Natural Gas Corporation (Acacia) filed a Petition for Rate Approval pursuant to 284.123(b)(2) of the...

76 FR 41154 - Review and Approval of Projects

Science.gov (United States)

2011-07-13

..., production fluids, tophole water, and unconventional natural gas development. In order to encourage the reuse... techniques. The ``gallon one'' regulatory threshold currently applicable under the regulations to gas well... rulemaking; provide for administrative approval of interbasin transfers of flowback and production fluids...

Challenges in orphan drug development and regulatory policy in China.

Science.gov (United States)

Cheng, Alice; Xie, Zhi

2017-01-18

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

Prediction of regulatory gene pairs using dynamic time warping and gene ontology.

Science.gov (United States)

Yang, Andy C; Hsu, Hui-Huang; Lu, Ming-Da; Tseng, Vincent S; Shih, Timothy K

2014-01-01

Selecting informative genes is the most important task for data analysis on microarray gene expression data. In this work, we aim at identifying regulatory gene pairs from microarray gene expression data. However, microarray data often contain multiple missing expression values. Missing value imputation is thus needed before further processing for regulatory gene pairs becomes possible. We develop a novel approach to first impute missing values in microarray time series data by combining k-Nearest Neighbour (KNN), Dynamic Time Warping (DTW) and Gene Ontology (GO). After missing values are imputed, we then perform gene regulation prediction based on our proposed DTW-GO distance measurement of gene pairs. Experimental results show that our approach is more accurate when compared with existing missing value imputation methods on real microarray data sets. Furthermore, our approach can also discover more regulatory gene pairs that are known in the literature than other methods.

78 FR 57319 - Children's Online Privacy Protection Rule Safe Harbor Proposed Self-Regulatory Guidelines...

Science.gov (United States)

2013-09-18

...-AB20 Children's Online Privacy Protection Rule Safe Harbor Proposed Self-Regulatory Guidelines; kidSAFE... proposed self-regulatory guidelines submitted by the kidSAFE Seal Program (``kidSAFE''), owned and operated... enabling industry groups or others to submit to the Commission for approval self-regulatory guidelines that...

Novel excipients - Regulatory challenges and perspectives - The EU insight.

Science.gov (United States)

Kozarewicz, Piotr; Loftsson, Thorsteinn

2018-05-21

Novel excipients are indispensable in development of modern, advanced drug delivery systems and biotechnology-derived drugs. Although numerous novel excipients are developed for pharmaceutical use, they are not frequently seen in medicinal products due to the strict regulatory requirements and perception that their use makes new product evaluation more complex with risk of delays in the approval process. Regulators regard novel excipients as new substances and whenever new excipient is used in a formulation it must be subjected to full evaluation, similarly to the one required for new active substance. Consequently, the amount of information required in support of the regulatory approval (i.e. marketing authorization) is much more complex and comprehensive than for established excipients. This short review provides an insight into the use of novel excipients in medicinal products approved in the European Union. In addition, barriers and challenges in development of novel excipients are being discussed as well as means to overcome those barriers. Copyright © 2018 Elsevier B.V. All rights reserved.

Identifying time-delayed gene regulatory networks via an evolvable hierarchical recurrent neural network.

Science.gov (United States)

Kordmahalleh, Mina Moradi; Sefidmazgi, Mohammad Gorji; Harrison, Scott H; Homaifar, Abdollah

2017-01-01

The modeling of genetic interactions within a cell is crucial for a basic understanding of physiology and for applied areas such as drug design. Interactions in gene regulatory networks (GRNs) include effects of transcription factors, repressors, small metabolites, and microRNA species. In addition, the effects of regulatory interactions are not always simultaneous, but can occur after a finite time delay, or as a combined outcome of simultaneous and time delayed interactions. Powerful biotechnologies have been rapidly and successfully measuring levels of genetic expression to illuminate different states of biological systems. This has led to an ensuing challenge to improve the identification of specific regulatory mechanisms through regulatory network reconstructions. Solutions to this challenge will ultimately help to spur forward efforts based on the usage of regulatory network reconstructions in systems biology applications. We have developed a hierarchical recurrent neural network (HRNN) that identifies time-delayed gene interactions using time-course data. A customized genetic algorithm (GA) was used to optimize hierarchical connectivity of regulatory genes and a target gene. The proposed design provides a non-fully connected network with the flexibility of using recurrent connections inside the network. These features and the non-linearity of the HRNN facilitate the process of identifying temporal patterns of a GRN. Our HRNN method was implemented with the Python language. It was first evaluated on simulated data representing linear and nonlinear time-delayed gene-gene interaction models across a range of network sizes and variances of noise. We then further demonstrated the capability of our method in reconstructing GRNs of the Saccharomyces cerevisiae synthetic network for in vivo benchmarking of reverse-engineering and modeling approaches (IRMA). We compared the performance of our method to TD-ARACNE, HCC-CLINDE, TSNI and ebdbNet across different network

Directory of certificates of compliance for radioactive materials packages: Summary report of NRC approved quality assurance programs for radioactive material packages

International Nuclear Information System (INIS)

1987-11-01

This directory contains a Summary Report of the US Nuclear Regulatory Commission's Summary Report of NRC Approved Quality Assurance Programs (Volume 3) for Radioactive Material Packages effective October 1, 1987. This directory makes available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an alphabetical listing by Company name is included in the back of Volume 3 for approved QA programs. The Summary Reports include a listing of all users of each package design and approved QA programs prior to the publication date of the directory

Tracking of time-varying genomic regulatory networks with a LASSO-Kalman smoother

OpenAIRE

Khan, Jehandad; Bouaynaya, Nidhal; Fathallah-Shaykh, Hassan M

2014-01-01

It is widely accepted that cellular requirements and environmental conditions dictate the architecture of genetic regulatory networks. Nonetheless, the status quo in regulatory network modeling and analysis assumes an invariant network topology over time. In this paper, we refocus on a dynamic perspective of genetic networks, one that can uncover substantial topological changes in network structure during biological processes such as developmental growth. We propose a novel outlook on the inf...

Glycoconjugate Vaccines: The Regulatory Framework.

Science.gov (United States)

Jones, Christopher

2015-01-01

Most vaccines, including the currently available glycoconjugate vaccines, are administered to healthy infants, to prevent future disease. The safety of a prospective vaccine is a key prerequisite for approval. Undesired side effects would not only have the potential to damage the individual infant but also lead to a loss of confidence in the respective vaccine-or vaccines in general-on a population level. Thus, regulatory requirements, particularly with regard to safety, are extremely rigorous. This chapter highlights regulatory aspects on carbohydrate-based vaccines with an emphasis on analytical approaches to ensure the consistent quality of successive manufacturing lots.

78 FR 11639 - Houston Pipe Line Company LP; Notice of Petition for Rate Approval

Science.gov (United States)

2013-02-19

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR13-31-000] Houston Pipe Line Company LP; Notice of Petition for Rate Approval Take notice that on February 1, 2013, Houston Pipe Line Company LP (HPL) filed for approval of rates for transportation service pursuant to section...

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.

Deliberation by the French Energy Regulatory Commission of 13 July 2017 relating to the report on the implementation of GRTgaz's investment programme for 2016 and approving its amended investment programme for 2017. Deliberation by the French Energy Regulatory Commission of 13 July 2017 concerning the report on the implementation of TIGF's investment programme for 2016 and approving its amended investment programme for 2017

International Nuclear Information System (INIS)

Carenco, Jean-Francois; Chauvet, Christine; Edwige, Catherine; Gassin, Helene; Lastelle, Jean-Laurent

2017-01-01

Pursuant to the provisions of 2 of Article L.134-3 and of II of Article L.431-6 of the French Energy code, gas transmission system operators (TSOs) must transmit their annual investment programmes to the French Energy Regulatory Commission (CRE) for approval. Within this framework, CRE 'ensures that the investments required for the proper development of the networks, and for transparent and non-discriminatory access to them are made'. With regard to the investment programme for the year 2016: - in the deliberation of 17 December 2015, CRE approved GRTgaz's and TIGF's investment programmes for 2016; - in the deliberation of 15 December 2016, CRE approved the update of GRTgaz's and TIGF's 2016 investment programmes, and requested the operators to present, for mid-2017, the definitive report on the implementation of their 2016 investment programme. With regard to the investment programme for the year 2017: - in the deliberation of 15 December 2016, CRE approved GRTgaz's and TIGF's 2017 investment programmes, and requested the operators to present, for mid-2017, a report on the implementation mid-year of the investment programme for the year 2017. On 31 May 2017, GRTgaz's and TIGF's forwarded their amended investment programme for 2017 and were interviewed by CRE's Board on 6 July 2017. GRTgaz's and TIGF's presented the differences observed between the investment levels approved and the actual investments made for 2016 on the one hand, and the updated forecasts for 2017 on the other hand

Future time perspective, regulatory focus, and selection, optimization, and compensation: Testing a longitudinal model

NARCIS (Netherlands)

Baltes, B.B.; Wynne, K.; Sirabian, M.; Krenn, D.; Lange, A.H. de

2014-01-01

This study examines the behavioral processes through which future time perspective (FTP) and regulatory focus may influence coping behaviors in older workers. A three-wave longitudinal study was conducted to test a novel model, positing that FTP affects regulatory focus, which then influences the

The Ethics and Politics of Ethics Approval

Science.gov (United States)

Battin, Tim; Riley, Dan; Avery, Alan

2014-01-01

The regulatory scope of Human Research Ethics Committees can be problematic for a variety of reasons. Some scholars have argued the ethics approval process, for example, is antithetical to certain disciplines in the humanities and social sciences, while others are willing to give it qualified support. This article uses a case study to cast the…

Quality assurance within regulatory bodies

International Nuclear Information System (INIS)

1999-06-01

The IAEA directed extensive efforts during the years 1991 to 1995 to the integral revision of all NUSS quality assurance publications, which were approved and issued as Safety Series No.50-C/SG-Q, Quality Assurance for Safety in Nuclear Power Plants and other Nuclear Installations (1996). When these quality assurance publications were developed, their prime focus was on requirements against which work performed by the licensees could be measured and assessed by the regulatory bodies. In this way, they only helped to facilitate the functions of regulators. No requirements or recommendations were provided on how the regulators should ensure the effective implementation of their own activities. The present publication is a first attempt to collect, integrate and offer available experience to directly support performance of regulatory activities. It presents a comprehensive compilation on the application of quality assurance principles and methods by regulatory bodies to their activities. The aim is consistent good performance of regulatory activities through a systematic approach

18 CFR 300.10 - Application for confirmation and approval.

Science.gov (United States)

2010-04-01

... REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS FOR FEDERAL POWER MARKETING ADMINISTRATIONS CONFIRMATION AND APPROVAL OF THE RATES OF FEDERAL POWER MARKETING ADMINISTRATIONS Filing Requirements § 300.10... with applicable laws and that it is the lowest possible rate consistent with sound business principles...

The European Medicines Agency's approval of new medicines for type 2 diabetes.

Science.gov (United States)

Blind, Eberhard; Janssen, Heidi; Dunder, Kristina; de Graeff, Pieter A

2018-05-08

Since 2005, more than 40 new medicines for the treatment of type 2 diabetes have been introduced on the market. These consist of 15 new active substances establishing three new classes of non-insulin products, and several new or modified insulin products and combinations. The approval of these products in Europe is regulated via the centralized procedure at the European Medicines Agency. Demonstration of benefit with regard to improved glucose control remains the principal outcome required from confirmatory studies to demonstrate efficacy. For the majority of these new medicines approved since 2005, cardiovascular outcome trials have now been completed, and have invariably supported the cardiovascular safety of these products. In some of these trials additional important benefits have been observed, for instance, a reduction in major adverse cardiovascular events and improvement of renal outcome. The existing regulatory framework and the continuous adaption of regulatory requirements to emerging developments will continue to guide the approval of new products in the future. © 2018 John Wiley & Sons Ltd.

Benefits of standard format and content for approval of packaging for radioactive material

International Nuclear Information System (INIS)

Pstrak, D.; Osgood, N.

2004-01-01

The U.S. Nuclear Regulatory Commission (NRC) uses Regulatory Guide 7.9, ''Standard Format and Content of Part 71 Applications for Approval of Packaging for Radioactive Material'' to provide recommendations on the preparation of applications for approval of Type B and fissile material packages. The purpose of this Regulatory Guide is to assist the applicant in preparing an application that demonstrates the adequacy of a package in meeting the 10 CFR Part 71 packaging requirements. NRC recently revised Regulatory Guide 7.9 to reflect current changes to the regulations in Part 71 as a result of a recent rulemaking that included changes to the structural, containment, and criticality requirements for packages. Overall, the NRC issues Regulatory Guides to describe methods that are acceptable to the NRC staff for implementing specific parts of the NRC's regulations, to explain techniques used by the NRC staff in evaluating specific problems, and to provide guidance to applicants. It is important to note the specific purpose of this Regulatory Guide. As the name indicates, this Guide sets forth a standard format for application submission that is acceptable to the NRC staff that, when used by the applicant, will accomplish several objectives. First, use of the guide provides a consistent and repeatable approach that indicates the information to be provided by the applicant. Second, the organization of the information in the application will assist the reviewer(s) in locating information. Ultimately, accomplishing these objectives will help to ensure the completeness of the information in the application as well as decrease the review time. From an international perspective, use of a standard format approach could enhance the efficiency with which Competent Authorities certify and validate packages for use in the packaging and transportation of radioactive material worldwide. This streamlined approach of preparing package applications could ultimately lead to uniform

Competent authority approval of package designs in the United Kingdom

International Nuclear Information System (INIS)

Morgan-Warren, E.J.

1999-01-01

Type B packages and all packages containing fissile material, as well as special form radioactive materials, special arrangements and certain shipments, are required to be approved by the competent authority. In the United Kingdom competent authority approval is carried out on behalf of the Secretary of State by the Radioactive Materials Transport Division (RMTD) of the Department of the Environment, Transport and the Regions (DETR). Competent authority approval of a package design is given only after a detailed assessment of the design by the specialist staff of RMTD. There are three facets to the assessment procedure, namely engineering, criticality and radiation protection, and quality assurance. The engineering assessor ensures that the designer has demonstrated the integrity of the containment and shielding systems under the regulatory conditions. The criticality assessor examines criticality safety and radiation protection measures, and together with the engineering assessor, decides whether this is maintained under regulatory conditions. The quality assurance assessor verifies that the applicant has established the necessary controls to ensure that the design requirements are met. The applicant is responsible for making the case for approval, but the assessment is facilitated if the competent authority is involved with the designer at an early stage in development and during the construction of any test prototype. When a regulatory test programme is required, it is designed and carried out by the applicant, but agreed and witnessed by representatives of RMTD. Following the test programme, the applicant submits a formal application, supported by a design safety report (DSR). The DSR provides a full analysis of the design and the test results, including the behaviour of the package under normal and accident conditions of transport, the manufacturing and maintenance procedures, quality assurance and the emergency provisions for the operation of the package

Regulatory uncertainty and the associated business risk for emerging technologies

International Nuclear Information System (INIS)

Hoerr, Robert A.

2011-01-01

An oversight system specifically concerned with nanomaterials should be flexible enough to take into account the unique aspects of individual novel materials and the settings in which they might be used, while recognizing that heretofore unrecognized safety issues may require future modifications. This article considers a question not explicitly considered by the project team: what is the risk that uncertainty over how regulatory oversight will be applied to nanomaterials will delay or block the development of this emerging technology, thereby depriving human health of potential and substantial benefits? An ambiguous regulatory environment could delay the availability of valuable new technology and therapeutics for human health by reducing access to investment capital. Venture capitalists list regulatory uncertainty as a major reason not to invest at all in certain areas. Uncertainty is far more difficult to evaluate than risk, which lends itself to quantitative models and can be factored into projections of return on possible investments. Loss of time has a large impact on investment return. An examination of regulatory case histories suggests that an increase in regulatory resting requirement, where the path is well-defined, is far less costly than a delay of a year or more in achieving product approval and market launch.

Regulatory uncertainty and the associated business risk for emerging technologies

Science.gov (United States)

Hoerr, Robert A.

2011-04-01

An oversight system specifically concerned with nanomaterials should be flexible enough to take into account the unique aspects of individual novel materials and the settings in which they might be used, while recognizing that heretofore unrecognized safety issues may require future modifications. This article considers a question not explicitly considered by the project team: what is the risk that uncertainty over how regulatory oversight will be applied to nanomaterials will delay or block the development of this emerging technology, thereby depriving human health of potential and substantial benefits? An ambiguous regulatory environment could delay the availability of valuable new technology and therapeutics for human health by reducing access to investment capital. Venture capitalists list regulatory uncertainty as a major reason not to invest at all in certain areas. Uncertainty is far more difficult to evaluate than risk, which lends itself to quantitative models and can be factored into projections of return on possible investments. Loss of time has a large impact on investment return. An examination of regulatory case histories suggests that an increase in regulatory resting requirement, where the path is well-defined, is far less costly than a delay of a year or more in achieving product approval and market launch.

77 FR 56241 - Notice of Withdrawal of Final Design Approval; Westinghouse Electric Company; Advanced Passive 1000

Science.gov (United States)

2012-09-12

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0131] Notice of Withdrawal of Final Design Approval; Westinghouse Electric Company; Advanced Passive 1000 By letter dated December 10, 2010, Westinghouse Electric... final design approval (FDA) for the Advanced Passive 1000 (AP1000) design upon the completion of...

77 FR 12089 - Proposed Generic Communication; Regulatory Issue Summary 2012-XX: Developing Inservice Testing...

Science.gov (United States)

2012-02-28

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0048] Proposed Generic Communication; Regulatory Issue... CFR) Part 52, ``Licenses, Certifications, and Approvals for Nuclear Power Plants,'' to satisfy the... inservice testing programs during the initial 120-month program interval following nuclear power plant...

48 CFR 2052.215-77 - Travel approvals and reimbursement.

Science.gov (United States)

2010-10-01

... reimbursement. 2052.215-77 Section 2052.215-77 Federal Acquisition Regulations System NUCLEAR REGULATORY....215-77 Travel approvals and reimbursement. As prescribed at 2015.209-70(d), the contracting officer shall insert the following clause in cost reimbursement solicitations and contracts which require travel...

Avelumab: First Global Approval.

Science.gov (United States)

Kim, Esther S

2017-05-01

Avelumab (Bavencio ® ) is an intravenously administered programmed cell death ligand-1-blocking human antibody initially developed by EMD Serono Inc. (the biopharmaceutical division of Merck KGaA, Darmstadt, Germany) [now jointly developed and commercialized by EMD Serono Inc. and Pfizer] for the treatment of various tumours. It has received accelerated approval in the USA for the treatment of metastatic Merkel cell carcinoma (mMCC) in adults and paediatric patients aged ≥12 years. The marketing authorization application for avelumab in the treatment of mMCC is undergoing regulatory review in the EU, the biologics license application for avelumab in the treatment of urothelial carcinoma is undergoing priority review by the FDA, and avelumab is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of avelumab leading to this first approval for mMCC.

75 FR 51437 - Notice of Request for Extension of a Currently Approved Information Collection (Advanced Meat...

Science.gov (United States)

2010-08-20

... Request for Extension of a Currently Approved Information Collection (Advanced Meat Recovery) AGENCY: Food... information collection regarding the regulatory requirements associated with the production of meat from Advanced Meat Recovery systems because the OMB approval will expire on January 31, 2011. DATES: Comments on...

10 CFR 76.119 - Security facility approval and safeguarding of National Security Information and Restricted Data.

Science.gov (United States)

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Security facility approval and safeguarding of National Security Information and Restricted Data. 76.119 Section 76.119 Energy NUCLEAR REGULATORY COMMISSION... approval and safeguarding of National Security Information and Restricted Data. The requirements for...

Pharmacovigilance of biologicals : dynamics in post-approval safety learning

NARCIS (Netherlands)

Vermeer, N.S.

2015-01-01

Regulatory decisions to allow new drugs on the market by definition have to accept a certain level of uncertainty about the full benefit-risk balance. Pre-approval studies typically provide information on a limited number of patients over a relative short follow-up period, and handle strict

75 FR 1734 - Children’s Online Privacy Protection Rule Safe Harbor Proposed Self-Regulatory Guidelines; i-SAFE...

Science.gov (United States)

2010-01-13

... Proposed Self-Regulatory Guidelines; i-SAFE, Inc. Application for Safe Harbor AGENCY: Federal Trade... for public comment concerning proposed self-regulatory guidelines submitted by i-SAFE, Inc. under the... approval self-regulatory guidelines that would implement the Rule's protections.\\3\\ \\1\\ 64 FR 59888 (1999...

78 FR 45112 - Approval and Promulgation of Air Quality Implementation Plans; Missouri; Reasonably Available...

Science.gov (United States)

2013-07-26

... description of the VOC rule that is proposed for approval in this action is provided below. 10 CSR 10-5.455... to approve a revision to Missouri's VOC rule 10 CSR 10-5.455 into Missouri's SIP, as EPA believes... regulatory action'' subject to review by the Office of Management and Budget under Executive Order 12866 (58...

Interpretation of ALARA in the Canadian regulatory framework

Energy Technology Data Exchange (ETDEWEB)

Utting, R. [Atomic Energy Control Board, Ottawa, Ontario (Canada)

1995-03-01

The Atomic Energy Control Board (AECB) is responsible for the regulation of all aspects of atomic energy in Canada. This includes the complete nuclear fuel cycle from uranium mining to long-term disposal of nuclear fuel, as well as the medical and industrial utilization of radioisotopes. Clearly, the regulatory approach will differ from practice to practice but, as far as possible, the AECB has attempted to minimize the degree of prescription of regulatory requirements. The traditional modus operandi of the AECB has been to have broad general principles enshrined in regulations with the requirement that licensees submit specific operating policies and procedures to the AECB for approval. In the large nuclear facilities with their sophisticated technical infrastructures, this policy has been largely successful although in a changing legal and political milieu the AECB is finding that a greater degree of proactive regulation is becoming necessary. With the smaller users, the AECB has for a long time found it necessary to have a greater degree of prescription in its regulatory function. Forthcoming General Amendments to the Atomic Energy Control Regulations will, amongst other things, formally incorporate the concept of ALARA into the Canadian regulatory framework. Within the broad range of practices licensed by the AECB it is not practical to provide detailed guidance on optimization that will be relevant and appropriate to all licensees, however the following general principles are proposed.

Directory of certificates of compliance for radioactive materials packages. Volume 1. Summary report of NRC approved packages

International Nuclear Information System (INIS)

1977-12-01

Purpose of this directory is to make available a convenient source of information on packagings which have been approved by the U.S. Nuclear Regulatory Commission. This volume contains a summary report of NRC-approved packages for radioactive material packages effective Nov. 30, 1977

Global Acceptance of Biosimilars: Importance of Regulatory Consistency, Education, and Trust.

Science.gov (United States)

Cazap, Eduardo; Jacobs, Ira; McBride, Ali; Popovian, Robert; Sikora, Karol

2018-05-16

Globally, biosimilars are expected to have a key role in improving patient access to biological therapies and addressing concerns regarding the escalating cost of health care. Indeed, in Europe, increased use of biologics and reduced drug prices have been observed after the introduction of biosimilars. Recently, several monoclonal antibody biosimilars of anticancer therapies have been approved, and numerous others are in various stages of clinical development. Biosimilars are authorized via a regulatory pathway separate from that used for generic drugs; they are also regulated separately from novel biologics. Biosimilar approval pathways in many major regulatory regions worldwide are, to a broad degree, scientifically aligned. However, owing to regional differences in health care priorities, policies, and resources, some important regulatory inconsistencies are evident. Acceptance of biosimilars by health care systems, health care professionals, and patients will be a key factor in the uptake of these therapies, and such regulatory variations could contribute to confusion and diminished confidence regarding the quality, efficacy, and reliability of these agents. Furthermore, the need for manufacturers to account for regulatory inconsistencies introduces inefficiencies and delays into biosimilar development programs. These issues should be addressed if biosimilars are to attain their maximal global potential. This review summarizes the evolution of the global biosimilar landscape and provides examples of inconsistencies between regulatory requirements in different regions. In addition, we review ongoing efforts to improve regulatory alignment and highlight the importance of education as a crucial factor in generating trust in, and acceptance of, biosimilars on a worldwide scale. Biosimilars of monoclonal antibody anticancer therapies are beginning to emerge, and more are likely to become available for clinical use in the near future. The extent to which biosimilars

Biosimilars: a regulatory perspective from America.

Science.gov (United States)

Kay, Jonathan

2011-05-12

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

Directory of certificates of compliance for radioactive materials packages: Report of NRC approved quality assurance programs for radioactive material packages

International Nuclear Information System (INIS)

1988-12-01

This directory contains a Report of the US Nuclear Regulatory Commission's Approved Packages (Volume 1), all Certificates of Compliance (Volume 2), and a Report of NRC Approved Quality Assurance Programs (Volume 3) for Radioactive Material Packages effective October 1, 1988. The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance Number is included at the front of Volume 2 of the directory. A listing by packaging types is included in the back of Volume 2. An alphabetical listing by Company name is included in the back of Volume 3 for approved QA programs. The Reports include a listing of all users of each package design and approved QA programs prior to the publication date of the directory

Regulatory control of radiation sources in Slovakia

International Nuclear Information System (INIS)

Auxtova, L.

2001-01-01

In Slovakia, there are two regulatory authorities. Regulatory control of the utilization of nuclear energy, based on the Slovak National Council's law No. 130/1998 on the peaceful uses of nuclear energy, is exercised by the Nuclear Regulatory Authority of the Slovak Republic. The second regulatory authority - the Ministry of Health - is empowered by law No. 72/1994 on the protection of human health to license radiation sources and is responsible for radiation protection supervision (there are nearly 3000 establishments with sealed sources, radiation generators and unsealed sources in Slovakia). Pursuant to a new radiation protection regulation based on international standards, radiation sources are to be categorized in six classes according to the associated exposure and contamination hazards. A national strategy for improving the safety of radiation sources over their life-cycle and for the management of disused and orphan sources is being prepared for governmental approval. (author)

77 FR 26018 - Determination of Regulatory Review Period for Purposes of Patent Extension; Victoza

Science.gov (United States)

2012-05-02

... exercise to improve glycemic control in adults with type 2 diabetes mellitus. Subsequent to this approval...] Determination of Regulatory Review Period for Purposes of Patent Extension; Victoza AGENCY: Food and Drug... regulatory review period for Victoza and is publishing this notice of that determination as required by law...

Directory of certificates of compliance for radioactive materials packages. Volume 1. Summary report of NRC approved packages. Revision 6

International Nuclear Information System (INIS)

1983-09-01

This directory contains a Summary Report of the US Nuclear Regulatory Commission's Approved Packages (Volume 1), all Certificates of Compliance (Volume 2), and Summary Report of NRC Approved Quality Assurance Programs (Volume 3) for Radioactive Material Packages effective September 14, 1983

Directory of Certificates of Compliance for Radioactive Materials Packages: Report of NRC Approved Packages

International Nuclear Information System (INIS)

1993-10-01

This directory contains a Report of NRC Approved Packages (Volume 1). The purpose of this directory is to make available a convenient source of information on Quality Assurance Programs and Packagings which have been approved by the US Nuclear Regulatory Commission. Shipments of radioactive material utilizing these packagings must be in accordance with the provisions of 49 CFR section 173.471 and 10 CFR Part 71, as applicable. In satisfying the requirements of Section 71.12, it is the responsibility of the licensees to insure themselves that they have a copy of the current approval and conduct their transportation activities in accordance with an NRC approved quality assurance program

Observations on Three Endpoint Properties and Their Relationship to Regulatory Outcomes of European Oncology Marketing Applications.

Science.gov (United States)

Liberti, Lawrence; Stolk, Pieter; McAuslane, James Neil; Schellens, Jan; Breckenridge, Alasdair M; Leufkens, Hubert

2015-06-01

Guidance and exploratory evidence indicate that the type of endpoints and the magnitude of their outcome can define a therapy's clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes. We explored the relationship of 3 endpoint properties to regulatory outcomes by assessing 50 oncology marketing authorization applications (MAAs; reviewed from 2009 to 2013). Overall, 16 (32%) had a negative outcome. The most commonly used hard endpoints were overall survival (OS) and the duration of response or stable disease. OS was a component of 91% approved and 63% failed MAAs. The most commonly used surrogate endpoints were progression-free survival (PFS), response rate, and health-related quality of life assessments. There was no difference (p = .3801) between the approved and failed MAA cohorts in the proportion of hard endpoints used. A mean of slightly more than four surrogate endpoints were used per approved MAA compared with slightly more than two for failed MAAs. Longer OS and PFS duration outcomes were generally associated with approvals, often when not statistically significant. The approved cohort was associated with a preponderance of statistically significant (p < .05) improvements in primary endpoints (p < .0001 difference between the approved and failed groups). Three key endpoint properties (type of endpoint [hard/surrogate], magnitude of an endpoint outcome, and its statistical significance) are consistent with the European Medicines Agency guidance and, notwithstanding the contribution of unique disease-specific circumstances, are associated with a predictable positive outcome for oncology MAAs. Regulatory decisions made by the European Medicines Agency determine which new medicines will be available to European prescribers and for which therapeutic indications. Regulatory success or failure can be influenced by many factors. This study assessed three key properties of endpoints used in

Approving cancer treatments based on endpoints other than overall survival: an analysis of historical data using the PACE Continuous Innovation Indicators™ (CII).

Science.gov (United States)

Brooks, Neon; Campone, Mario; Paddock, Silvia; Shortenhaus, Scott; Grainger, David; Zummo, Jacqueline; Thomas, Samuel; Li, Rose

2017-01-01

There is an active debate about the role that endpoints other than overall survival (OS) should play in the drug approval process. Yet the term 'surrogate endpoint' implies that OS is the only critical metric for regulatory approval of cancer treatments. We systematically analyzed the relationship between U.S. Food and Drug Administration (FDA) approval and publication of OS evidence to understand better the risks and benefits of delaying approval until OS evidence is available. Using the PACE Continuous Innovation Indicators (CII) platform, we analyzed the effects of cancer type, treatment goal, and year of approval on the lag time between FDA approval and publication of first significant OS finding for 53 treatments approved between 1952 and 2016 for 10 cancer types (n = 71 approved indications). Greater than 59% of treatments were approved before significant OS data for the approved indication were published. Of the drugs in the sample, 31% had lags between approval and first published OS evidence of 4 years or longer. The average number of years between approval and first OS evidence varied by cancer type and did not reliably predict the eventual amount of OS evidence accumulated. Striking the right balance between early access and minimizing risk is a central challenge for regulators worldwide. We illustrate that endpoints other than OS have long helped to provide timely access to new medicines, including many current standards of care. We found that many critical drugs are approved many years before OS data are published, and that OS may not be the most appropriate endpoint in some treatment contexts. Our examination of approved treatments without significant OS data suggests contexts where OS may not be the most relevant endpoint and highlights the importance of using a wide variety of fit-for-purpose evidence types in the approval process.

An analysis of legal warnings after drug approval in Thailand.

Science.gov (United States)

Sriphiromya, Pakawadee; Theeraroungchaisri, Anuchai

2015-02-01

Drug risk management has many tools for minimizing risk and black-boxed warnings (BBWs) are one of those tools. Some serious adverse drug reactions (ADRs) emerge only after a drug is marketed and used in a larger population. In Thailand, additional legal warnings after drug approval, in the form of black-boxed warnings, may be applied. Review of their characteristics can assist in the development of effective risk mitigation. This study was a cross sectional review of all legal warnings imposed in Thailand after drug approval (2003-2012). Any boxed warnings for biological products and revised warnings which were not related to safety were excluded. Nine legal warnings were evaluated. Seven related to drugs classes and two to individual drugs. The warnings involved four main types of predictable ADRs: drug-disease interactions, side effects, overdose and drug-drug interactions. The average time from first ADRs reported to legal warnings implementation was 12 years. The triggers were from both safety signals in Thailand and regulatory measures in other countries outside Thailand. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of the new Japanese legislation for expedited approval of regenerative medicine products with the existing systems in the USA and European Union.

Science.gov (United States)

Jokura, Yoji; Yano, Kazuo; Yamato, Masayuki

2018-02-01

Legislation for expedited-approval pathways and programmes for drugs, biologics or medical devices has been enacted for rapid commercialization of innovative products in the United States of America (USA) and the European Union (EU). However, less innovative products are increasingly benefitting from these expedited-approval pathways, and obligations to collect and report post-marketing data on approved products are being bypassed frequently. The Japanese government recently enacted legislation for a new conditional and time-limited approval pathway dedicated to regenerative medicine products. The current study examines this new legislation and compares it with existing US and EU regulatory frameworks, with a particular focus on how it addresses the limitations of existing systems. Regulations, guidance documents and approval information were gathered from the websites of the respective authorities in the USA, the EU and Japan, and the systems were categorized through qualitative analysis. The pathways and programmes from each region were categorized into four groups, based on the requirement of pre- or post-marketing clinical data. Expedited-approval pathways in the USA and the EU provide similar qualification criteria, such as severity of target disease; however, such criteria are not specified for the new pathway in Japan. Only the Japanese pathway stipulates a time limitation on exceptional approval, requiring post-marketing study for conditional and time-limited products. Continuous improvement is necessary to solve previously addressed issues within the expedited-approval pathways and programmes and to ensure that innovative medical products are rigourously screened, but also readily available to patients in need. The time limitation of conditional approval could be a potential solution to some of these problems. Copyright © 2017 The Authors. Tissue Engineering Regenerative Medicine published by John Wiley & Sons, Ltd. Copyright © 2017 The Authors. Tissue

Directory of Certificates of Compliance for Radioactive-Materials Packages. Summary report of NRC approved quality assurance programs for radioactive material packages

International Nuclear Information System (INIS)

1983-01-01

This directory contains a Summary Report of the US Nuclear Regulatory Commission's Approved Packages (Volume I), all Certificates of Compliance (Volume 2), and Summary Report of NRC Approved Quality Assurance Programs (Volume 3) for Radioactive Material Packages effective December 31, 1982. The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance Number is included at the back of Volumes 1 and 2 of the directory. A listing by packaging types is included in the back of Volume 2. An alphabetical listing by Company name is included in the back of Volume 3 for approved QA programs. The Summary Reports include a listing of all users of each package design and approved QA programs prior to the publication date of the directory

Directory of Certificates of Compliance for Radioactive Materials Packages. Summary Report of NRC Approved Quality Assurance Programs for Radioactive Material Packages. Volume 3. Revision 5

International Nuclear Information System (INIS)

1985-10-01

This directory contains a Summary Report of the US Nuclear Regulatory Commission's Approved Packages (Volume I), all Certificates of Compliance (Volume 2), and Summary Report of NRC Approved Quality Assurance Programs (Volume 3) for Radioactive Material Packages effective October 1, 1985. The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance Number is included at the back of Volumes 1 and 2 of the directory. A listing by packaging types is included in the back of Volume 2. An alphabetical listing by Company name is included in the back of Volume 3 for approved QA programs. The Summary Reports include a listing of all users of each package design and approved QA programs prior to the publication date of the directory. Shipments of radioactive material utilizing these packages must be in accordance with the provisions of 49 CFR Section 173.471 and 10 CFR Part 71, as applicable. In satisfying the requirements of Section 71.12, it is the responsibility of the licensees to insure themselves that they have a copy of the current approval and conduct their transportation activities in accordance with a Nuclear Regulatory Commission approved quality assurance program. Copies of the current approval may be obtained from the US Nuclear Regulatory Commission Public Document Room files (see Docket No. listed on each certificate) at 1717 H Street, Washington, DC 20555. Note that the general license of 10 CFR Section 71.12 does not authorize the receipt, possession, use or transfer of byproduct, source or special nuclear material; such authorization must be obtained pursuant to 10 CFR Parts 30 to 36, 40, or 70

The PREEV project of the Latin American Forum.Regulatory practices on aging and life extension

International Nuclear Information System (INIS)

Figueras, J. M.

2011-01-01

The American Forum Plenary approved in 2008 the PREEV project, Regulatory Practices in Aging and Life Extension, whose main objective is to improve the regulatory action with regard to the management programs of life and long-term operation of nuclear power plants in the countries of the region Latin American.

Regulatory pathways for vaccines for developing countries.

Science.gov (United States)

Milstien, Julie; Belgharbi, Lahouari

2004-01-01

Vaccines that are designed for use only in developing countries face regulatory hurdles that may restrict their use. There are two primary reasons for this: most regulatory authorities are set up to address regulation of products for use only within their jurisdictions and regulatory authorities in developing countries traditionally have been considered weak. Some options for regulatory pathways for such products have been identified: licensing in the country of manufacture, file review by the European Medicines Evaluation Agency on behalf of WHO, export to a country with a competent national regulatory authority (NRA) that could handle all regulatory functions for the developing country market, shared manufacturing and licensing in a developing country with competent manufacturing and regulatory capacity, and use of a contracted independent entity for global regulatory approval. These options have been evaluated on the basis of five criteria: assurance of all regulatory functions for the life of the product, appropriateness of epidemiological assessment, applicability to products no longer used in the domestic market of the manufacturing country, reduction of regulatory risk for the manufacturer, and existing rules and regulations for implementation. No one option satisfies all criteria. For all options, national infrastructures (including the underlying regulatory legislative framework, particularly to formulate and implement local evidence-based vaccine policy) must be developed. WHO has led work to develop this capacity with some success. The paper outlines additional areas of action required by the international community to assure development and use of vaccines needed for the developing world. PMID:15042235

Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling

Directory of Open Access Journals (Sweden)

Guo Zheng

2006-01-01

Full Text Available Abstract Background It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. Results In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network to address the underlying regulations of genes that can span any unit(s of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. Conclusion We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex

Regulatory compliance guide for DOT-7A type A packaging design

International Nuclear Information System (INIS)

Kelly, D.L.

1996-01-01

The purpose of this guide is to provide instruction for assuring that the regulatory design requirements for a DOT-7A Type A packaging are met. This guide also supports the testing and evaluation activities that are performed on new packaging designs by a DOE-approved test facility through the DOE's DOT-7A Test Program. This Guide was updated to incorporate regulatory changes implemented by HM-169A (49 CFR, 'Transportation')

Factors related to drug approvals: predictors of outcome?

Science.gov (United States)

Liberti, Lawrence; Breckenridge, Alasdair; Hoekman, Jarno; McAuslane, Neil; Stolk, Pieter; Leufkens, Hubert

2017-06-01

There is growing interest in characterising factors associated with positive regulatory outcomes for drug marketing authorisations. We assessed empirical studies published over the past 15 years seeking to identify predictive factors. Factors were classified to one of four 'factor clusters': evidentiary support; product or indication characteristics; company experience or strategy; social and regulatory factors. We observed a heterogeneous mix of technical factors (e.g., study designs, clinical evidence of efficacy) and less studied social factors (e.g., company-regulator interactions). We confirmed factors known to be of relevance to drug approval decisions (imperative) and a cohort of less understood (compensatory) social factors. Having robust supportive clinical evidence, addressing rare or serious illness, following scientific advice and prior company experience were associated with positive outcomes, which illustrated the multifactorial nature of regulatory decision making and factors need to be considered holistically while having varying, context-dependent importance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Approval of raxibacumab for the treatment of inhalation anthrax under the US Food and Drug Administration Animal rule

Directory of Open Access Journals (Sweden)

Chia-Wei eTsai

2015-12-01

Full Text Available On December 14, 2012, the FDA approved raxibacumab, the first product developed under Project BioShield to achieve this milestone, and the first biologic product to be approved through the FDA animal efficacy rule (or Animal Rule. Raxibacumab is approved for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibiotic drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate. The approval of Raxibacumab illustrates many of the challenges that product developers may encounter when pursuing approval under the Animal Rule and highlights a number of important regulatory and policy issues.

The reform of the Moldovan nuclear and radiological regulatory infrastructure

International Nuclear Information System (INIS)

Buzdugan, Artur

2008-01-01

Establishment of an independent and efficient regulatory body was recognized as a high level state priority in the last years. On May 11, 2006, the Parliament approved the new Law 111-XVI 'On safe deployment of nuclear and radiological activities'. According to the Law, there is being established a single regulatory body - National Agency for Regulation of Nuclear and Radiological Activities (further 'Regulator') and replaced those four domestic domestic regulatory bodies, being earlier in force. On february 28, 2007, the government has approved its Regulation and structure. The Regulator is established under the Ministry of Ecology and Natural Resources, but having the necessary financial and decision independence, The Director General of the Regulator is appointed by the Prime-Minister upon the recommendation of the respective Minister. The Regulator is responsible for the authorization, review and assessment on regulation, norms, inspection and enforcement. The mains kinds of activities with ionizing radiation sources are subjects of authorization by licensing of registration. The authorizations are issued if the user respects fully the conditions of legal norms forwarded by the Regulator. Authorizations are delivered under the form of license or certificates of registration, respective for I-III or IV-V categories of used ionizing radiation sources. For the first time, it is introduced in practice the categorization of radioactive sources, based on IAEA recommendations. Certificates of registration are issued by the Regulator, contrary to the licenses, which are issued or revoked by the Chamber of Licensing, on the base of the Regulator written notification. All services of the Regulator are free of charge. The Inspectorate is established as the subdivision of the Regulator. It is subordinated directly to the Director General of the Regulator, who is the Main State Inspector from the office. The inspectors have the right to perform inspections independent or

Regulatory Aspects of Sabin Type 2 Withdrawal From Trivalent Oral Poliovirus Vaccine: Process and Lessons Learned.

Science.gov (United States)

Decina, Daniela; Fournier-Caruana, Jacqueline; Takane, Marina; Ostad Ali Dehaghi, Razieh; Sutter, Roland

2017-07-01

Withdrawal of type 2 oral poliovirus vaccine (OPV) in OPV-using countries required regulatory approval for use of inactivated poliovirus vaccine and bivalent OPV in routine immunization. Worldwide, a variety of mechanisms were used by member states, with some differences in approach observed between inactivated poliovirus vaccine and bivalent OPV. These included acceptance for use of World Health Organization (WHO) prequalified vaccines, registration and licensure pathways, participation in WHO-convened joint reviews of licensing dossiers, as well as pragmatic application of alternatively available mechanisms, when appropriate. Simple but effective tools were used to monitor progress and to record, authenticate, and share information. Essential to achievement of regulatory targets was ongoing communication with key stakeholders, including switch-country national regulatory authorities, vaccine manufacturers, partner organizations, and relevant units within WHO. Understanding of the regulatory environment gained through the OPV switch can be helpful in supporting further stages of the polio end game and other time-sensitive vaccine introduction programs. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Radiological Medical Device Innovation: Approvals via the Premarket Approval Pathway From 2000 to 2015.

Science.gov (United States)

Ghobadi, Comeron W; Hayman, Emily L; Finkle, Joshua H; Walter, Jessica R; Xu, Shuai

2017-01-01

The aim of this study was to critically assess the clinical evidence leading to radiologic medical device approvals via the premarket approval pathway from 2000 to 2015. This study used the publically available FDA premarket database for radiologic device approvals over the past 15 years (September 1, 2000, to August 31, 2015). Approval characteristics were collected for each device, and statistical analysis was performed on the data for each pivotal trial. Additionally, methodological quality of the pivotal trial was determined using the Quality Assessment of Diagnostic Accuracy Studies tool. Twenty-three class III radiologic device approvals were identified, with breast imaging accounting for 16 (70%) and computer-aided detection software accounting for 9 (39%) approvals. The median premarket approval time was 475 days (range, 180-1,116). Twenty-one devices were approved on the basis of multireader, multicenter studies, one on the basis of a randomized controlled trial, and one on the basis of a preclinical technical equivalence trial. The median number of patients per pivotal trial was 201 (range, 25-3,946). Twenty-six of the 34 pivotal trials (76%) had at least one methodologic bias. Breast imaging devices had a greater number of patients per pivotal trial (P = .009) and more prospective studies. With regard to all modalities, increased time to device approval correlated with weaker trial quality (r = 0.600, P assessing diagnostic technologies. Given that radiologic devices play a key role in modern medicine, further efforts should be made to increase transparency of clinical data leading to approval. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

30 CFR 948.15 - Approval of West Virginia regulatory program amendments.

Science.gov (United States)

2010-07-01

..., 2008 CSR 38-2-2.39 (deletion of cumulative impact definition).CSR 38-2-3.22.e (approval of material... Legislative Rules at title 38, Series 2. June 29, 1990 October 4, 1991 CSR 38-2 §§ 2, 3, 5, 6, 9, 11 through 14, 17, 20, 22. July 12, 1991 November 19, 1991 CSR 38-2-20.5, .6, .7. July 30, 1993 August 16, 1995...

Digital mammography. Why hasn't it been approved for U.S. hospitals?

Science.gov (United States)

2000-01-01

Mammography is the only major imaging technique still unavailable in the United States in digital form. This is because the Food and Drug Administration (FDA) has been unable to devise an effective method for manufacturers to demonstrate the safety and efficacy of digital mammography systems. As a result, the agency has been unable to approve any of those systems for marketing in the United States. In this Regulatory Update, we describe FDA's recent efforts to help manufacturers obtain approval and the reasons those efforts have so far proved ineffective.

REVIEW OF NRC APPROVED DIGITAL CONTROL SYSTEMS ANALYSIS

International Nuclear Information System (INIS)

Markman, D.W.

1999-01-01

Preliminary design concepts for the proposed Subsurface Repository at Yucca Mountain indicate extensive reliance on modern, computer-based, digital control technologies. The purpose of this analysis is to investigate the degree to which the U. S. Nuclear Regulatory Commission (NRC) has accepted and approved the use of digital control technology for safety-related applications within the nuclear power industry. This analysis reviews cases of existing digitally-based control systems that have been approved by the NRC. These cases can serve as precedence for using similar types of digitally-based control technologies within the Subsurface Repository. While it is anticipated that the Yucca Mountain Project (YMP) will not contain control systems as complex as those required for a nuclear power plant, the review of these existing NRC approved applications will provide the YMP with valuable insight into the NRCs review process and design expectations for safety-related digital control systems. According to the YMP Compliance Program Guidance, portions of various NUREGS, Regulatory Guidelines, and nuclear IEEE standards the nuclear power plant safety related concept would be applied to some of the designs on a case-by-case basis. This analysis will consider key design methods, capabilities, successes, and important limitations or problems of selected control systems that have been approved for use in the Nuclear Power industry. An additional purpose of this analysis is to provide background information in support of further development of design criteria for the YMP. The scope and primary objectives of this analysis are to: (1) Identify and research the extent and precedence of digital control and remotely operated systems approved by the NRC for the nuclear power industry. Help provide a basis for using and relying on digital technologies for nuclear related safety critical applications. (2) Identify the basic control architecture and methods of key digital control

Overcoming regulatory challenges in the development of companion diagnostics for monitoring and safety.

Science.gov (United States)

Shimazawa, Rumiko; Ikeda, Masayuki

2016-03-01

Concurrent development and co-approval of a companion diagnostic (CDx) with a corresponding drug is ideal, but often unfeasible. Because of limited exposure to a drug in clinical trials, crucial information on safety is sometimes revealed only after approval. Therefore, a CDx for monitoring/safety is often developed after approval of a corresponding drug. However, regulatory guidance is insufficient if contemporaneous development is not possible, thereby leaving plenty of opportunities for improvement with respect to pharmacovigilance and retrospective validation of the CDx. Furthermore, global harmonization of guidance on how to incorporate new scientific information from retrospective analyses of biomarkers should lead to the establishment of more evidence for the development of CDx for approved drugs.

Electronic Approval of Invoices (AEF)

CERN Document Server

2004-01-01

With a view to the simplification of administrative procedures, AS and FI Departments have completed the second phase of the new procedure for the electronic approval of invoices via the EDH application. The aim of this new procedure is to rationalise the invoice approval process, notably by eliminating paper copies from the approval circuit. This will simplify the processing of invoices and facilitate their timely settlement, while at the same time maintaining a high level of security. Phase II includes handling the electronic approval process of invoices whose amounts do not correspond exactly to those of the associated orders. In such cases, budgetary approval is required for the entire invoiced amount. Further information can be obtained at : http://ais.cern.ch/projs/AEF/help/F_help.htm Phase II of the procedure will be introduced gradually with effect from April 2004. Finance Department, Accounts Payable Section Tel: 72295 Organisation and Procedures Tel: 75885 Information Technologies Department,...

Methodological challenges for the evaluation of clinical effectiveness in the context of accelerated regulatory approval: an overview.

Science.gov (United States)

Woolacott, Nerys; Corbett, Mark; Jones-Diette, Julie; Hodgson, Robert

2017-10-01

Regulatory authorities are approving innovative therapies with limited evidence. Although this level of data is sufficient for the regulator to establish an acceptable risk-benefit balance, it is problematic for downstream health technology assessment, where assessment of cost-effectiveness requires reliable estimates of effectiveness relative to existing clinical practice. Some key issues associated with a limited evidence base include using data, from nonrandomized studies, from small single-arm trials, or from single-center trials; and using surrogate end points. We examined these methodological challenges through a pragmatic review of the available literature. Methods to adjust nonrandomized studies for confounding are imperfect. The relative treatment effect generated from single-arm trials is uncertain and may be optimistic. Single-center trial results may not be generalizable. Surrogate end points, on average, overestimate treatment effects. Current methods for analyzing such data are limited, and effectiveness claims based on these suboptimal forms of evidence are likely to be subject to significant uncertainty. Assessments of cost-effectiveness, based on the modeling of such data, are likely to be subject to considerable uncertainty. This uncertainty must not be underestimated by decision makers: methods for its quantification are required and schemes to protect payers from the cost of uncertainty should be implemented. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

75 FR 75678 - Determination of Regulatory Review Period for Purposes of Patent Extension; STELARA

Science.gov (United States)

2010-12-06

..., animal drug product, medical device, food additive, or color additive) was subject to regulatory review... or systemic therapy. Subsequent to this approval, the Patent and Trademark Office received a patent...

Technology Overview Using Case Studies of Alternative Landfill Technologies and Associated Regulatory Topics

National Research Council Canada - National Science Library

2003-01-01

... alternative landfill cover projects. The purpose of the case studies is to present examples of the flexibility used in the regulatory framework for approving alternative landfill cover designs, current research information about the use...

Biosimilars in psoriasis: Clinical practice and regulatory perspectives in Latin America.

Science.gov (United States)

de la Cruz, Claudia; de Carvalho, André V E; Dorantes, Gladys L; Londoño Garcia, Angela M; Gonzalez, Cesar; Maskin, Matías; Podoswa, Nancy; Redfern, Jan S; Valenzuela, Fernando; van der Walt, Joelle; Romiti, Ricardo

2017-01-01

Latin American countries view biosimilar agents as an effective approach to curtail health-care expenditures while maintaining the safety and efficacy profile of their branded innovator comparators. To understand the complexities of the regulatory landscape and key therapeutic issues for use of biosimilars to treat moderate to severe psoriasis in Latin America, the International Psoriasis Council convened dermatology experts from Argentina, Brazil, Chile, Colombia and Mexico in October 2015 to review the definition, approval, marketing and future of biosimilars in each country and develop a consensus statement. The regulatory framework for marketing approval of biosimilars in Latin America is currently a mosaic of disparate, country-specific, regulatory review processes, rules and standards, with considerable heterogeneity in clarity and specificity. Regulations in Argentina, Brazil, Chile and Mexico have undergone multiple refinements whereas Colombia is finalizing draft guidelines. Verification of the similarity in quality, safety and efficacy of biosimilars to the innovator biologic remains a key challenge for policy makers and regulatory authorities. Other key regulatory challenges include: naming of agents and traceability, pharmacovigilance, extrapolation of indications, and interchangeability and substitution. An urgent need exists for more Latin American countries to establish national psoriasis registries and to integrate their common components into a multinational psoriasis network, thereby enhancing their interpretative power and impact. A Latin American psoriasis network similar to PSONET in Europe would assist health-care providers, pharmaceutical companies, regulators and patients to fully comprehend specific products being prescribed and dispensed and to identify potential regional trends or differences in safety or outcomes. © 2016 Japanese Dermatological Association.

Global Stability of Complex-Valued Genetic Regulatory Networks with Delays on Time Scales

Directory of Open Access Journals (Sweden)

Wang Yajing

2016-01-01

Full Text Available In this paper, the global exponential stability of complex-valued genetic regulatory networks with delays is investigated. Besides presenting conditions guaranteeing the existence of a unique equilibrium pattern, its global exponential stability is discussed. Some numerical examples for different time scales.

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

Science.gov (United States)

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

2018-05-25

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

Regulatory Approval Decisions in the Presence of Market Externalities: The Case of Genetically Modified Wheat

OpenAIRE

Furtan, William Hartley; Gray, Richard S.; Holzman, J.J.

2005-01-01

This study examines the optimal approval strategy for genetically modified (GM) wheat varieties in Canada and the United States. Without an affordable segregation system, the introduction of GM wheat will create a market for "lemons" that will result in the loss of important export markets. Using a differentiated product trade model for spring wheat, with endogenous technology pricing, a payoff matrix is generated for the possible approval outcomes. Results show that the existence of the mark...

75 FR 27340 - Enterprise Alabama Intrastate, LLC; Notice of Petition for Rate Approval

Science.gov (United States)

2010-05-14

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-21-000] Enterprise..., Enterprise Alabama Intrastate, LLC (Enterprise Alabama) filed a petition for rate approval pursuant to section 284.123(b)(2) of the Commission's regulations. Enterprise Alabama states it is filing to justify...

A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Multiple Myeloma.

Science.gov (United States)

Raju, G K; Gurumurthi, Karthik; Domike, Reuben; Kazandjian, Dickran; Landgren, Ola; Blumenthal, Gideon M; Farrell, Ann; Pazdur, Richard; Woodcock, Janet

2018-01-01

Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analysis. In this work, a quantitative benefit-risk analysis approach captures regulatory decision-making about new drugs to treat multiple myeloma (MM). MM assessments have been based on endpoints such as time to progression (TTP), progression-free survival (PFS), and objective response rate (ORR) which are different than benefit-risk analysis based on overall survival (OS). Twenty-three FDA decisions on MM drugs submitted to FDA between 2003 and 2016 were identified and analyzed. The benefits and risks were quantified relative to comparators (typically the control arm of the clinical trial) to estimate whether the median benefit-risk was positive or negative. A sensitivity analysis was demonstrated using ixazomib to explore the magnitude of uncertainty. FDA approval decision outcomes were consistent and logical using this benefit-risk framework. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Safety regulation for the design approval of special form radioactive sources

International Nuclear Information System (INIS)

Cho, Woon-Kap

2009-01-01

Several kinds of special form radioactive sources for industrial, medical applications are being produced in Korea. Special form radioactive sources should meet strict safety requirements specified in the domestic safety regulations and the design of the sources should be certified by the regulatory authority, the Ministry of Education, Science and Technology (MEST). Several safety tests such as impact, percussion, heating, and leak tests are performed on the sources according to the domestic regulations and the international safety standards such as ANSI N542-1977 and ISO 2919-1999(E). As a regulatory expert body, Korea Institute of Nuclear Safety (KINS) assesses various types of application documents, such as safety analysis report, quality assurance program, and other documents evidencing fulfillment of requirements for design approval of the special form radioactive sources, submitted by a legal person who intends to produce special form radioactive sources and then reports the assessment result to MEST. A design approval certificate is issued to the applicant by MEST on the basis of a technical evaluation report presented by KINS.

Longitudinal evaluation of a World Wide Web-based antimicrobial stewardship program: assessing factors associated with approval patterns and trends over time.

Science.gov (United States)

Venugopal, Vidya; Lehmann, Christoph U; Diener-West, Marie; Agwu, Allison L

2014-02-01

The Johns Hopkins Children's Medical and Surgery Center developed a Web-based Antimicrobial Stewardship Program (ASP) in 2005. The present study aimed to assess longitudinal antimicrobial request and approval patterns for this ASP. We analyzed a total of 16,229 antimicrobial requests for 3,542 patients between June 1, 2005, and June 30, 2009. Antimicrobial approval was the outcome of interest. We assessed gaming by studying trends in automatically approved requests. Nonparametric tests for trend were performed to detect changes in approval patterns. Multiple logistic regression was used to identify factors associated with approval. The vast majority (91.3%) of antimicrobial requests were approved, with an increase of 6.1% over time (P Web-based ASP allows management of a large number of antimicrobial requests, without apparent gaming. Observed differences in approval patterns based on patient, requestor, and antimicrobial factors may inform the development of ASPs and evaluation of provider education and training. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Interactive visualization of gene regulatory networks with associated gene expression time series data

NARCIS (Netherlands)

Westenberg, M.A.; Hijum, van S.A.F.T.; Lulko, A.T.; Kuipers, O.P.; Roerdink, J.B.T.M.; Linsen, L.; Hagen, H.; Hamann, B.

2008-01-01

We present GENeVis, an application to visualize gene expression time series data in a gene regulatory network context. This is a network of regulator proteins that regulate the expression of their respective target genes. The networks are represented as graphs, in which the nodes represent genes,

Ethical and regulatory problems of molecular imaging

International Nuclear Information System (INIS)

Jeong, Jae Min

2004-01-01

As a molecular imaging is the most up-to-date technology in nuclear medicine, it has complicate ethical and regulatory problems. For animal experiment, we have to follow institutional animal care committee. For clinical experiment, we have to get approval of Institutional Review Board according to Helsinki declaration. In addition, approval from Korea Food and Drug Administration (KFDA) is essential for manufacturing and commercialization. However, too much regulation would suppress development of new technology, which would result in the loss of national competitive power. In addition, most new radioactive ligands for molecular imaging are administered to human at sub-pharmacological and sub-toxicological level. In conclusion, a balanced regulation is essential for the safety of clinical application and development of new technology

Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants.

Science.gov (United States)

Ma, Julian K-C; Drossard, Jürgen; Lewis, David; Altmann, Friedrich; Boyle, Julia; Christou, Paul; Cole, Tom; Dale, Philip; van Dolleweerd, Craig J; Isitt, Valerie; Katinger, Dietmar; Lobedan, Martin; Mertens, Hubert; Paul, Mathew J; Rademacher, Thomas; Sack, Markus; Hundleby, Penelope A C; Stiegler, Gabriela; Stoger, Eva; Twyman, Richard M; Vcelar, Brigitta; Fischer, Rainer

2015-10-01

Although plant biotechnology has been widely investigated for the production of clinical-grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma-Planta project, the HIV-neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant-derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant-derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first-in-human, double-blind, placebo-controlled, randomized, dose-escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant-derived pharmaceutical proteins. © 2015 Society for Experimental Biology, Association of

Regulatory acceptance of the proposed well abandonment program for the present landfill, Operable Unit 7, Rocky Flats Environmental Technology Site, Golden, Colorado

International Nuclear Information System (INIS)

Wood, M.R.

1995-01-01

The regulatory agencies approved a well abandonment program for the Present Landfill, Operable Unit (OU) 7 at the Rocky Flats Environmental Technology Site, only three months after preparation. The proposed well abandonment program consists of abandoning 26 of the 54 existing monitoring wells in OU 7 that are currently sampled quarterly as Resource Conservation and Recovery Act (RCRA) compliance wells or sitewide groundwater protection wells. Well abandonment was proposed on the basis that the purpose of each well has been fulfilled, the wells fall under the footprint of the landfill cap, the presence of the wells would compromise the integrity of the cap because holes would have to be cut in the synthetic liner, and unequal compaction of the fill material around the wells would potentially cause differential settlement of the cap. The proposal provided the technical justification to abandon the wells in place. The timely approval of the proposal by the regulatory agencies will allow the abandonment of the wells during fiscal year 1995 under the sitewide Well Abandonment and Replacement Program (WARP). Cost savings resulting from a decrease in the number of wells to be sampled under the groundwater monitoring program are estimated at $416,000 per year. This paper presents a summary of the well abandonment program, discusses the timely approvals required for implementation, and present the potential cost savings that can be achieved through implementation of the program

Innovative farmers and regulatory gatekeepers: Genetically modified crops regulation and adoption in developing countries.

Science.gov (United States)

Sinebo, Woldeyesus; Maredia, Karim

2016-01-02

The regulation of genetically modified (GM) crops is a topical issue in agriculture and environment over the past 2 decades. The objective of this paper is to recount regulatory and adoption practices in some developing countries that have successfully adopted GM crops so that aspiring countries may draw useful lessons and best practices for their biosafatey regulatory regimes. The first 11 mega-GM crops growing countries each with an area of more than one million hectares in 2014 were examined. Only five out of the 11 countries had smooth and orderly adoption of these crops as per the regulatory requirement of each country. In the remaining 6 countries (all developing countries), GM crops were either introduced across borders without official authorization, released prior to regulatory approval or unapproved seeds were sold along with the approved ones in violation to the existing regulations. Rapid expansion of transgenic crops over the past 2 decades in the developing world was a result of an intense desire by farmers to adopt these crops irrespective of regulatory roadblocks. Lack of workable biosafety regulatory system and political will to support GM crops encouraged unauthorized access to GM crop varieties. In certain cases, unregulated access in turn appeared to result in the adoption of substandard or spurious technology which undermined performance and productivity. An optimal interaction among the national agricultural innovation systems, biosafety regulatory bodies, biotech companies and high level policy makers is vital in making a workable regulated progress in the adoption of GM crops. Factoring forgone opportunities to farmers to benefit from GM crops arising from overregulation into biosafety risk analysis and decision making is suggested. Building functional biosafety regulatory systems that balances the needs of farmers to access and utilize the GM technology with the regulatory imperatives to ensure adequate safety to the environment and human

77 FR 26290 - Determination of Regulatory Review Period for Purposes of Patent Extension; KRYSTEXXA

Science.gov (United States)

2012-05-03

..., medical device, food additive, or color additive) was subject to regulatory review by FDA before the item... chronic gout in adult patients refractory to conventional therapy. Subsequent to this approval, the Patent...

HIV testing updates and challenges: when regulatory caution and public health imperatives collide.

Science.gov (United States)

Branson, Bernard M

2015-03-01

Numerous improvements in HIV testing technology led recently to the first revision of recommendations for diagnostic laboratory testing in the USA in 25 years. Developments in HIV testing continue to produce tests that identify HIV infection earlier with faster turnaround times for test results. These play an important role in identifying HIV infection during the highly infectious acute phase, which has implication for both patient management and public health interventions to control the spread of HIV. Access to these developments, however, is often delayed by the regulatory apparatus for approval and oversight of HIV testing in the USA. This article summarizes recent developments in HIV diagnostic testing technology, outlines their implications for clinical management and public health, describes current systems of regulatory oversight for HIV testing in the USA, and proposes alternatives that could expedite access to improved tests as they become available.

Quality assurance test of a real time radiography system

International Nuclear Information System (INIS)

Yadav, R.K.; Rama, R.; Sharma, A.; Kannan, R.

2005-01-01

Any radiation generating equipment can be used and marketed in India only after obtaining specific type approval certificate from the Competent Authority i.e. Chairman, Atomic Energy Regulatory Board (AERB), Mumbai. Recently AERB has enforced a directive that the Industrial X-ray machines should also be permitted to use only after getting NOC or type approval. Type approval is granted based upon the satisfactory QA test report of the radiation generating equipment. X-ray machines with Real Time Radiography (RTR) facility are used in industrial radiography for faster inspection of equipment's and products online. A standard test protocol was developed for QA tests of a real time radiography system. This will be helpful for evaluation of an industrial X-ray machine. Also above procedure can be used to check a RTR system each day or a system-qualification can be done when the image quality diminishes as recommended by American Society of Testing Material (ASTM). Various tests carried out on a constant potential 450 kV, 10 mA industrial X-ray machine having real time radiography facility to monitor the products online, is described in this paper. (author)

75 FR 19645 - Enterprise Texas Pipeline LLC; Notice of Petition for Rate Approval

Science.gov (United States)

2010-04-15

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-14-000] Enterprise..., 2010, Enterprise Texas Pipeline LLC (Enterprise Texas) filed a petition for rate approval pursuant to section 284.123(b)(2) of the Commission's regulations. Enterprise Texas proposes rates of $0.6090 per...

Status report on NRC's current below regulatory concern activities

International Nuclear Information System (INIS)

Dragonette, K.S.

1988-01-01

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

75 FR 64771 - Self-Regulatory Organizations; Order Approving Minor Rule Violation Plan for BATS Y-Exchange, Inc.

Science.gov (United States)

2010-10-20

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63113; File No. 4-616] Self-Regulatory... provisions of Rule 19d-1(c)(1) of the Act \\4\\ requiring that a self-regulatory organization promptly file... Commission adopted amendments to paragraph (c) of Rule 19d-1 to allow self-regulatory organizations (``SROs...

77 FR 4203 - List of Approved Spent Fuel Storage Casks: MAGNASTOR® System, Revision 2

Science.gov (United States)

2012-01-27

... Storage Casks: MAGNASTOR[supreg] System, Revision 2 AGENCY: Nuclear Regulatory Commission. ACTION: Direct... storage regulations by revising the NAC International, Inc. (NAC) MAGNASTOR[supreg] System listing within the ``List of Approved Spent Fuel Storage Casks'' to include Amendment No. 2 to Certificate of...

75 FR 33736 - List of Approved Spent Fuel Storage Casks: MAGNASTOR System, Revision 1

Science.gov (United States)

2010-06-15

... Fuel Storage Casks: MAGNASTOR System, Revision 1 AGENCY: Nuclear Regulatory Commission. ACTION... storage cask regulations by revising the NAC International, Inc. (NAC), MAGNASTOR System listing within the ``List of Approved Spent Fuel Storage Casks'' to include Amendment No. 1 to Certificate of...

Miracle drug: Brazil approves never-tested cancer medicine.

Science.gov (United States)

Kuchenbecker, Ricardo S; Mota, Daniel M

2017-07-01

Background Brazil recently approved synthetic phosphoetanolamine, a popularly dubbed 'cancer pill', a substance that has been shown to kill cancer cells in lab animal models but was not yet formally accessed in humans, and thus despite the existence of any evidence of its efficacy and safety. Methods The authors describe the recent decision of Brazil to aprove phosphoetanolamine in the context of growing 'judicialization' to promote access to medicines and thus reinforcing a growing sense of legal uncertainty. Results The approval of phosphoetanolamine despite the existence of any evidence of its efficacy and safety represents to the authors one of the saddest and surrealistic episodes in Brazil's recent public health history. Brazil's current economic crisis is fueling the 'judicialization' to promote access to medicines and thus reinforcing a growing sense of legal uncertainty in the context of rising economic constrains and a progressive failing state. The authors state that the Phosphoetanolamine's approval bill violates current legal prohibition of commercialisation of drugs without the Brazilian national drug regulatory agency's approval and thus may represent a potential menace to Brazil's pharmacogovernance and the country's governance to health technology assessment at the Brazilian national health systems. Conclusion Phosphoetanolamine's approval illustrates that the combination of flawed decision making, economic crisis and political interference may threaten weak governance mechanisms for drug regulation and health technology assessment and thus representing an extra burden in the sustainability of universal access-based national health systems.

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

Science.gov (United States)

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

2017-12-01

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

1988-year of high integrity container evaluation, controversy and regulatory action

International Nuclear Information System (INIS)

Jones, D.

1989-01-01

During 1988, the Nuclear Regulatory Commission(NRC) completed review of and prepared technical evaluation reports on several topical reports describing containers designed to meet the 10CFR61 requirements for high integrity containers (HICs). An all metal Ferralium container and a stainless steel/polyethylene lined container were approved by the NRC. However, the NRC did not approve any containers designed from polyethylene material. The NRC staff concluded that polyethylene containers do not meet the structural stability requirements of Part 61, and unless they are combined with some engineered structure or overpack, they are not adequate for disposal of low-level radioactive wastes that require disposal in a structurally stable form. In conflict with these NRC findings, the State of South Carolina Department of Health and Environmental Control (SCDHEC) has given interim approval for continued use of polyethylene containers at the Barnwell disposal site with some restrictions on how the containers are buried depending on the classification of the waste. This paper reviews the applicable federal regulations, presents a chronology of events describing how the controversy over high integrity containers evolved from 1980 to 1989, summarizes the technical issues involved and suggests an approach that waste generators should follow during this situation of regulatory uncertainty

77 FR 59679 - Central Vermont Public Service Corporation (Millstone Power Station, Unit 3); Order Approving...

Science.gov (United States)

2012-09-28

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0044; Docket No. 50-423] Central Vermont Public Service Corporation (Millstone Power Station, Unit 3); Order Approving Application Regarding Corporate Restructuring and Conforming Amendment I Dominion Nuclear Connecticut, Inc. (DNC), Central Vermont Public Service...

Strengthening of the nuclear safety regulatory body. Field evaluation review

International Nuclear Information System (INIS)

1996-10-01

As a result of a request from the Preparation Committee of the Nuclear Regulatory Authority (NRA) in 1992, and as recommended by the CEC/RAMG (Commission of European Communities/Regulatory Assistance Management Group) and the Agency mission in July 1993 to the Slovak Republic, the project SLR/9/005 was approved in 1993 as a model project for the period 1994-1996. Current budge is $401,340 and disbursements to date amount to $312,873. The project time schedule has been extended to 1997. The major conclusions of this evaluation are as follows: The project responded to an urgent national need, as well as to a statutory mandate of the Agency, and was adequately co-ordinated with other international assistance programmes to NRA. The project was designed as a structured programme of assistance by means of expert missions, scientific visits and a limited amount of equipment, acting upon several key areas of NRA regulatory responsibilities. Agency assistance was provided in a timely manner. A high concentration of expert missions was noticed at the initial stages of the project, which posed some managements problems. This was corrected to some extent in the course of implementation. Additionally, some overlapping of expert mission recommendations suggests that improvements are needed in the design of such missions. The exposure to international regulatory practice and expertise has resulted in substantial developments of NRA, both in organizational and operational terms. The project can claim to have contributed to NRA having gained governmental and international confidence. NRA's role in the safety assessment of Bohunice V1 reconstruction, as well as in Bohunice V2 safety review, Bohunice A1 decommissioning and in informing the public, also points at the success achieved by the project. The institutional and financial support of the Government contributed decisively to the project achievements. (author). Figs, tabs

Directory of Certificates of Compliance for radioactive materials packages: Report of NRC approved packages. Volume 1, Revision 18

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-10-01

The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance Number is included at the front of Volumes 1 and 2. An alphabetical listing by user name is included in the back of Volume 3 of approved QA programs. The reports include a listing of all users of each package design and approved QA programs prior to the publication date.

Directory of Certificates of Compliance for radioactive materials packages: Report of NRC approved packages. Volume 1, Revision 18

International Nuclear Information System (INIS)

1995-10-01

The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance Number is included at the front of Volumes 1 and 2. An alphabetical listing by user name is included in the back of Volume 3 of approved QA programs. The reports include a listing of all users of each package design and approved QA programs prior to the publication date

State regulatory issues in acid rain compliance

International Nuclear Information System (INIS)

Solomon, B.D.; Brick, S.

1992-01-01

This article discusses the results of a US EPA workshop for state regulators and commission staff on acid rain compliance concerns. The topics of the article include the results of market-based emissions control, how emissions trading is expected to reduce emissions, public utility commissions approval of compliance plans, the purposes of the workshop, market information, accounting issues, regulatory process and utility planning, multi-state compliance planning, and relationship to other compliance issues

Protection of third parties by collateral clauses of plan approvals or licenses

International Nuclear Information System (INIS)

Badura, P.

1989-01-01

This contribution discusses the regulatory functions of collateral clauses of plan approvals or licences, the legal protection of the constitutional and other rights of third parties in connection with the licensing of installations or similar projects, infringements of such rights and means of defence, and protection of neighbours under public law against noise. (RST) [de

Food irradiation—US regulatory considerations

Science.gov (United States)

Morehouse, Kim M.

2002-03-01

The use of ionizing radiation in food processing has received increased interest as a means of reducing the level of foodborne pathogens. This overview discusses the regulatory issues connected with the use of this technology in the United States. Several recent changes in the FDA's review process are discussed. These include the current policy that utilizes an expedited review process for petitions seeking approval of additives and technologies intended to reduce pathogen levels in food, and the recent USDA rule that eliminates the need for a separate rulemaking process by USDA for irradiation of meat and poultry. Recently promulgated rules and pending petitions before the FDA associated with the use of ionizing radiation for the treatment of foods are also discussed along with the current FDA labeling requirements for irradiated foods and the 1999 advanced notice of proposed rule on labeling. Another issue that is presented is the current status of the approval of packaging materials intended for food contact during irradiation treatment of foods.

Food irradiation--US regulatory considerations

International Nuclear Information System (INIS)

Morehouse, Kim M.

2002-01-01

The use of ionizing radiation in food processing has received increased interest as a means of reducing the level of foodborne pathogens. This overview discusses the regulatory issues connected with the use of this technology in the United States. Several recent changes in the FDA's review process are discussed. These include the current policy that utilizes an expedited review process for petitions seeking approval of additives and technologies intended to reduce pathogen levels in food, and the recent USDA rule that eliminates the need for a separate rulemaking process by USDA for irradiation of meat and poultry. Recently promulgated rules and pending petitions before the FDA associated with the use of ionizing radiation for the treatment of foods are also discussed along with the current FDA labeling requirements for irradiated foods and the 1999 advanced notice of proposed rule on labeling. Another issue that is presented is the current status of the approval of packaging materials intended for food contact during irradiation treatment of foods

Electronic Approval of Invoices (AEF)

CERN Multimedia

2003-01-01

With a view to the simplification of administrative procedures, AS and FI Divisions have drawn up a new procedure for the electronic approval of invoices via the EDH application. The aim of this new procedure is to rationalise the invoice approval process, notably by eliminating paper copies from the approval circuit. This will simplify the processing of invoices and facilitate their timely settlement, while at the same time maintaining a high level of security. This new procedure, in its current phase, will be gradually implemented from 1 November 2003 onwards. For clarification and further information, please see: http://ais.cern.ch/projs/AEF/help/help.htm . Finance Division, Accounts Payable Tel.: 7.22.95

Regulatory considerations for computational requirements for nuclear criticality safety

International Nuclear Information System (INIS)

Bidinger, G.H.

1995-01-01

As part of its safety mission, the U.S. Nuclear Regulatory Commission (NRC) approves the use of computational methods as part of the demonstration of nuclear criticality safety. While each NRC office has different criteria for accepting computational methods for nuclear criticality safety results, the Office of Nuclear Materials Safety and Safeguards (NMSS) approves the use of specific computational methods and methodologies for nuclear criticality safety analyses by specific companies (licensees or consultants). By contrast, the Office of Nuclear Reactor Regulation approves codes for general use. Historically, computational methods progressed from empirical methods to one-dimensional diffusion and discrete ordinates transport calculations and then to three-dimensional Monte Carlo transport calculations. With the advent of faster computational ability, three-dimensional diffusion and discrete ordinates transport calculations are gaining favor. With the proper user controls, NMSS has accepted any and all of these methods for demonstrations of nuclear criticality safety

75 FR 39932 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Science.gov (United States)

2010-07-13

...; Comment Request; Recognition Application for Sustainable Water Leadership Program (Renewal) AGENCY... Request (ICR) has been forwarded to the Office of Management and Budget (OMB) for review and approval... to: Office of Information and Regulatory Affairs, Office of Management and Budget (OMB), Attention...

76 FR 37867 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving...

Science.gov (United States)

2011-06-28

..., as Modified by Amendment No. 1, to Reduce the Minimum Size of the Nominating and Governance Committee... proposed rule change to reduce the minimum size of the Nominating and Governance Committee (``NGC'') from... the original proposed rule change, it had not yet obtained formal approval from its Board of Directors...

75 FR 41855 - Enogex L.L.C.; Notice of Petition for Rate Approval

Science.gov (United States)

2010-07-19

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-52-000] Enogex L.L.C.; Notice of Petition for Rate Approval July 13, 2010. Take notice that on July 1, 2010, Enogex L.L.C. (Enogex) filed pursuant to section 284.123(b)(2) of the Commission's regulations, filed a petition...

Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells.

Science.gov (United States)

Kanakry, Christopher G; Hess, Allan D; Gocke, Christopher D; Thoburn, Christopher; Kos, Ferdynand; Meyer, Christian; Briel, Janet; Luznik, Leo; Smith, B Douglas; Levitsky, Hyam; Karp, Judith E

2011-01-13

Few published studies characterize early lymphocyte recovery after intensive chemotherapy for acute myelogenous leukemia (AML). To test the hypothesis that lymphocyte recovery mirrors ontogeny, we characterized early lymphocyte recovery in 20 consecutive patients undergoing induction timed sequential chemotherapy for newly diagnosed AML. Recovering T lymphocytes were predominantly CD4(+) and included a greatly expanded population of CD3(+)CD4(+)CD25(+)Foxp3(+) T cells. Recovering CD3(+)CD4(+)CD25(+)Foxp3(+) T cells were phenotypically activated regulatory T cells and showed suppressive activity on cytokine production in a mixed lymphocyte reaction. Despite an initial burst of thymopoiesis, most recovering regulatory T cells were peripherally derived. Furthermore, regulatory T cells showed marked oligoclonal skewing, suggesting that their peripheral expansion was antigen-driven. Overall, lymphocyte recovery after chemotherapy differs from ontogeny, specifically identifying a peripherally expanded oligoclonal population of activated regulatory T lymphocytes. These differences suggest a stereotyped immunologic recovery shared by patients with newly diagnosed AML after induction timed sequential chemotherapy. Further insight into this oligoclonal regulatory T-cell population will be fundamental toward developing effective immunomodulatory techniques to improve survival for patients with AML.

Top-level regulatory criteria for the standard MHTGR

Energy Technology Data Exchange (ETDEWEB)

NONE

1986-10-15

The Licensing Plan for the Standard MHTGR (Ref. 1) describes a program to support a U.S. Nuclear Regulatory Commission (NRC) design review and approval. The Plan calls for the submittal of Top-Level Regulatory Criteria to the NRC for concurrence with their completeness and acceptability for the MHTGR program. The Top-Level Regulatory Criteria are defined as the standards for judging licensability that directly specify acceptable limits for protection of the public health and safety and the environment. The criteria proposed herein are for normal plant operation and a broad spectrum of anticipated events, including accidents. The approach taken is to define a set of criteria which are general as opposed to being design specific. Specifically, it is recommended that criteria be met which: 1. Are less prescriptive than current regulation, thereby encouraging maximum flexibility in design approaches. 2. Are measurable. 3. Are not more strict than the criteria for current power plants.

DNA residence time is a regulatory factor of transcription repression

Science.gov (United States)

Clauß, Karen; Popp, Achim P.; Schulze, Lena; Hettich, Johannes; Reisser, Matthias; Escoter Torres, Laura; Uhlenhaut, N. Henriette

2017-01-01

Abstract Transcription comprises a highly regulated sequence of intrinsically stochastic processes, resulting in bursts of transcription intermitted by quiescence. In transcription activation or repression, a transcription factor binds dynamically to DNA, with a residence time unique to each factor. Whether the DNA residence time is important in the transcription process is unclear. Here, we designed a series of transcription repressors differing in their DNA residence time by utilizing the modular DNA binding domain of transcription activator-like effectors (TALEs) and varying the number of nucleotide-recognizing repeat domains. We characterized the DNA residence times of our repressors in living cells using single molecule tracking. The residence times depended non-linearly on the number of repeat domains and differed by more than a factor of six. The factors provoked a residence time-dependent decrease in transcript level of the glucocorticoid receptor-activated gene SGK1. Down regulation of transcription was due to a lower burst frequency in the presence of long binding repressors and is in accordance with a model of competitive inhibition of endogenous activator binding. Our single molecule experiments reveal transcription factor DNA residence time as a regulatory factor controlling transcription repression and establish TALE-DNA binding domains as tools for the temporal dissection of transcription regulation. PMID:28977492

Directory of certificates of compliance for radioactive materials packages. Volume 1, Revision 17: Report of NRC approved packages

International Nuclear Information System (INIS)

1994-10-01

This directory contains a Report of NRC Approved Packages (Volume 1), Certificates of Compliance (Volume 2), and a Report of NRC Approved Quality Assurance Programs for Radioactive Materials Packages (Volume 3). The purpose of this directory is to make available a convenient source of information on Quality Assurance Programs and Packagings which have been approved by the US Nuclear Regulatory Commission. Shipments of radioactive material utilizing these packagings must be in accordance with the provisions of 49 CFR section 173.471 and 10 CFR Part 71, as applicable. In satisfying the requirements of Section 71.12, it is the responsibility of the licensees to insure themselves that they have a copy of the current approval and conduct their transportation activities in accordance with an NRC approved quality assurance program

76 FR 70331 - List of Approved Spent Fuel Storage Casks: MAGNASTOR ® System, Revision 2

Science.gov (United States)

2011-11-14

... Fuel Storage Casks: MAGNASTOR [supreg] System, Revision 2 AGENCY: Nuclear Regulatory Commission. ACTION... its spent fuel storage regulations by revising the NAC International, Inc. (NAC) MAGNASTOR [supreg] System listing within the ``List of Approved Spent Fuel Storage Casks'' to include Amendment No. 2 to...

76 FR 2277 - List of Approved Spent Fuel Storage Casks: NUHOMS® HD System Revision 1

Science.gov (United States)

2011-01-13

... Fuel Storage Casks: NUHOMS[supreg] HD System Revision 1 AGENCY: Nuclear Regulatory Commission. ACTION... System listing within the ``List of Approved Spent Fuel Storage Casks'' to include Amendment No. 1 to... the NUHOMS[supreg] HD Horizontal Modular Storage System for Irradiated Nuclear Fuel. [[Page 2279...

Safety Evaluation Report related to the final design approval of the GESSAR II BWR/6 Nuclear Island design, Docket No. 50-447

International Nuclear Information System (INIS)

1983-04-01

The Safety Evaluation Report for the application filed by General Electric Company for the Final Design Approval for the General Electric Standard Safety Analysis Report (GESSAR II FSAR) has been prepared by the Office of Nuclear Reactor Regulation of the Nuclear Regulatory Commission. This report summarizes the results of the staff's safety review of the GESSAR II BWR/6 Nuclear Island Design. Subject to favorable resolution of items discussed in the Safety Evaluation Report, the staff concludes that the facilities referencing GESSAR II, subject to approval of the balance-of-plant design, can conform with the provisions of the Act and the regulations of the Nuclear Regulatory Commission

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

Science.gov (United States)

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

2014-01-01

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

75 FR 26827 - Self-Regulatory Organizations; Order Approving Minor Rule Violation Plan for EDGA Exchange, Inc.

Science.gov (United States)

2010-05-12

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62037; File No. 4-595] Self-Regulatory... Commission adopted amendments to paragraph (c) of Rule 19d-1 to allow self-regulatory organizations (``SROs... would not be subject to the provisions of Rule 19d-1(c)(1) under the Act\\4\\ requiring that a self...

75 FR 26822 - Self-Regulatory Organizations; Order Approving Minor Rule Violation Plan for EDGX Exchange, Inc.

Science.gov (United States)

2010-05-12

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62036; File No. 4-594] Self-Regulatory... Commission adopted amendments to paragraph (c) of Rule 19d-1 to allow self-regulatory organizations (``SROs... would not be subject to the provisions of Rule 19d-1(c)(1) under the Act \\4\\ requiring that a self...

Anti-infective medicine quality: analysis of basic product quality by approval status and country of manufacture

Directory of Open Access Journals (Sweden)

Bate R

2012-07-01

Full Text Available Roger Bate,1 Lorraine Mooney,2 Kimberly Hess,3 Julissa Milligan,1 Amir Attaran41American Enterprise Institute, Washington DC, USA; 2Africa Fighting Malaria, London, UK; 3Africa Fighting Malaria, Washington DC, USA; 4Faculty of Law and Medicine, University of Ottawa, Ottawa, CanadaBackground: Some medicines for sale in developing countries are approved by a stringent regulatory authority (SRA or the World Health Organization (WHO prequalification program; many of these are global brands. This study ascertains whether medicines approved by SRAs or the WHO perform better in simple quality tests than those that have not been approved by either.Methods: Over the past 4 years, 2652 essential drugs (products to treat malaria, tuberculosis, and bacterial infections were procured by covert shoppers from eleven African cities and eight cities in a variety of mid-income nations. All samples were assessed using the Global Pharma Health Fund eV Minilab® protocol to identify whether they were substandard, degraded, or counterfeit.Results: The failure rate among SRA-approved products was 1.01%, among WHO-approved products was 6.80%, and 13.01% among products that were not approved by either. African cities had a greater proportion of SRA- or WHO-approved products (31.50% than Indian cities (26.57%, but they also experienced a higher failure rate (14.21% than Indian cities (7.83%. The remainder of cities tested had both the highest proportion of approved products at 34.46% and the lowest failure rate at 2.70%. Products made in Africa had the highest failure rate at 25.77%, followed by Chinese products at 15.74%, Indian products at 3.70%, and European/US products, which failed least often, at 1.70%. Most worrying is that 17.65% of Chinese products approved by the WHO failed.Conclusion: The results strongly indicate that approval by either an SRA or the WHO is correlated with higher medicine quality at a statistically significant level. The comparatively high

The European Regulatory Environment of RNA-Based Vaccines.

Science.gov (United States)

Hinz, Thomas; Kallen, Kajo; Britten, Cedrik M; Flamion, Bruno; Granzer, Ulrich; Hoos, Axel; Huber, Christoph; Khleif, Samir; Kreiter, Sebastian; Rammensee, Hans-Georg; Sahin, Ugur; Singh-Jasuja, Harpreet; Türeci, Özlem; Kalinke, Ulrich

2017-01-01

A variety of different mRNA-based drugs are currently in development. This became possible, since major breakthroughs in RNA research during the last decades allowed impressive improvements of translation, stability and delivery of mRNA. This article focuses on antigen-encoding RNA-based vaccines that are either directed against tumors or pathogens. mRNA-encoded vaccines are developed both for preventive or therapeutic purposes. Most mRNA-based vaccines are directly administered to patients. Alternatively, primary autologous cells from cancer patients are modified ex vivo by the use of mRNA and then are adoptively transferred to patients. In the EU no regulatory guidelines presently exist that specifically address mRNA-based vaccines. The existing regulatory framework, however, clearly defines that mRNA-based vaccines in most cases have to be centrally approved. Interestingly, depending on whether RNA-based vaccines are directed against tumors or infectious disease, they are formally considered gene therapy products or not, respectively. Besides an overview on the current clinical use of mRNA vaccines in various therapeutic areas a detailed discussion of the current regulatory situation is provided and regulatory perspectives are discussed.

Directory of certificates of compliance for radioactive materials packages. Summary report of NRC approved packages

International Nuclear Information System (INIS)

1979-10-01

This directory contains a Summary Report of NRC Approved Packages for radioactive material packages effective September 14, 1979. Purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance number is included at the back of each volume of the directory. The Summary Report includes a listing of all users of each package design prior to the publication date of the directory

Directory of certificates of compliance for radioactive materials packages. Summary report of NRC approved packages

Energy Technology Data Exchange (ETDEWEB)

None

1979-10-01

This directory contains a Summary Report of NRC Approved Packages for radioactive material packages effective September 14, 1979. Purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance number is included at the back of each volume of the directory. The Summary Report includes a listing of all users of each package design prior to the publication date of the directory.

78 FR 78693 - List of Approved Spent Fuel Storage Casks: Transnuclear, Inc. Standardized NUHOMS® Cask System

Science.gov (United States)

2013-12-27

... Storage Casks: Transnuclear, Inc. Standardized NUHOMS[supreg] Cask System AGENCY: Nuclear Regulatory... storage regulations by revising the Transnuclear, Inc. Standardized NUHOMS[supreg] Cask System listing within the ``List of Approved Spent Fuel Storage Casks'' to include Amendment No. 11 to Certificate of...

77 FR 24585 - List of Approved Spent Fuel Storage Casks: HI-STORM 100, Revision 8

Science.gov (United States)

2012-04-25

... Storage Casks: HI-STORM 100, Revision 8 AGENCY: Nuclear Regulatory Commission. ACTION: Direct final rule... revising the Holtec International HI-STORM 100 System listing within the ``List of Approved Spent Fuel...) 72.214, by revising the Holtec International HI-STORM 100 System listing within the ``List of...

75 FR 24786 - List of Approved Spent Fuel Storage Casks: NUHOMS® HD System Revision 1

Science.gov (United States)

2010-05-06

... Fuel Storage Casks: NUHOMS[supreg] HD System Revision 1 AGENCY: Nuclear Regulatory Commission. ACTION... storage regulations by revising the Transnuclear, Inc. (TN) NUHOMS[supreg] HD System listing within the... System cask design within the list of approved spent fuel storage casks that power reactor licensees can...

78 FR 22020 - Agency Information Collection Activities: Requests for Comments; Clearance of New Approval of...

Science.gov (United States)

2013-04-12

... about our intention to request the Office of Management and Budget (OMB) approval for a new information... will define what a propeller critical part is, require the identification of propeller critical parts... information collection to the Office of Information and Regulatory Affairs, Office of Management and Budget...

76 FR 46322 - Agency Information Collection Activities Under OMB Review; Renewal of a Currently Approved...

Science.gov (United States)

2011-08-02

... has forwarded the following Information Collection Request (ICR) to the Office of Management and Budget (OMB) for review and approval: Recreation Visitor Use Surveys. The ICR describes the nature of the... Department of the Interior at the Office of Management and Budget, Office of Information and Regulatory...

76 FR 13442 - Joint Industry Plan; Order Approving Amendment No. 25 to the Joint Self-Regulatory Organization...

Science.gov (United States)

2011-03-11

..., Consolidation and Dissemination of Quotation and Transaction Information for Nasdaq-Listed Securities Traded on... Exchange, Inc., Financial Industry Regulatory Authority, Inc., International Securities Exchange LLC...-Regulatory Organization Plan Governing the Collection, Consolidation, and Dissemination of Quotation and...

78 FR 66788 - Joint Industry Plan; Order Approving Amendment No. 30 to the Joint Self-Regulatory Organization...

Science.gov (United States)

2013-11-06

..., Consolidation and Dissemination of Quotation and Transaction Information for Nasdaq-Listed Securities Traded on... Exchange, Inc., Financial Industry Regulatory Authority, Inc., International Securities Exchange LLC...-Regulatory Organization Plan Governing the Collection, Consolidation, and Dissemination of Quotation and...

Revised guideline for the approval procedure of package designs in Germany

International Nuclear Information System (INIS)

Nitsche, F.; Roedel, R.

2004-01-01

The IAEA Regulations for the Safe Transport of Radioactive Material, TS-R-1 are applied in Germany through the implementation of the Dangerous Goods Transport Regulations for class 7 of the International Modal Organisations (ADR, RID, IMDG-Code, ICAO-TI). Based on this the approval procedures for packages designs applied in Germany are in compliance with the provisions of TS-R-1. The Guideline R 003 issued by the Ministry of Transport, Building and Housing (BMVBW) in 1991 is the basis for the package design approval procedures in Germany. This Guideline has been reviewed and revised to reflect latest developments in the regulations as well as in the regulatory practice. In particular it has been extended to the approval procedures of Type C packages, packages subject to transitional arrangements, special form and low dispersible radioactive material and provides more detailed information to the applicant about the requested documentation. Publication of this revised guideline has been delayed but it is expected to take place in October 2004. The paper gives an overview about the main parts and provisions of this revised Guideline R 003 with the focus on package design approval procedures

Directory of Certificates of Compliance for Radioactive Materials Packages. Summary report of NRC approved packages. Volume 1, Revision 8

International Nuclear Information System (INIS)

1985-10-01

This directory contains a Summary Report of NRC Approved Packages (Volume 1), Certificates of Compliance (Volume 2), and a Summary Report of NRC Approved Quality Assurance Programs for Radioactive Material Packages (Volume 3). The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance number is included at the back of each volume of the directory. The Summary Report includes a listing of all users of each package design prior to the publication date of the directory. Shipments of radioactive material utilizing these packagings must be in accordance with the provisions of 49 CFR 173.471 and 10 CFR Part 71, as applicable. In satisfying the requirements of Section 71.12, it is the responsibility of the licensees to insure them that they have a copy of the current approval and conduct their transportation activities in accordance with an NRC approved quality assurance program. Copies of the current approval may be obtained from the US Nuclear Regulatory Commission Public Document Room files (see Docket No. listed on each certificate) at 1717 H Street, Washington, DC 20555. Note that the general license of 10 CFR 71.12 does not authorize the receipt, possession, use or transfer of byproduct source, or special nuclear material; such authorization must be obtained pursuant to 10 CFR Parts 30 to 36, 40, 50, or 70

Directory of certificates of compliance for radioactive materials packages. Summary report of NRC approved packages. Volume 1. Revision 9

International Nuclear Information System (INIS)

1986-10-01

This directory contains a Summary Report of NRC Approved Packages (Volume 1), Certificates of Compliance (Volume 2), and a Summary Report of NRC Approved Quality Assurance Programs for Radioactive Material Packages (Volume 3). The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and Corresponding Certificate of Compliance number is included at the back of each volume of the directory. The Summary Report includes a listing of all users of each package design prior to the publication date of the directory. Shipments of radioactive material utilizing these packagings must be in accordance with the provisions of 49 CFR 173.471 and 10 CFR Part 71, as applicable. In satisfying the requirements of Sections 71.12, it is the responsibility of the licensees to insure them that they have a copy of the current approval and conduct their transportation activities in accordance with an NRC approved quality assurance program. Copies of the current approval may be obtained from the US Nuclear Regulatory Commission Public Document Room files (see Docket No. listed on each certificate) at 1717 H Street, Washington, DC 20555. Note that the general license of 10 CFR 71.12 does not authorize the receipt, possession, use or transfer of byproduct source, or special nuclear material; such authorization must be obtained pursuant to 10 CFR Parts 30 to 36, 40, 50, or 70

Directory of certificates of compliance for radioactive materials packages. Summary report of NRC approved packages. Volume 1, Revision 7

International Nuclear Information System (INIS)

1984-11-01

This directory contains a Summary Report of NRC Approved Packages (Volume 1), Certificates of Compliance (Volume 2), and a Summary Report of NRC Approved Quality Assurance Programs for Radioactive Material Packages (Volume 3). The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance number is included at the back of each volume of the directory. The Summary Report includes a listing of all users of each package design prior to the publication date of the directory. Shipments of radioactive material utilizing these packagings must be in accordance with the provisions of 49 CFR 173.471 and 10 CFR Part 71, as applicable. In satisfying the requirements of Section 71.12, it is the responsibility of the licensees to insure that they have a copy of the current approval and conduct their transportation activities in accordance with an NRC approved quality assurance program. Copies of the current approval may be obtained from the US Nuclear Regulatory Commission Public Document Room files (see Docket No. listed on each certificate) at 1717 H Street, Washington, DC 20555. Note that the general license of 10 CFR 71.12 does not authorize the receipt, possession, use or transfer of byproduct source, or special nuclear material; such authorization must be obtained pursuant to 10 CFR Parts 30 to 36, 40, 50, or 70

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

Science.gov (United States)

2011-08-17

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

77 FR 61033 - Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed...

Science.gov (United States)

2012-10-05

...) NSCC's automated ACATS-Fund/SERV interface, for eligible mutual fund assets; (iii) NSCC's ACATS-IPS... customer account asset data. \\4\\ ACATS complements Financial Industry Regulatory Authority (``FINRA'') Rule... positions and available securities are allocated by book entry. This allocation of securities is...

Time-dependent sorption of two novel fungicides in soils within a regulatory framework.

Science.gov (United States)

Gulkowska, Anna; Buerge, Ignaz J; Poiger, Thomas; Kasteel, Roy

2016-12-01

Convincing experimental evidence suggests increased sorption of pesticides on soil over time, which, so far, has not been considered in the regulatory assessment of leaching to groundwater. Recently, Beulke and van Beinum (2012) proposed a guidance on how to conduct, analyse and use time-dependent sorption studies in pesticide registration. The applicability of the recommended experimental set-up and fitting procedure was examined for two fungicides, penflufen and fluxapyroxad, in four soils during a 170 day incubation experiment. The apparent distribution coefficient increased by a factor of 2.5-4.5 for penflufen and by a factor of 2.5-2.8 for fluxapyroxad. The recommended two-site, one-rate sorption model adequately described measurements of total mass and liquid phase concentration in the calcium chloride suspension and the calculated apparent distribution coefficient, passing all prescribed quality criteria for model fit and parameter reliability. The guidance is technically mature regarding the experimental set-up and parameterisation of the sorption model for the two moderately mobile and relatively persistent fungicides under investigation. These parameters can be used for transport modelling in soil, thereby recognising the existence of the experimentally observed, but in the regulatory leaching assessment of pesticides not yet routinely considered phenomenon of time-dependent sorption. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Value Assessment in the Regulatory Context.

Science.gov (United States)

Miller, Kathleen L; Woodcock, Janet

2017-02-01

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

A Kalman-filter based approach to identification of time-varying gene regulatory networks.

Directory of Open Access Journals (Sweden)

Jie Xiong

Full Text Available MOTIVATION: Conventional identification methods for gene regulatory networks (GRNs have overwhelmingly adopted static topology models, which remains unchanged over time to represent the underlying molecular interactions of a biological system. However, GRNs are dynamic in response to physiological and environmental changes. Although there is a rich literature in modeling static or temporally invariant networks, how to systematically recover these temporally changing networks remains a major and significant pressing challenge. The purpose of this study is to suggest a two-step strategy that recovers time-varying GRNs. RESULTS: It is suggested in this paper to utilize a switching auto-regressive model to describe the dynamics of time-varying GRNs, and a two-step strategy is proposed to recover the structure of time-varying GRNs. In the first step, the change points are detected by a Kalman-filter based method. The observed time series are divided into several segments using these detection results; and each time series segment belonging to two successive demarcating change points is associated with an individual static regulatory network. In the second step, conditional network structure identification methods are used to reconstruct the topology for each time interval. This two-step strategy efficiently decouples the change point detection problem and the topology inference problem. Simulation results show that the proposed strategy can detect the change points precisely and recover each individual topology structure effectively. Moreover, computation results with the developmental data of Drosophila Melanogaster show that the proposed change point detection procedure is also able to work effectively in real world applications and the change point estimation accuracy exceeds other existing approaches, which means the suggested strategy may also be helpful in solving actual GRN reconstruction problem.

76 FR 44583 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Science.gov (United States)

2011-07-26

... designated method are manufactured in an ISO 9001-registered facility. Also, an applicant must submit a minor... of Management and Budget (OMB) for review and approval. This is a request to renew an existing... and Regulatory Affairs, Office of Management and Budget (OMB), Attention: Desk Officer for EPA, 725...

75 FR 5786 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Science.gov (United States)

2010-02-04

... Activities; Submission to OMB for Review and Approval; Comment Request; NSPS for Steel Plants: Electric Arc... [email protected] , or by mail to: EPA Docket Center (EPA/DC), Environmental Protection Agency...., Washington, DC 20460, and (2) OMB at: Office of Information and Regulatory Affairs, Office of Management and...

Analysis of the Education Program Approval Process: A Program Evaluation.

Science.gov (United States)

Fountaine, Charles A.; And Others

A study of the education program approval process involving the Veterans Administration (VA) and the State Approving Agencies (SAAs) had the following objectives: to describe the present education program approval process; to determine time and costs associated with the education program approval process; to describe the approval process at…

Development Perspective of Regulatory Audit Code System for SFR Nuclear Safety Evaluation

Energy Technology Data Exchange (ETDEWEB)

Bae, Moo Hoon; Lee, Gil Soo; Shin, An Dong; Suh, Nam Duk [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2012-05-15

A sodium-cooled fast reactor (SFR) in Korea is based on the KALIMER-600 concept developed by KAERI. Based on 'Long-term R and D Plan for Future Reactor Systems' which was approved by the Korea Atomic Energy Commission in 2008, the KAERI designer is scheduled to apply the design certification of the prototype SFR in 2017. In order to establish regulatory infrastructure for the licensing of a prototype SFR, KINS has develop the regulatory requirements for the demonstration SFR since 2010, and are scheduled to develop the regulatory audit code systems in regard to core, fuel, and system, etc. since 2012. In this study, the domestic code systems used for core design and safety evaluation of PWRs and the nuclear physics and code system for SFRs were briefly reviewed, and the development perspective of regulatory audit code system for SFR nuclear safety evaluation were derived

Respirator studies for the Nuclear Regulatory Commission. Protection factors for supplied-air respirators. Progress report, October 1, 1976--September 30, 1977

International Nuclear Information System (INIS)

Hack, A.; Bradley, O.D.; Trujillo, A.

1977-12-01

This report describes the work performed during FY 1977 for the Nuclear Regulatory Commission. The Protection Factors (efficiency) provided by 25 NIOSH approved supplied-air respirators were determined while the devices were worn by a panel of anthropometrically selected test subjects. The major recommendation was that demand-type respirators should neither be used nor approved

77 FR 26016 - Determination of Regulatory Review Period for Purposes of Patent Extension; Alair Bronchial...

Science.gov (United States)

2012-05-02

... approval phase starts with the initial submission of an application to market the device and continues until permission to market the device is granted. Although only a portion of a regulatory review period... asthma is not well controlled [[Page 26017

Directory of certificates of compliance for radioactive materials packages; Summary Report of NRC Approved Packages

International Nuclear Information System (INIS)

1980-12-01

This directory contains a Summary Report of NRC approved Packages (Volume 1), Certificates of Compliance (Volume 2), and a Summary Report of NRC Approved Quality Assurance Programs for Radioactive Material Packages (Volume 3). The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the U.S. Nuclear Regulatory Commission. To assist in identifying packaging, and index by Model Number and corresponding Certificate of Compliance number is included at the back of each volume of the directory. The Summary Report includes a listing of all users of each package design prior to the publication date of the directory. Shipments of radioactive material using these packagings must be in accordance with the provisions of 49 CFR 173.393a and 10 CFR Part 71, as applicable. In satisfying the requirements of Section 71.12, it is the responsibility of the licensees to insure them--that they have a copy of the current approval and conduct their transportation activities in accordance with an NRC approved quality assurance program

76 FR 2243 - List of Approved Spent Fuel Storage Casks: NUHOMS ® HD System Revision 1

Science.gov (United States)

2011-01-13

... Storage Casks: NUHOMS [supreg] HD System Revision 1 AGENCY: Nuclear Regulatory Commission. ACTION: Direct... fuel storage regulations by revising the Transnuclear, Inc. (TN) NUHOMS [supreg] HD System listing... NUHOMS [supreg] HD System cask design listed in Sec. 72.214 (List of approved spent fuel storage casks...

Approval plans issues and innovations

CERN Document Server

Katz, Linda S

2013-01-01

How can you, as an acquisition librarians, keep current on the output of hundreds of publishers? The answer, of course, is that you cannot. For over 30 years, approval plans have been used by librarians to acquire current titles, save staff time, and build core collections. Even today, these reasons seem appropriate, as libraries try to maintain up-to-date collections and control personnel and operating budgets. However, as shown in Approval Plans: Issues and Innovations, the use of approval plans is not so simple and straightforward; their use is subject to complex procedures and policies--an

75 FR 82119 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

Science.gov (United States)

2010-12-29

..., the Board's basic fair practice rule, to apply the rules to municipal advisors. The proposed rule... Independent Public Finance Advisors, dated December 9, 2010. This order approves the proposed rule change. II... of which may have a substantial impact on the finances of those municipal entities. In other cases...

77 FR 75243 - Self-Regulatory Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change...

Science.gov (United States)

2012-12-19

... modeling and risk management procedures (``Risk Management Proposal'') \\9\\ is approved by the Commission... risk modeling enhancements with respect to longer-tenor options, including OTC S&P 500 Index Options... http://www.sec.gov/rules/petitions/2012/petn4-644.pdf . This Order does not address the relief...

Directory of Certificates of Compliance for Radioactive Materials Packages: Report of NRC Approved Quality Assurance Programs for Radioactive Materials Packages

International Nuclear Information System (INIS)

1993-10-01

This directory contains a Report of NRC Approved Packages (Volume 1), Certificates of Compliance (Volume 2), and a Report of NRC Approved Quality Assurance Programs for Radioactive Materials Packages (Volume 3). The purpose of this directory is to make available a convenient source of information on Quality Assurance Programs and Packagings which have been approved by the US Nuclear Regulatory Commission. Shipments of radioactive material utilizing these packagings must be in accordance with the provisions of 49 CFR section 173.471 and 10 CFR Part 71, as applicable. In satisfying the requirements of Section 71.12, it is the responsibility of the licensees to insure themselves that they have a copy of the current approval and conduct their transportation activities in accordance with an NRC approved quality assurance program

Integrating external biological knowledge in the construction of regulatory networks from time-series expression data

Directory of Open Access Journals (Sweden)

Lo Kenneth

2012-08-01

Full Text Available Abstract Background Inference about regulatory networks from high-throughput genomics data is of great interest in systems biology. We present a Bayesian approach to infer gene regulatory networks from time series expression data by integrating various types of biological knowledge. Results We formulate network construction as a series of variable selection problems and use linear regression to model the data. Our method summarizes additional data sources with an informative prior probability distribution over candidate regression models. We extend the Bayesian model averaging (BMA variable selection method to select regulators in the regression framework. We summarize the external biological knowledge by an informative prior probability distribution over the candidate regression models. Conclusions We demonstrate our method on simulated data and a set of time-series microarray experiments measuring the effect of a drug perturbation on gene expression levels, and show that it outperforms leading regression-based methods in the literature.

76 FR 5417 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

Science.gov (United States)

2011-01-31

... consisting of amendments to Rule A-3, on membership on the Board, in order to establish a Nominating... Independent Public Finance Advisors to discuss the proposed rule change among other matters. See Memorandum... to the creation of the Nominating Committee of the MSRB. On September 30, 2010, the SEC approved MSRB...

76 FR 19173 - Self-Regulatory Organizations; the Options Clearing Corporation; Order Granting Approval of...

Science.gov (United States)

2011-04-06

... to list and trade options on the CBOE Gold ETF Volatility Index.\\6\\ The March 2011 Supplement amends... on the CBOE Gold ETF Volatility Index and similarly structured equity-based volatility indexes that...) (order approving CBOE's proposed rules to list and trade CBOE Gold ETF Volatility Index options). \\7\\ For...

78 FR 24257 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

Science.gov (United States)

2013-04-24

... positions are in-the- money or out-of-the-money. Volume, like open interest, is a measure of a Clearing... demands on OCC's services and facilities that are not captured by the current methodology. IV. Conclusion... Organizations; The Options Clearing Corporation; Order Approving Proposed Rule Change To Implement a Revised...

RESEARCH Analysis of time to regulatory and ethical approval of ...

African Journals Online (AJOL)

against TB.5-7 As a result of this work, the SATVI clinical research site in Worcester, Western ... TB vaccine in 2004 were included in this analysis. ..... Bollyky TJ, Cockburn IM, Berndt E. Bridging the gap: improving clinical development and the.

A flexible regulatory framework

International Nuclear Information System (INIS)

Silvennoinen, T.

2000-01-01

Regulatory reform of the Finnish electricity market meant opening up potentially competitive parts of the electricity sector to competition and eliminating all unnecessary forms of regulation covering generation, wholesale supply, retail supply, and foreign trade in electricity. New types of control and regulatory mechanisms and institutions were set up for those parts of the electricity industry that were excluded from competition, such as network operations. Network activities now have to be licensed, whereas no licence is needed for generation or supply. A new sector-specific regulatory authority was established in 1995 to coincide with the implementation of the Electricity Market Act, known as the Electricity Market Authority. This is responsible for regulating network activities and retail supply to captive customers. The core function of the authority, which employs some 14 people, is to promote the smooth operation of the Finnish electricity market and to oversee the implementation of the Electricity Market Act and its provisions. Its most important duties are linked to overseeing the process by which network companies price their electricity. As price regulation no longer exists, all the companies in the electricity sector set their tariffs independently, even network companies. The job of controlling the pricing of network services is handed by the Electricity Market Authority, following the principles of competition control. Pricing control takes place ex post - after a pricing system has been adopted by a company and concentrates on individual cases and companies. There is no ex ante system of setting or approving prices and tariffs by the regulator. The tariffs and pricing of network services can be evaluated, however, by both the Electricity Market Authority and the Finnish Competition Authority, which have overlapping powers as regards the pricing of network activities. The Finnish regulatory framework can be described as a system of light

Overcoming regulatory and economic challenges facing pharmacogenomics.

Science.gov (United States)

Cohen, Joshua P

2012-09-15

The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist. From a regulatory perspective, therapeutics and companion diagnostics are ideally developed simultaneously, with the clinical significance of the diagnostic established using data from the clinical development program of the corresponding therapeutic. Nevertheless, this is not (yet) happening. Most personalized medicines are personalized post hoc, that is, a companion diagnostic is developed separately and approved after the therapeutic. This is due in part to a separate and more complex regulatory process for diagnostics coupled with a lack of clear regulatory guidance. More importantly, payers have placed restrictions on reimbursement of personalized medicines and their companion diagnostics, given the lack of evidence on the clinical utility of many tests. To achieve increased clinical adoption of diagnostics and targeted therapies through more favorable reimbursement and incorporation in clinical practice guidelines, regulators will need to provide unambiguous guidance and manufacturers will need to bring more and better clinical evidence to the market place. Copyright © 2012 Elsevier B.V. All rights reserved.

76 FR 33121 - List of Approved Spent Fuel Storage Casks: HI-STORM Flood/Wind Addition

Science.gov (United States)

2011-06-08

... Storage Casks: HI-STORM Flood/Wind Addition AGENCY: Nuclear Regulatory Commission. ACTION: Direct final... regulations to add the Holtec HI-STORM Flood/Wind cask system to the ``List of Approved Spent Fuel Storage... Title 10 of the Code of Federal Regulations Section 72.214 to add the Holtec HI- STORM Flood/Wind cask...

77 FR 28375 - Eagle Rock Desoto Pipeline, L.P.; Notice of Petition for Rate Approval

Science.gov (United States)

2012-05-14

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR12-25-000] Eagle Rock Desoto Pipeline, L.P.; Notice of Petition for Rate Approval Take notice that on May 1, 2012, Eagle Rock Desoto Pipeline, L.P. (Desoto) filed a Rate Election pursuant to 284.123(b)(1) of the Commissions...

76 FR 30832 - Approval and Promulgation of Air Quality Implementation Plans; West Virginia; Permits for...

Science.gov (United States)

2011-05-27

... not a ``significant regulatory action'' subject to review by the Office of Management and Budget under... 0 2. In Sec. 52.2520, the table in paragraph (c) is amended by revising the entries for [45 CSR.../subject effective EPA approval date explanation/citation 45 CSR] date at 40 CFR 52.2565 * * * * * * * [45...

76 FR 38601 - Notice of Request for Extension of Approval of an Information Collection; Self-Certification...

Science.gov (United States)

2011-07-01

... approval of an information collection. Abstract: The Marketing and Regulatory Programs (MRP) agencies of.... agricultural products and protect the health of domestic animal and plant resources. The MRP agencies are the... human resource management, for the three MRP agencies are provided by the MRP Business Services unit of...

Adolescents’ and Parents’ Regulatory Focus as Determinants of Future Time Perspective on School and Professional Career

NARCIS (Netherlands)

Andre, L.; van Vianen, A.E.M.; Peetsma, T.T.D.

2017-01-01

Future time perspective (FTP) - individuals' orientation towards future goals and consideration of future consequences - is a successful motivator in education and work. This study is the first that integrates Regulatory focus (RF) theory with FTP theory to explore relationships between adolescents'

What to Know About Medicines With New Active Ingredients Approved in FY 2016 / 2016 in Japan and EU: A Brief Comparison of New Medicines Approved in Japan and the EU in 2016.

Science.gov (United States)

Kondo, Hideyuki; Saint-Raymond, Agnès; Yasuda, Naoyuki

2018-03-01

The Pharmaceuticals and Medical Devices Agency (PMDA) in Japan and the European Medicines Agency (EMA) have a long-standing experience of reviews of new medicines, and they meet their target pre-market review periods. In FY 2016 / 2016, 112 and 83 new medicines were approved in Japan and EU, respectively. Out of these medicines, 41 and 27 medicines containing new active ingredients were approved with total pre-market review periods of 209 days and 428 days in Japan and EU, respectively. Approximately one-third of these medicines were reviewed by the Agencies in close timing, within 1 year between pre-market review applications in Japan and in EU. Taking into account the increasing number of global clinical trials and constant number of consultations or scientific advice related to global clinical trials in Japan, it is clear that the importance of the continuous, collaborative relationship between EMA and PMDA is more and more crucial, as it does facilitate close and timely exchange of information and opinions on products and technologies under development. There already are effective collaborative frameworks between PMDA and EMA in addition to daily communication, and our findings support the development and best use of regulatory tools such as consultation services and scientific advice/protocol assistance for the benefit of the pharmaceutical industry but mostly of patients.

75 FR 25010 - Self-Regulatory Organizations; Stock Clearing Corporation of Philadelphia; Notice of Filing and...

Science.gov (United States)

2010-05-06

...-025, The NASDAQ Stock Market LLC (``NASDAQ Exchange'') sought and received Commission approval to... requirements apply to elections of directors and were not amended. Each share of common stock has one vote,\\8...-Regulatory Organizations; Stock Clearing Corporation of Philadelphia; Notice of Filing and Immediate...

Evaluation of artificial time series microarray data for dynamic gene regulatory network inference.

Science.gov (United States)

Xenitidis, P; Seimenis, I; Kakolyris, S; Adamopoulos, A

2017-08-07

High-throughput technology like microarrays is widely used in the inference of gene regulatory networks (GRNs). We focused on time series data since we are interested in the dynamics of GRNs and the identification of dynamic networks. We evaluated the amount of information that exists in artificial time series microarray data and the ability of an inference process to produce accurate models based on them. We used dynamic artificial gene regulatory networks in order to create artificial microarray data. Key features that characterize microarray data such as the time separation of directly triggered genes, the percentage of directly triggered genes and the triggering function type were altered in order to reveal the limits that are imposed by the nature of microarray data on the inference process. We examined the effect of various factors on the inference performance such as the network size, the presence of noise in microarray data, and the network sparseness. We used a system theory approach and examined the relationship between the pole placement of the inferred system and the inference performance. We examined the relationship between the inference performance in the time domain and the true system parameter identification. Simulation results indicated that time separation and the percentage of directly triggered genes are crucial factors. Also, network sparseness, the triggering function type and noise in input data affect the inference performance. When two factors were simultaneously varied, it was found that variation of one parameter significantly affects the dynamic response of the other. Crucial factors were also examined using a real GRN and acquired results confirmed simulation findings with artificial data. Different initial conditions were also used as an alternative triggering approach. Relevant results confirmed that the number of datasets constitutes the most significant parameter with regard to the inference performance. Copyright © 2017 Elsevier

76 FR 15322 - Determination of Regulatory Review Period for Purposes of Patent Extension; VPRIV

Science.gov (United States)

2011-03-21

..., medical device, food additive, or color additive) was subject to regulatory review by FDA before the item... therapy for pediatric and adult patients with type 1 Gaucher Disease. Subsequent to this approval, the...,138,262) from Shire Human Genetic Therapies, Inc., and the Patent and Trademark Office requested FDA's...

78 FR 41846 - Approval and Promulgation of Implementation Plans; New York State Ozone Implementation Plan Revision

Science.gov (United States)

2013-07-12

... Pavement and Asphalt Based Surface Coating,'' (see 77 FR 13974). It is important to note that EPA is... approved regulations'' in 40 CFR 52.1670 for the Part 241, ``Asphalt Pavement and Asphalt Based Surface..., this action: Is not a ``significant regulatory action'' subject to review by the Office of Management...

Regulatory compliance issues related to the White Oak Creek Embayment time-critical removal action

International Nuclear Information System (INIS)

Leslie, M.; Kimmel, B.L.

1992-01-01

In September 1990, Martin Marietta Energy Systems (Energy Systems) discovered high levels of Cesium-137 present in surface sediments at the mouth of White Oak Creek (WOC) Embayment. WOC receives the majority of surface water drainage from Oak Ridge National Laboratory. Following this discovery, the Department of Energy (DOE) and Energy Systems pursued stabilizing sediment migration under provisions of the National Contingency Plan (NCP) Section 300.400 et. seq. as a time-critical removal action. However, significant uncertainty exists concerning the applicability of NCP procedural requirements designed for conducting US EPA-led, Superfund-financed response actions, because NCP Subpart K dealing with response actions at federal facilities has not been promulgated. In addition, relatively new guidance exists from DOE concerning National Environmental Policy Act documentation requirements for categorical exclusions associated with conducting removal actions at DOE facilities. A proactive approach was taken to identify issues and involve appropriate state and federal regulatory agencies. This approach required achieving consensus among all involved parties and identification of all applicable or relevant and appropriate regulatory requirements related to the removal action. As a result, this project forms a framework for conducting future time-critical removal actions at federal facilities

Nuclear regulatory decision making

International Nuclear Information System (INIS)

2005-01-01

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

77 FR 3828 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of...

Science.gov (United States)

2012-01-25

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66193; File No. SR-ODD-2012-01] Self-Regulatory... to the Options Disclosure Document Reflecting Certain Changes to Disclosure Regarding Relative... disclosure document (``ODD'') to reflect certain changes to disclosure regarding relative performance options...

75 FR 53727 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Approving Proposed Rule Change, as...

Science.gov (United States)

2010-09-01

... underwritings; (ii) supervision of market making commitments; (iii) final approval of advertisements as these... designed to prevent fraudulent and manipulative acts and practices, to promote just and equitable...

77 FR 3531 - Self-Regulatory Organizations; The Depository Trust Company; Order Approving Proposed Rule Change...

Science.gov (United States)

2012-01-24

... Organizations; The Depository Trust Company; Order Approving Proposed Rule Change To Enhance Risk Management.... Description The rule change will enhance the risk management controls associated with DTC's Receiver... Participant's net debit cap is placed on a pending (recycling) queue until another transaction creates...

77 FR 50191 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Instituting Proceedings To...

Science.gov (United States)

2012-08-20

...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Instituting Proceedings To Determine Whether To Approve or Disapprove Proposed Rule Change To Establish ``Benchmark Orders'' Under NASDAQ Rule 4751(f) August 14, 2012. I. Introduction On May 1, 2012, The NASDAQ Stock Market LLC (``NASDAQ'' or ``Exchange...

77 FR 26768 - Determination of Regulatory Review Period for Purposes of Patent Extension; PROLIA

Science.gov (United States)

2012-05-07

... postmenopausal women with osteoporosis at high risk for fracture. Subsequent to this approval, the Patent and..., FDA-2010-E-0660, and FDA-2010-E-0659] Determination of Regulatory Review Period for Purposes of Patent... the Director of Patents and Trademarks, Department of Commerce, for the extension of a patent which...

78 FR 17108 - Approval and Promulgation of Implementation Plans; State of Washington; Revised Format for...

Science.gov (United States)

2013-03-20

...), EPA revised the procedures for IBR'ing Federally-approved SIPs, as a result of consultations between... Violations--Notices 9/8/93 2/22/95, 60 FR 9778 132 Criminal Penalty 11/13/94 10/24/95, 60 FR 54439 133 Civil............ Regulatory Actions & Civil 9/21/95 2/26/97, 62 FR 8624......... Penalties. 400-240......... Criminal...

A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Non-Small Cell Lung Cancer.

Science.gov (United States)

Raju, G K; Gurumurthi, K; Domike, R; Kazandjian, D; Blumenthal, G; Pazdur, R; Woodcock, J

2016-12-01

Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analyses. There is much interest in quantifying regulatory approaches to benefit and risk. In this work the use of a quantitative benefit-risk analysis was applied to regulatory decision-making about new drugs to treat advanced non-small cell lung cancer (NSCLC). Benefits and risks associated with 20 US Food and Drug Administration (FDA) decisions associated with a set of candidate treatments submitted between 2003 and 2015 were analyzed. For benefit analysis, the median overall survival (OS) was used where available. When not available, OS was estimated based on overall response rate (ORR) or progression-free survival (PFS). Risks were analyzed based on magnitude (or severity) of harm and likelihood of occurrence. Additionally, a sensitivity analysis was explored to demonstrate analysis of systematic uncertainty. FDA approval decision outcomes considered were found to be consistent with the benefit-risk logic. © 2016 American Society for Clinical Pharmacology and Therapeutics.

77 FR 74043 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of...

Science.gov (United States)

2012-12-12

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68368; File No. SR-ODD-2012-02] Self-Regulatory... to the Options Disclosure Document Reflecting Certain Changes to Disclosure Regarding Adjustments for... (``November 2012 Supplement'') to amend the options disclosure document (``ODD'') to reflect certain changes...

Directory of certificates of compliance for radioactive materials packages: Report of NRC approved quality assurance programs for radioactive materials packages

International Nuclear Information System (INIS)

1990-10-01

The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of compliance Number is included at the front of Volume 2 of the directory. A listing by packaging types is included in the back of Volume 2. An alphabetical listing by Company name is included in the back of Volume 3 for approved QA programs. The Reports include a listing of all users of each package design and approved QA programs prior to the publication date of the directory

Directory of certificates of compliance for radioactive materials packages: Report of NRC approved quality assurance programs for radioactive materials packages

International Nuclear Information System (INIS)

1989-10-01

The purpose of this directory is to make available a convenient source of information on packaging which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance Number is included at the front of Volume 2 of the directory. A listing by packaging types is included in the back of Volume 2. An alphabetical listing by Company name is included in the back of Volume 3 for approved QA programs. The Reports include a listing of all users of each package design and approved QA programs prior to the publication date of the directory

Bioremediation, regulatory agencies and public acceptance of this technology

International Nuclear Information System (INIS)

Westlake, D. W. S.

1997-01-01

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

76 FR 3684 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of...

Science.gov (United States)

2011-01-20

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63711; File No. SR-ODD-2011-01] Self-Regulatory... to the Options Disclosure Document Reflecting Certain Changes to Disclosure Regarding Credit Default Options in, and Making Certain Technical Amendments to, the June 2007 Supplement to the Options Disclosure...

77 FR 32704 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

Science.gov (United States)

2012-06-01

... securities owned or under management by the institutional customer. The MSRB stated that FINRA Rule 2111....19b-4. \\3\\ The implementation date for Financial Industry Regulatory Authority (``FINRA'') Rule 2111... General Counsel, Securities Industry and Financial Markets Association, dated May 4, 2012 (``SIFMA Letter...

77 FR 40683 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Science.gov (United States)

2012-07-10

.... I. Self-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule Change... senior-level) Floor Official approval, both ``buying and selling members'' must agree to the publication... ``or member organizations'' after ``buying and selling members.'' Rule 2 defines a ``member'' as a...

Transportation of Large Wind Components: A Permitting and Regulatory Review

Energy Technology Data Exchange (ETDEWEB)

Levine, Aaron [National Renewable Energy Lab. (NREL), Golden, CO (United States); Cook, Jeff [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2016-09-01

This report summarizes permitting and regulatory issues associated with transporting wind turbine blades, towers, and nacelles as well as large transformers (wind components). These wind components are commonly categorized as oversized and overweight (OSOW) and require specific permit approvals from state and local jurisdictions. The report was developed based on a Quadrennial Energy Review (QER) recommendation on logistical requirements for the transportation of 'oversized or high-consequence energy materials, equipment, and components.'

Directory of Certificates of Compliance for radioactive materials packages: Report of NRC approved quality assurance programs for radioactive materials packages. Volume 3, Revision 15

International Nuclear Information System (INIS)

1995-10-01

The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance Number is included at the front of Volumes 1 and 2. An alphabetical listing by user name is included in the back of Volume 3 of approved QA programs. The reports include a listing of all users of each package design and approved QA programs prior to the publication date

78 FR 63263 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

Science.gov (United States)

2013-10-23

... internet service providers.\\5\\ \\5\\ Securities Exchange Act Release No. 53980 (June 14, 2006), 71 FR 36155... other things, promote the prompt and accurate clearance and settlement of securities transactions. \\8... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70704; File No. SR-OCC-2013-10] Self-Regulatory...

48 CFR 52.222-16 - Approval of Wage Rates.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Approval of Wage Rates. 52....222-16 Approval of Wage Rates. As prescribed in 22.407(b), insert the following clause: Approval of Wage Rates (FEB 1988) All straight time wage rates, and overtime rates based thereon, for laborers and...

Regulatory agencies and regulatory risk

OpenAIRE

Knieps, Günter; Weiß, Hans-Jörg

2008-01-01

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

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 Program for Medical Devices in Cuba: experiences and current challenges].

Science.gov (United States)

Pereira, Dulce María Martínez; Rodríguez, Yadira Álvarez; Valdés, Yamila Cedeño; Ribas, Silvia Delgado

2016-05-01

Regulatory control of medical devices in Cuba is conducted through a system based on the Regulatory Program for Medical Devices as a way to ensure the safety, efficacy, and effectiveness of these technologies, which are in use by the National Health System. This program was launched in 1992, when the Regulations for State Evaluation and Registration of Medical Devices were approved. Its successive stages and the merging of regulatory activities for drugs and medical equipment have meant progress toward stronger, more transparent strategies and greater control of industry and the National Health System. Throughout its course the Cuban program has met with challenges and difficulties that it has addressed by drawing on its own experiences. During the new period, the greatest challenges revolve around ensuring that regulatory systems incorporate scientific evaluation, risk levels, maximum rigor through the use of technical standards, and the implementation of international recommendations, together with the application of the ISO 13485 certification scheme, enhanced market monitoring, and classification of medical devices in accordance with their relevance to the country's national health policies. From the regional standpoint, the greatest challenge lies in working toward regulatory convergence. The Collaborating Centre for the Regulation of Health Technologies will support the proposed regulatory strategy and established regional priorities, in particular in connection with the implementation of actions involving medical devices.

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.

Assessment of regulatory effectiveness. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1999-09-01

This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

75 FR 22673 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of a...

Science.gov (United States)

2010-04-29

... remove any potential cloud on the jurisdictional status of options or security futures on ETFS Palladium... that are affected by this approval order are essentially the same as the options and security futures... securities transactions and derivative transactions.\\6\\ By amending its By-Laws to help clarify that options...

Timing is everything :

Energy Technology Data Exchange (ETDEWEB)

Kobos, Peter Holmes; Walker, La Tonya Nicole; Malczynski, Leonard A.

2013-10-01

key driver behind each of the TRL, RRL and MRL components individually decreases the time required for the technology to progress through each component by 63, 68 and 64%, respectively. Therefore, under the current working assumptions, to decrease the time it may take for a technology to move from the conceptual stage to full scale market adoption one might consider expending additional effort to secure regulatory approval and reducing the uncertainty of the technologys demand in the marketplace.

Regulatory impacts on the Canadian uranium industry

International Nuclear Information System (INIS)

Frost, S.E.

2001-01-01

The development of environmental and safety regulation in Canada is described and the impacts of these developments on various phases of the uranium industry are examined. In the past 25 years, seven new uranium mining projects, major expansions to four projects, and five uranium refining/conversion projects have undergone environmental assessment in Canada. As regulations and the processes for applying them have developed, the size, complexity and cost of obtaining operating approvals for uranium projects have increased exponentially. Uranium projects are subject to a level of scrutiny that goes far beyond what can be justified by their potential for environmental damage, based primarily on a perceived degree of public concern, rather than any objective measure of environmental risk. The author believes that it is time to re-examine our priorities, to establish some balance between the risks of a project and the assessment effort required. Otherwise, we shall soon find ourselves in the position where smaller projects will never be developed because they cannot cover the regulatory costs. (author)

77 FR 57630 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Approving a Proposed Rule Change Amending...

Science.gov (United States)

2012-09-18

... change was published for comment in the Federal Register on July 30, 2012.\\3\\ The Commission received no comment letters regarding the proposed rule change. This order approves the proposed rule change. \\1\\ 15 U...

Directory of certificates of compliance for radioactive materials packages. Summary report of NRC approved quality assurance programs for radioactive material packages. Volume 3, Revision 4

International Nuclear Information System (INIS)

1984-11-01

This directory contains a Summary Report of NRC Approved Packages (Volume 1), Certificates of Compliance (Volume 2), and a Summary Report of NRC Approved Quality Assurance Programs for Radioactive Material Packages (Volume 3). The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance number is included at the back of each volume of the directory. The Summary Report includes a listing of all users of each package design prior to the publication date of the directory. Shipments of radioactive material utilizing these packagings must be in accordance with the provisions of 49 CFR 173.471 and 10 CFR Part 71, as applicable. In satisfying the requirements of Section 71.12, it is the responsibility of the licensees to insure they have a copy of the current approval and conduct their transportation activities in accordance with an NRC approved quality assurance program. Copies of the current approval may be obtained from the US Nuclear Regulatory Commission Public Document Room files (see Docket No. listed on each certificate) at 1717 H Street, Washington, DC 20555. Note that the general license of 10 CFR 71.12 does not authorize the receipt, possession, use or transfer of byproduct source, or special nuclear material; such authorization must be obtained pursuant to 10 CFR Parts 30 to 36, 40, 50, or 70

76 FR 38231 - Self-Regulatory Organizations; C2 Options Exchange, Incorporated; Order Approving Proposed Rule...

Science.gov (United States)

2011-06-29

... No. 1, To Reduce the Minimum Size of the Nominating and Governance Committee June 22, 2011. I... size of the Nominating and Governance Committee (``NGC'') from seven to five. On May 18, 2011, the..., it had not yet obtained formal approval from its Board of Directors for the specific Bylaw changes...

Slovak Nuclear Regulatory Body Position in the Transport of Radioactive Waste

International Nuclear Information System (INIS)

Homola, J.

2003-01-01

This paper describes safety requirements for transport of radioactive waste in Slovakia and the role of regulatory body in the transport licensing and assessment processes. Importance of radioactive waste shipments have been increased since 1999 by starting of NPP A-1 decommissioning and operation of near surface disposal facility. Also some information from history of shipment as well as future activities are given. Legal basis for radioactive waste transport is resulting from IAEA recommendations in this area. Different types of transport equipment were approved by regulatory body for both liquid and solid waste and transportation permits were issued to their shipment. Regulatory body attention during evaluation of transport safety is focused mainly on ability of individual packages to withstand different transport conditions and on safety analyses performed for transport equipment for liquid waste with high frequency of shipments. During past three years no event was occurred in connection with radioactive waste transport in Slovakia

Recent advances in the management of migraine [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Mark Obermann

2016-11-01

Full Text Available Migraine remains one of the most disabling disorders worldwide. The high prevalence in the general population and the often-delicate treatment of patients account for that. Therapeutic management of migraine relies mainly on non-specific medical treatment and is affected by low patient adherence to the treatment regimens applied. The introduction of specific anti-migraine treatment occurred over 20 years ago when the first triptan was approved by regulatory authorities (sumatriptan, 28 December 1992. Triptan use is limited by side effects, time- and frequency-restricted application, and the risk of developing medication overuse headache. Within the past few years, new and promising drugs such as more specific 5-HT 1F receptor agonists (that is, lasmiditan and monoclonal calcitonin gene-related peptide (CGRP receptor antibodies entered advanced development phases while non-invasive neuromodulatory approaches were suggested to be potentially effective as non-pharmaceutical interventions for migraine.

22 CFR 96.63 - Renewal of accreditation or approval.

Science.gov (United States)

2010-04-01

... for renewal in a timely fashion. Before deciding whether to renew the accreditation or approval of an... accrediting entity or the Secretary during its most current accreditation or approval cycle, the accrediting...

Impact of a Fragmented Regulatory Environment on Sustainable Urban Development Design Management

Directory of Open Access Journals (Sweden)

Kerry Anne London

2009-12-01

Full Text Available The building project development approval process is increasingly complex and fraught with conflict due to the rise of the sustainable urban development movement and inclusive decision making. Coupled with this, government decision-making decentralization has resulted in a fragmented and over-regulated compliance system. Problems arising from the process include wasted resources, excessive time delays, increased holding and litigation costs, inadequate planning coordination, high levels of advocacy costs and a divisive politicized approval process. In Australia, despite attempts by government and industry associations, numerous problems are still unresolved. Design managers increasingly assume a liaison role during the approval phase. There is a long tradition of planning theory literature which provides context for understanding the knowledge-power-participation relationship for this paper. This study investigated the policy, process and practice conflicts during the approval stage in achieving sustainable urban developments. Three regional local government areas within one state jurisdiction and observations from detailed structured focus group interviews involving 23 stakeholders, proposers and assessors were analysed to explore this conflictual environment. As a result of regulatory fragmentation and excessive consultation, various persuasion tactics have been developed by all stakeholders of which `reciprocity' and `authority' were identified as the most common. Two challenges for design managers were thus identified: first, the emergence of the role of a by default central informal arbitrator across conflicting planning instruments; and, second, as a navigator through a set of persuasion tactics. An inclusive knowledge-based design management framework for sustainable urban development is proposed considering Habermas' communicative planning theory, Foucaltian governance and discursive powers thesis and Cialdini's persuasion theory, as

75 FR 63229 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Science.gov (United States)

2010-10-14

...-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate Effectiveness of... hereby given that on October 1, 2010, The NASDAQ Stock Market LLC (``NASDAQ'' or the ``Exchange'') filed... has received approval to launch NASDAQ OMX PSX (``PSX'') \\3\\ as a new platform for trading NMS stocks...

76 FR 2732 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Designation of Longer...

Science.gov (United States)

2011-01-14

...-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Designation of Longer Period for Commission.... Introduction On June 18, 2010, The NASDAQ Stock Market LLC (``Nasdaq'' or the ``Exchange'') filed with the... change. The Commission may extend the period for issuing an order approving or disapproving the proposed...

Regulatory Considerations for the Long Term Cooling Safe Shutdown Requirements of the Passive Residual Heat Removal Systems in Advanced Reactors

International Nuclear Information System (INIS)

Sim, S. K.; Bae, S. H.; Kim, Y. S.; Hwang, Min Jeong; Bang, Young Seok; Hwang, Taesuk

2016-01-01

USNRC approved safe shutdown at 215.6 .deg. C for a safe and long term cooling state for the redundant passive RHRSs by SECY-94-084. USNRC issued COLA(Combined Construction and Operating License) for the Levy County NP Unit-1/2 for the AP1000 passive RHRSs in 2014. Korea Hydro and Nuclear Power(KHNP) is developing APR+ and adopted Passive Auxiliary Feedwater System(PAFS) as a new passive RHRS design. Korea Institute of Nuclear Safety(KINS) has been developing regulatory guides for the advanced safety design features of the advanced ALWRs which has plan to construct in near future in Korea[5]. Safety and regulatory issues as well as the safe shut down requirements of the passive RHRS are discussed and considerations in developing regulatory guides for the passive RHRS are presented herein. Passive RHRSs have been introduced as new safety design features for the advanced reactors under development in Korea. These passive RHRSs have potential advantages over existing active RHRS, however, their functions are limited due to inherent ability of passive heat removal processes. It is high time to evaluate the performance of the passive PRHRs and develop regulatory guides for the safety as well as the performance analyses of the passive RHRS

Case studies on clinical evaluation of biosimilar monoclonal antibody: scientific considerations for regulatory approval.

Science.gov (United States)

Kudrin, Alex; Knezevic, Ivana; Joung, Jeewon; Kang, Hye-Na

2015-01-01

The objective of this paper is to provide considerations based on comprehensive case studies important for regulatory evaluation of monoclonal antibodies as similar biotherapeutic products (SBPs) with a special emphasis on clinical aspects. Scientific principles from WHO Guidelines on SBPs were used as a basis for the exercise. Working groups consisted of regulators, manufacturers and academia. The following topics were discussed by the working groups: clinical criteria for biosimilarity, extrapolation approach and the overall regulatory decision making process. In order to determine typical pitfalls in the design of a SBP clinical programme and evaluate the gap of knowledge, amongst different industry and regulatory stakeholders on the appraisal of the data arising from SBP clinical studies, we have presented two fictional but realistic clinical case studies. The first case consists of the fictional development programme for an infliximab SBP candidate. The second case describes clinical studies proposed for a fictional rituximab SBP candidate. In the first scenario a highly similar quality profile has been taken forward into clinical studies whereas there was an important residual difference in functional attributes for the rituximab SBP candidate. These case studies were presented at the WHO implementation workshop for the WHO guidelines on evaluation of similar biotherapeutic products held in Seoul, Republic of Korea, in May 2014. The goal was to illustrate the interpretation of the clinical data arising from studies with SBP candidates and elicit knowledge gaps in clinical assessment. This paper reflects the outcome of the exercise and discussions held in Seoul and offers an analysis of the case studies as a learning opportunity on clinical development and evaluation of SBPs. Copyright © 2014 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2015-01-01

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

Directory of certificates of compliance for radioactive materials packages. Volume 3, Revision 14: Report of NRC approved quality assurance programs for radioactive materials packages

International Nuclear Information System (INIS)

1994-10-01

This directory contains a Report of NRC Approved Packages (Volume 1), Certificates of Compliance (Volume 2), and a Report of NRC Approved Quality Assurance Programs for Radioactive Materials Packages (Volume 3). The purpose of this directory is to make available a convenient source of information on Quality Assurance Programs and Packagings which have been approved by the US Nuclear Regulatory Commission. Shipments of radioactive material utilizing these packagings must be in accordance with the provisions of 49 CFR section 173.471 and 10 CFR Part 71, as applicable. In satisfying the requirements of Section 71.12, it is the responsibility of the licensees to insure themselves that they have a copy of the current approval and conduct their transportation activities in accordance with an NRC approved quality assurance program

Delay-independent stability of genetic regulatory networks.

Science.gov (United States)

Wu, Fang-Xiang

2011-11-01

Genetic regulatory networks can be described by nonlinear differential equations with time delays. In this paper, we study both locally and globally delay-independent stability of genetic regulatory networks, taking messenger ribonucleic acid alternative splicing into consideration. Based on nonnegative matrix theory, we first develop necessary and sufficient conditions for locally delay-independent stability of genetic regulatory networks with multiple time delays. Compared to the previous results, these conditions are easy to verify. Then we develop sufficient conditions for global delay-independent stability for genetic regulatory networks. Compared to the previous results, this sufficient condition is less conservative. To illustrate theorems developed in this paper, we analyze delay-independent stability of two genetic regulatory networks: a real-life repressilatory network with three genes and three proteins, and a synthetic gene regulatory network with five genes and seven proteins. The simulation results show that the theorems developed in this paper can effectively determine the delay-independent stability of genetic regulatory networks.

Preclinical pharmacokinetics, biodistribution, radiation dosimetry and acute toxicity studies required for regulatory approval of a Clinical Trial Application for a Phase I/II clinical trial of 111In-BzDTPA-pertuzumab

International Nuclear Information System (INIS)

Lam, Karen; Chan, Conrad; Done, Susan J.; Levine, Mark N.; Reilly, Raymond M.

2015-01-01

Introduction: 111 In-BzDTPA-pertuzumab is a novel imaging probe for detecting changes in HER2 expression in breast cancer (BC) caused by treatment with trastuzumab (Herceptin). Our aim was to evaluate the pharmacokinetics, normal tissue biodistribution, radiation dosimetry and acute toxicity of 111 In-BzDTPA-pertuzumab in non-tumor bearing mice in order to obtain regulatory approval to advance this agent to a first-in-humans Phase I/II clinical trial. Methods: Biodistribution and pharmacokinetic studies were performed in non-tumor bearing Balb/c mice injected i.v. with 111 In-BzDTPA-pertuzumab (2.5 MBq; 2 μg). The cumulative number of disintegrations per source organ derived from the biodistribution data was used to predict the radiation absorbed doses in humans using OLINDA/EXM software. Acute toxicity was studied at two weeks post-injection of 111 In-BzDTPA-pertuzumab (1.0 MBq, 20 μg) with comparison to control mice injected with unlabeled BzDTPA-pertuzumab (20 μg) or Sodium Chloride Injection USP. The dose of 111 In-BzDTPA-pertuzumab corresponded to 23-times the human radioactivity dose and 10-times the protein dose on a MBq/kg and mg/kg basis, respectively. Toxicity was assessed by monitoring body mass, complete blood cell count (CBC), hematocrit (Hct), hemoglobin (Hb), serum creatinine (SCr) and alanine aminotransferease (ALT) and by histopathological examination of tissues at necropsy. Results: 111 In-BzDTPA-pertuzumab exhibited a biphasic elimination from the blood with a distribution half-life (t 1/2 α) of 3.8 h and an elimination half-life (t 1/2 β) of 228.2 h. The radiopharmaceutical was distributed mainly in the blood, heart, lungs, liver, kidneys and spleen. The projected whole-body radiation absorbed dose in humans was 0.05 mSv/MBq corresponding to a total of 16.8 mSv for three separate administrations of 111 In-BzDTPA-pertuzumab (111 MBq) planned for the Phase I/II trial. There were slight changes in Hb and SCr levels associated with

75 FR 19436 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving Proposed Rule Change...

Science.gov (United States)

2010-04-14

..., the Commission is not publishing it for comment.\\4\\ This order approves the proposed rule change, as... NASDAQ OMX Corporate Governance Guidelines, however, provide a different standard for uncontested... contained in the Corporate Governance Guidelines; contested elections would remain subject to the plurality...

77 FR 25003 - Self-Regulatory Organizations; NASDAQ OMX Phlx LLC; Order Approving Proposed Rule Change To Amend...

Science.gov (United States)

2012-04-26

...; review and endorsement of customer orders; final approval of advertising or sales literature for use by... and qualified, given the importance and complexity of the rules governing financial responsibility for...

Regulatory requirements for designing PET-CT facility in India

International Nuclear Information System (INIS)

Tandon, Pankaj

2010-01-01

In India, cyclotron-produced radionuclides are gaining importance in molecular imaging in Nuclear Medicine (NM) departments. The importance of this modality among others is due to the fact that it provides valuable clinical information, which was lacking in other available modalities. Presently, every well-established hospital would like to procure Medical Cyclotron or positron emission tomography-computed tomography (PET-CT) facility in their NM department. Because cyclotron-produced radionuclides have higher energy than the other routinely used radionuclides for diagnosis, it becomes essential for the user to know about the regulatory requirement and radiation safety precautions that one has to take for the installation of this new modality in their premises. The various stages of approval of PET-CT facility by the Atomic Energy Regulatory Board (AERB) and important steps that one has to know/follow before planning for this new facility are summarized

Directory of certificates of compliance for radioactive materials packages. Summary report of NRC approved quality assurance programs for radioactive material packages. Volume 3, Revision 6

International Nuclear Information System (INIS)

1986-10-01

This directory contains a Summary Report of NRC Approved Packages (Volumes 1), Certificates of Compliance (Volume 2), and a Summary Report of NRC Approved Quality Assurance Programs for Radioactive Material Packages (Volume 3). The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance number is included at the back of each volume of the directory. The Summary Report includes a listing of all users of each package design prior to the publication date of the directory. Shipments of radioactive material utilizing these packagings must be in accordance with the provisions of 49 CFR 173.471 and 10 CFR Part 71, as applicable. In satisfying the requirements of Section 71.12, it is the responsibility of the licensees to insure them that have a copy of the current approval and conduct their transportation activities in accordance with an NRC approved quality assurance program. Copies of the current approval may be obtained from the US Nuclear Regulatory Commission Public Document Room files (see Docket No. listed on each certificate) at 1717 H Street, Washington, DC 20555. Note that the general license of 10 CFR 71.12 does not authorize the receipt, possession, use of transfer of byproduct source, or special nuclear material; such authorization must be obtained pursuant to 10 CFR Parts 30 to 36, 40, 50, or 70

Virginia Power's regulatory reduction program

International Nuclear Information System (INIS)

Miller, G.D.

1996-01-01

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

Global regulatory developments for clinical stem cell research: diversification and challenges to collaborations.

Science.gov (United States)

Rosemann, Achim; Bortz, Gabriela; Vasen, Federico; Sleeboom-Faulkner, Margaret

2016-10-01

In this article, we explore regulatory developments in stem cell medicine in seven jurisdictions: Japan, China, India, Argentina, Brazil, the USA and the EU. We will show that the research methods, ethical standards and approval procedures for the market use of clinical stem cell interventions are undergoing an important process of global diversification. We will discuss the implications of this process for international harmonization and the conduct of multicountry clinical research collaborations. It will become clear that the increasing heterogeneity of research standards and regulations in the stem cell field presents a significant challenge to international clinical trial partnerships, especially with countries that diverge from the regulatory models that have been developed in the USA and the EU.

The US Food and Drug Administration's tentative approval process and the global fight against HIV.

Science.gov (United States)

Chahal, Harinder Singh; Murray, Jeffrey S; Shimer, Martin; Capella, Peter; Presto, Ryan; Valdez, Mary Lou; Lurie, Peter G

2017-12-01

In 2004, the US government began to utilize the Food and Drug Administration's (USFDA) tentative approval process (tFDA) as a basis to determine which HIV drugs are appropriate to be purchased and used in resource-constrained settings. This process permits products that are not approved for marketing in the US, including medicines with active patents or marketing restrictions in the US, to be purchased and distributed in resource-constrained settings. Although the tFDA was originally intended to support the United States' President's Emergency Plan for AIDS Relief (PEPFAR), the USFDA list has become a cornerstone of international HIV programmes that support procurement of ARVs, such as the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Our objective in this article is to help the global HIV policy makers and implementers of HIV programmes better understand the benefits and limitations of the tFDA by providing an in-depth review of the relevant legal and regulatory processes. USFDA's dedicated tFDA process for ARVs used by the PEPFAR programme has a wide impact globally; however, the implementation and the regulatory processes governing the programme have not been thoroughly described in the medical literature. This paper seeks to help stakeholders better understand the legal and regulatory aspects associated with review of ARVs under the tFDA by describing the following: (1) the tFDA and its importance to global ARV procurement; (2) the regulatory pathways for applications under tFDA for the PEPFAR programme, including modifications to applications, review timelines and costs; (3) the role of US patents, US marketing exclusivity rights, and the Medicines Patents Pool in tFDA; and (4) an overview of how applications for PEPFAR programme are processed through the USFDA. We also provide a case study of a new ARV, tenofovir alafenamide fumarate (TAF), not yet reviewed by USFDA for PEPFAR use. In this paper, we describe the

Directory of certificates of compliance for radioactive materials packages: summary report of NRC approved quality-assurance programs for radioactive-material packages. Volume 3, Revision 3

International Nuclear Information System (INIS)

1983-09-01

This directory contains a Summary Report of NRC Approved Packages (Volume 1), Certificates of Compliance (Volume 2), and a Summary Report of NRC Approved Quality Assurance Programs for Radioactive Material Packages (Volume 3). The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the US Nuclear Regulatory Commission. To assist in identifying packaging, an index by Model Number and corresponding Certificate of Compliance number is included at the back of each volume of the directory. The Summary Report includes a listing of all users of each package design prior to the publication date of the directory. Shipments of radioactive material utilizing these packagings must be in accordance with the provisions of 49 CFR 173.471 and 10 CFR Part 71, as applicable. In satisfying the requirements of Section 71.12, it is the responsibility of the licensees to insure them in accordance with an NRC approved quality assurance program. Copies of the current approval may be obtained from the US Nuclear Regulatory Commission Public Document Room files (see Docket No. listed on each certificate) at 1717 H Street, Washington, DC 20555. Note that the general license of 10 CFR 71.12 does not authorize the receipt, possession, use or transfer of byproduct source, or special nuclear material; such authorization must be obtained pursuant to 10 CFR Parts 30 to 36, 40, 50, or 70

78 FR 41852 - Hours of Service for Commercial Motor Vehicle Drivers; Regulatory Guidance Concerning Off-Duty Time

Science.gov (United States)

2013-07-12

... provided: 1. The driver is relieved of all duty and responsibility for the care and custody of the vehicle... Service for Commercial Motor Vehicle Drivers; Regulatory Guidance Concerning Off-Duty Time AGENCY: Federal... motor vehicle (CMV) driver to record meal and other routine stops made during a work shift as off-duty...

APPROVAL OF WASTE TREATMENT AND IMMOBILIZATION PLANT CONTRACTOR-INITIATED AUTHORIZATION BASIS AMENDMENT REQUESTS (ABAR)

International Nuclear Information System (INIS)

JONES GL

2008-01-01

The objective is to describe the process used by the Office of River Protection (ORP) for evaluating and implementing Contractor-initiated changes to the Waste Treatment and Immobilization Plant (WTP) Authorization Basis (AB). The WTP Project's history has provided a unique challenge for establishing and maintaining an ORP-approved AB during design and construction. Until operations begin, the project cannot implement the classic Unreviewed Safety Question (USQ) process to determine when ORP approval of Contractor-initiated changes is required. A 'quasiUSQ' process has been implemented that defines when AB changes could occur. The three types of AB changes are (1) Limited Scope Changes, (2) Authorization Basis Deviations, and (3) Authorization Basis Amendment Request (ABAR). DOE RL/REG 97-13, 'Office of River Protection Position on Contractor-Initiated Changes to the Authorization Basis', describes the process the WTP Contractor must follow to make changes to the AB, with and without ORP approval. The process uses a 'safety evaluation' process that is similar to the USQ process but at a more qualitative level. The maturation of the WTP Contractor's facility design and activities, and other changing conditions, resulted in a process that allows the Contractor to make changes to the AB without ORP approval; however, those changes that may significantly affect nuclear safety do require ORP approval. This process balances the WTP regulatory principle of efficiency with assurance that adequate safety will not be compromised. The process has reduced the number of ABARs requiring ORP approval and reduced the potential for delays in design and procurement activities

77 FR 27255 - Self-Regulatory Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To...

Science.gov (United States)

2012-05-09

... Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To Reduce the Current Level of Risk Mutualization Among Clearing Participants and To Modify the Initial Margin Risk Model So That It Is Easier for... modifications to its risk model for clearing credit default swaps (``CDS'') contracts. For the first...

Irradiation: Technology whose time has come?

International Nuclear Information System (INIS)

Schechter, M.

1985-01-01

The characteristics and application of food irradiation are briefly discussed, noting FDA's recent approval of the use of this technology to kill trichnella spirals in pork. Despite public concerns, food irradiation sources (gamma rays from Co-60 and Cs-137) are reported to leave no radioactivity in irradiated foods when used under FDA-approved guidelines. Food irradiation was legally ruled to be a 'food additive' by Congress in 1958 with FDA having regulatory authority; however, while low-level dosing has received FDA approval for sprout inhibition in root crops and as an insect control, concerns about cost-effectiveness, safety, and consumer acceptability have continued to limit high dose food irradiation (i.e., exposure to over 1000krad). The future acceptance of food irradiation still, primarily rests in the hands of food service professionals and their consumers

78 FR 46665 - Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Notice of Filing...

Science.gov (United States)

2013-08-01

... directors, governors, officers, employees or representatives. No warranties, express or implied, are made by... participant.\\12\\ On October 9, 2008, the Commission approved an amendment to the Plan to clarify that the term... relieved of regulatory responsibility for that common member, pursuant to the terms of the Plan, with...

75 FR 500 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving a Proposed Rule...

Science.gov (United States)

2010-01-05

.... 61043 (November 20, 2009), 74 FR 62612. On January 22, 2009, the Commission approved the formation of... wholly-owned subsidiary, NYSE Market, Inc., owns less than 9% of the aggregate limited partnership... proposed rule's impact on efficiency, competition, and capital formation. See 15 U.S.C. 78c(f). \\12\\ 15 U.S...

Dynamic RSA: Examining parasympathetic regulatory dynamics via vector-autoregressive modeling of time-varying RSA and heart period.

Science.gov (United States)

Fisher, Aaron J; Reeves, Jonathan W; Chi, Cyrus

2016-07-01

Expanding on recently published methods, the current study presents an approach to estimating the dynamic, regulatory effect of the parasympathetic nervous system on heart period on a moment-to-moment basis. We estimated second-to-second variation in respiratory sinus arrhythmia (RSA) in order to estimate the contemporaneous and time-lagged relationships among RSA, interbeat interval (IBI), and respiration rate via vector autoregression. Moreover, we modeled these relationships at lags of 1 s to 10 s, in order to evaluate the optimal latency for estimating dynamic RSA effects. The IBI (t) on RSA (t-n) regression parameter was extracted from individual models as an operationalization of the regulatory effect of RSA on IBI-referred to as dynamic RSA (dRSA). Dynamic RSA positively correlated with standard averages of heart rate and negatively correlated with standard averages of RSA. We propose that dRSA reflects the active downregulation of heart period by the parasympathetic nervous system and thus represents a novel metric that provides incremental validity in the measurement of autonomic cardiac control-specifically, a method by which parasympathetic regulatory effects can be measured in process. © 2016 Society for Psychophysiological Research.

Recent Advances in Drug Development and Regulatory Science in China.

Science.gov (United States)

Chen, Jie; Zhao, Naiqing

2018-01-01

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

The PREEV project of the Latin American Forum.Regulatory practices on aging and life extension; El proyecto {sup P}reev del Foro Iberoamericano. Practicas reguladoras en envejecimiento y extension de vida.

Energy Technology Data Exchange (ETDEWEB)

Figueras, J. M.

2011-07-01

The American Forum Plenary approved in 2008 the PREEV project, Regulatory Practices in Aging and Life Extension, whose main objective is to improve the regulatory action with regard to the management programs of life and long-term operation of nuclear power plants in the countries of the region Latin American.

Directory of certificates of compliance for radioactive materials packages. Volume 3, revision 1. Summary report of NRC approved quality assurance programs for radioactive material packages

International Nuclear Information System (INIS)

1981-12-01

The directory contains a Summary Report of NRC approved Packages (Volume 1), Certificates of Compliance (Volume 2), and a Summary Report of NRC Approved Quality Assurance Programs for Radioactive Material Packages (Volume 3). The purpose of this directory is to make available a convenient source of information on packagings which have been approved by the U.S. Nuclear Regulatory Commission. To assist in identifying packaging, and index by Model Number and corresponding Certificate of Compliance number is included at the back of each volume of the directory. The Summary Report includes a listing of all users of each package design prior to the publication date of the directory

Proposed Changes to EPA's Transuranic Waste Characterization Approval Process

International Nuclear Information System (INIS)

Joglekar, R.D.; Feltcorn, E.M.; Ortiz, A.M.

2003-01-01

This paper describes the changes to the waste characterization (WC) approval process proposed in August 2002 by the U.S. Environmental Protection Agency (EPA or the Agency or we). EPA regulates the disposal of transuranic (TRU) waste at the Waste Isolation Pilot Plant (WIPP) repository in Carlsbad, New Mexico. EPA regulations require that waste generator/storage sites seek EPA approval of WC processes used to characterize TRU waste destined for disposal at WIPP. The regulations also require that EPA verify, through site inspections, characterization of each waste stream or group of waste streams proposed for disposal at the WIPP. As part of verification, the Agency inspects equipment, procedures, and interviews personnel to determine if the processes used by a site can adequately characterize the waste in order to meet the waste acceptance criteria for WIPP. The paper discusses EPA's mandate, current regulations, inspection experience, and proposed changes. We expect that th e proposed changes will provide equivalent or improved oversight. Also, they would give EPA greater flexibility in scheduling and conducting inspections, and should clarify the regulatory process of inspections for both Department of Energy (DOE) and the public

75 FR 36136 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Approving Proposed Rule Change To Amend...

Science.gov (United States)

2010-06-24

... is the practice of NYSE Euronext's Global Risk and Audit Services Department (``RAS''), which...) and Section 401(a) of the Exchange's Bylaws To Eliminate the Exchange's Audit Committee, Compensation... eliminate the Exchange's Audit Committee, Compensation Committee, and Regulatory Oversight Committee. The...

Regulatory requirements and quality assurance of radiation monitoring instruments

International Nuclear Information System (INIS)

Narasimharao, K.L.; Sharma, Ranjit

2005-01-01

The successful utilisation of radiation sources in the fields of medicine and industry requires the accurate measurement of activity, exposure rate and dose. Many varieties of instruments are in use for measurement of these parameters and new ones are being developed. The criteria for the design of the radiation monitoring instrument include the type and intensity of the radiation, purpose of measurement and ruggedness of the instrument. Quality and reliability of radiation monitoring instruments ensure that individuals are adequately protected. Accuracy, response time and ruggedness are required to be as per the approved/ prescribed guidelines. Regulatory authorities outline the design and performance criteria for radiation monitoring instruments and prescribe the recommendations of international agencies such as IAEA, ICRU and ISO for radiological measurement assurance programme. National Standards Laboratories all over the world prescribe procedures for calibration of various radiation monitoring instruments. The instruments should be calibrated as per these guidelines and should be traceable to national standards. The calibration traceable to national/ international standards and documentation as well as limits stipulated by the competent authority ensures the expected performance of the instrument. (author)

The revised version of the German Radiation Protection Regulatory Guide for Medical Applications (Richtlinie Strahlenschutz in der Medizin)

International Nuclear Information System (INIS)

Kemmer, W.

1995-01-01

The revised version of the regulatory guide, effective since 1 June 1993, is intended to enhance and effect in practice a harmonisation of approval and acceptance procedures and standardized testing processes for acceptance and approval, as well as to facilitate governmental supervisory functions relating to the application of radioactive substances and ionizing radiation in the medical field. The guide can furthermore serve as a useful source of reference and information for doctors or medical personnel being trained in applying the Radiation Protection Ordinance, or for acquisition of the required expert knowledge in medical radiological protection. (orig./HP) [de

76 FR 79729 - Self-Regulatory Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To...

Science.gov (United States)

2011-12-22

... plc as signatories. II. Self-Regulatory Organization's Statement of the Terms of Substance of the... is the recognition that CDS contracts cleared by ICC referencing broad-based securities indices are... would, among other things, decompose CDS contracts referencing broad-based [[Page 79730

Non-fragile observer design for discrete-time genetic regulatory networks with randomly occurring uncertainties

International Nuclear Information System (INIS)

Banu, L Jarina; Balasubramaniam, P

2015-01-01

This paper investigates the problem of non-fragile observer design for a class of discrete-time genetic regulatory networks (DGRNs) with time-varying delays and randomly occurring uncertainties. A non-fragile observer is designed, for estimating the true concentration of mRNAs and proteins from available measurement outputs. One important feature of the results obtained that are reported here is that the parameter uncertainties are assumed to be random and their probabilities of occurrence are known a priori. On the basis of the Lyapunov–Krasovskii functional approach and using a convex combination technique, a delay-dependent estimation criterion is established for DGRNs in terms of linear matrix inequalities (LMIs) that can be efficiently solved using any available LMI solver. Finally numerical examples are provided to substantiate the theoretical results. (paper)

Assessment of Quality Assurance Measures for Radioactive Material Transport Packages not Requiring Competent Authority Design Approval - 13282

International Nuclear Information System (INIS)

Komann, Steffen; Groeke, Carsten; Droste, Bernhard

2013-01-01

The majority of transports of radioactive materials are carried out in packages which don't need a package design approval by a competent authority. Low-active radioactive materials are transported in such packages e.g. in the medical and pharmaceutical industry and in the nuclear industry as well. Decommissioning of NPP's leads to a strong demand for packages to transport low and middle active radioactive waste. According to IAEA regulations the 'non-competent authority approved package types' are the Excepted Packages and the Industrial Packages of Type IP-1, IP-2 and IP-3 and packages of Type A. For these types of packages an assessment by the competent authority is required for the quality assurance measures for the design, manufacture, testing, documentation, use, maintenance and inspection (IAEA SSR 6, Chap. 306). In general a compliance audit of the manufacturer of the packaging is required during this assessment procedure. Their regulatory level in the IAEA regulations is not comparable with the 'regulatory density' for packages requiring competent authority package design approval. Practices in different countries lead to different approaches within the assessment of the quality assurance measures in the management system as well as in the quality assurance program of a special package design. To use the package or packaging in a safe manner and in compliance with the regulations a management system for each phase of the life of the package or packaging is necessary. The relevant IAEA-SSR6 chap. 801 requires documentary verification by the consignor concerning package compliance with the requirements. (authors)

Assessment of Quality Assurance Measures for Radioactive Material Transport Packages not Requiring Competent Authority Design Approval - 13282

Energy Technology Data Exchange (ETDEWEB)

Komann, Steffen; Groeke, Carsten; Droste, Bernhard [BAM Federal Institute for Materials Research and Testing, Unter den Eichen 44-46, 12203 Berlin (Germany)

2013-07-01

The majority of transports of radioactive materials are carried out in packages which don't need a package design approval by a competent authority. Low-active radioactive materials are transported in such packages e.g. in the medical and pharmaceutical industry and in the nuclear industry as well. Decommissioning of NPP's leads to a strong demand for packages to transport low and middle active radioactive waste. According to IAEA regulations the 'non-competent authority approved package types' are the Excepted Packages and the Industrial Packages of Type IP-1, IP-2 and IP-3 and packages of Type A. For these types of packages an assessment by the competent authority is required for the quality assurance measures for the design, manufacture, testing, documentation, use, maintenance and inspection (IAEA SSR 6, Chap. 306). In general a compliance audit of the manufacturer of the packaging is required during this assessment procedure. Their regulatory level in the IAEA regulations is not comparable with the 'regulatory density' for packages requiring competent authority package design approval. Practices in different countries lead to different approaches within the assessment of the quality assurance measures in the management system as well as in the quality assurance program of a special package design. To use the package or packaging in a safe manner and in compliance with the regulations a management system for each phase of the life of the package or packaging is necessary. The relevant IAEA-SSR6 chap. 801 requires documentary verification by the consignor concerning package compliance with the requirements. (authors)

38 CFR 17.65 - Approvals and provisional approvals of community residential care facilities.

Science.gov (United States)

2010-07-01

... approvals of community residential care facilities. 17.65 Section 17.65 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Community Residential Care § 17.65 Approvals and provisional approvals of community residential care facilities. (a) An approval of a facility meeting all of...

Risk literacy for scientists. Invitation to regulatory science

International Nuclear Information System (INIS)

Ono, Kyoko

2012-01-01

This paper discusses a regulatory science, which fills a gap between scientific knowledge and regulatory actions. The author provides examples of the regulatory science employed in chemical risk assessment, such as the linear non-threshold theory. In the regulatory science, scientific data as well as scientific reasoning based on scientific knowledge - or regulatory rules - should play an important role. It is important to recognize that the rules facilitate transparent decision making under conditions of uncertainty and time constraints. Furthermore, the development of traditional or pure science results in the validation of regulatory rules, and subsequently, the regulatory science procedure develops more systematically. The concept of this science should be understood by those engaged in governmental decision making. (author)

77 FR 42349 - Self-Regulatory Organizations; NYSE Amex LLC; Order Approving a Proposed Rule Change Defining a...

Science.gov (United States)

2012-07-18

... ATP Holders via Regulatory Bulletin regarding the rule change. The Exchange plans to issue notice....\\7\\ \\7\\ See Notice, supra note 3, at 32158. III. Discussion The Commission finds that the proposed...

A guide to approaching regulatory considerations for lentiviral-mediated gene therapies.

Science.gov (United States)

White, Michael; Whittaker, Roger; Stoll, Elizabeth Ann

2017-06-12

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well-characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is non-pathogenic and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations, and how they are administered in the United Kingdom, although many of the principles will be similar for other regions including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarises the extant regulatory guidance for gene therapies, categorised as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy.

Biosimilars approval process.

Science.gov (United States)

Zuñiga, Leyre; Calvo, Begoña

2010-04-01

For similar biological medicinal products, the so-called biosimilars, clinical trials are required rather than just the bioequivalence studies required to support the registration of a generic small molecule drug product. The EU Directive 2001/83/EC, as amended, stated that where a biological medicinal product which is similar to a reference biological product, does not meet the conditions in the definition of generic medicinal products the results of appropriate pre-clinical tests or clinical trials relating to these conditions must be provided. The challenge is to determine the exact nature of the non-clinical and clinical programme required to gain regulatory approval. The applicant is encouraged to provide a detailed description of the strategy used to demonstrate the biosimilar and the reference product have similar profiles in terms of quality, safety and efficacy. The extent to which comparability can be proven will have quite an impact on how many non-clinical and clinical studies the biosimilar applicant will be required to conduct. The dossier submitted by the applicant to the EMEA should cover all aspects of the comparability assessment and must include data on possible unwanted immune reactions to the therapeutic protein. Post-marketing pharmacovigilance plans are also expected to be included in the biosimilar dossier. Copyright 2009 Elsevier Inc. All rights reserved.

As to achieve regulatory action, regulatory approaches

International Nuclear Information System (INIS)

Cid, R.; Encinas, D.

2014-01-01

The achievement of the effectiveness in the performance of a nuclear regulatory body has been a permanent challenge in the recent history of nuclear regulation. In the post-Fukushima era this challenge is even more important. This article addresses the subject from two complementary points of view: the characteristics of an effective regulatory body and the regulatory approaches. This work is based on the most recent studies carried out by the Committee on Nuclear Regulatory Activities, CNRA (OECD/NEA), as well as on the experience of the Consejo de Seguridad Nuclear, CSN, the Spanish regulatory body. Rafael Cid is the representative of CSN in these project: Diego Encinas has participated in the study on regulatory approaches. (Author)

Safety system upgrades to a research reactor: A regulatory perspective

International Nuclear Information System (INIS)

Lamarre, G.B.; Martin, W.G.

2003-01-01

The NRU (National Research Universal) reactor, located at the Chalk River Laboratories of Atomic Energy of Canada Limited (AECL), first achieved criticality November 3, 1957. AECL continues to operate NRU for research to support safety and reliability studies for CANDU reactors and as a major supplier of medical radioisotopes. Following a detailed systematic review and assessment of NRU's design and the condition of its primary systems, AECL formally notified the Canadian Nuclear Safety Commission's (CNSC) predecessor - the Atomic Energy Control Board - in 1992 of its intention to upgrade NRU's safety systems. AECL proposed seven major upgrades to provide improvements in shutdown capability, heat removal, confinement, and reactor monitoring, particularly during and after a seismic event. From a CNSC perspective, these upgrades were necessary to meet modern safety standards. From the start of the upgrades project, the CNSC provided regulatory oversight aimed at ensuring that AECL maintained a structured approach to the upgrades. The elements of the approach include, but are not limited to, the determination of project milestones and target dates; the formalization of the design process and project quality assurance requirements; the requirements for updated documentation, including safety reports, safety notes and commissioning reports; and the approval and authorization process. This paper details, from a regulatory perspective, the structured approach used in approving the design, construction, commissioning and subsequent operation of safety system upgrades for an existing and operating research reactor, including the many challenges faced when attempting to balance the requirements of the upgrades project with AECL's need to keep NRU operating to meet its important research and production objectives. (author)

French regulatory approach to establishing the safety case for ageing NPP's

International Nuclear Information System (INIS)

Delage, M.

1994-06-01

The French regulatory procedures make provision for three main stages in the safety assessment of nuclear power plants. The first stage ends up with the construction licence and focuses on the assessment of the preliminary safety report. The second stage makes it possible to issue the fuel loading approval following evaluation of the provisional safety report. The third stage permits to declare the start of normal operation of the installation. The procedure, the tests and the assessment forming the overall strategy for safety regulations are described in detail. (R.P.)

Regulatory difficulties in a developing country

International Nuclear Information System (INIS)

Jacobs, W.R. Jr.

1978-01-01

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

Regulatory challenges in the review of data from global clinical trials: the PMDA perspective.

Science.gov (United States)

Asano, K; Tanaka, A; Sato, T; Uyama, Y

2013-08-01

Regulatory agencies face challenges in reviewing data from global clinical trials (GCTs) in the era of globalization of drug development. One major challenge is consideration of ethnic factors in evaluating GCT data so as to extrapolate foreign population data to one's own national population. Here, we present the Pharmaceuticals and Medical Devices Agency (PMDA) perspective in reviewing GCT data in new drug applications (NDAs) and discuss future challenges for new drug approval.

The theory of the regulatory bodies and the CSN; La teoria de las entidades reguladoras y el CSN

Energy Technology Data Exchange (ETDEWEB)

Gamir Casares, L.

2011-07-01

In this article the vice president of the Nuclear Safety Council and professor of Economics and Politics, Luis Gamir, analyses the theoretical nature of the role played by regulatory organisations in democratic societies and the keys of their credibility, with special reference to the Council and the Strategic Plan recently approved for the period 2011-2016. (Author)

An extended Kalman filtering approach to modeling nonlinear dynamic gene regulatory networks via short gene expression time series.

Science.gov (United States)

Wang, Zidong; Liu, Xiaohui; Liu, Yurong; Liang, Jinling; Vinciotti, Veronica

2009-01-01

In this paper, the extended Kalman filter (EKF) algorithm is applied to model the gene regulatory network from gene time series data. The gene regulatory network is considered as a nonlinear dynamic stochastic model that consists of the gene measurement equation and the gene regulation equation. After specifying the model structure, we apply the EKF algorithm for identifying both the model parameters and the actual value of gene expression levels. It is shown that the EKF algorithm is an online estimation algorithm that can identify a large number of parameters (including parameters of nonlinear functions) through iterative procedure by using a small number of observations. Four real-world gene expression data sets are employed to demonstrate the effectiveness of the EKF algorithm, and the obtained models are evaluated from the viewpoint of bioinformatics.

Right to experimental treatment: FDA new drug approval, constitutional rights, and the public's health.

Science.gov (United States)

Leonard, Elizabeth Weeks

2009-01-01

On May 2, 2006, a divided panel of the U.S. Court of Appeals for the District of Columbia, in a startling opinion, Abigail Alliance for Better Access to Developmental Drugs v. Eschenbach, held that terminally ill patients who have exhausted all other available options have a constitutional right to experimental treatment that FDA has not yet approved. Although ultimately overturned by the full court, Abigail Alliance generated considerable interest from various constituencies. Meanwhile, FDA proposed similar regulatory amendments, as have lawmakers on both sides of the aisle in Congress. But proponents of expanded access fail to consider public health and consumer safety concerns. In particular, allowing patients to try unproven treatments, outside of controlled clinical trials risks both the study's outcome and the health of patients who might benefit from the deliberate, careful process of new drug approval as it currently operates under FDA's auspices.

Regulatory authority infrastructure for Namibia

International Nuclear Information System (INIS)

Shangula, K.

2001-01-01

The Republic of Namibia is participating in the International Atomic Energy Agency's Model Project for the Improvement of National Regulatory Authority Infrastructures in Member States. The paper illustrates our experience in solving problems and difficulties confronted in establishing an effective regulatory authority operating within the existing national infrastructure that should be supported by the Government. An effective regulatory authority is seen as part of the wider administrative scope of our Government through ministerial mandates given by the State from time to time, guaranteeing its independence when implementing legal provisions under statutes. Sections of the report illustrate our experience in the following areas: 1. National radiation protection policy 2. Structure of our national regulatory authority 3. Laws and regulations 4. Provisions for notification, authorization and registration 5. In-depth security measures for radiation sources and radioactive material 6. Systems for the inspection of radiation sources, radioactive materials, enforcement of legal provisions 7. Extent of the applications of radiation sources and radioactive materials in the country. The paper provides information regarding existing Government policy on radiation protection; structure and legal aspects of the national regulatory, including statutes and regulations; the extent of application and uses of radiation sources and security of radioactive materials; human resources: strengths and constraints; management practices and financing of regulatory authority; and plans for emergency recovery of orphan sources. National plans for management of disused sources, recovery of orphan sources, abnormal emergencies, communication of information to affected persons on exposure effects, and the safety training of persons using these applications are discussed. the paper provides a summary and some suggestions of the way forward for Namibia. (author)

The current status of the debate on socio-economic regulatory assessments: positions and policies in Canada, the USA, the EU and developing countries

NARCIS (Netherlands)

Falck-Zepeda, J.; Wesseler, J.H.H.; Smyth, S.

2013-01-01

Article 26.1 of the Cartagena Protocol on Biosafety has the option of considering socio-economic issues in biosafety regulatory approval processes related to genetically engineered organisms. National laws and regulations in some countries have already defined positions and may have enacted policies

Specific problems and practical experience of regulatory inspection during commissioning in the United Kingdom

International Nuclear Information System (INIS)

Lewis, G.

1977-01-01

The commissioning of nine Magnox and two Advanced Gas-cooled Reactor Nuclear Power Plants in the United Kingdom during the last sixteen years under the regulatory control of the Nuclear Installations Inspectorate of the Health and Safety Executive has been based on a Stage Approval Philosophy starting with proof-testing of the primary gas circuit and concluding with tests on the reactor at full power. The practical experience gained during this period has enabled the Nuclear Installations Inspectorate to rationalise the procedures and test requirements without comporomising safety standards. The Operating Rules and Maintenance Schedules are approved for commissioning and during this period are reviewed for their adequacy for future power operation of the plant. The organisation, documentation, test procedures and the commissioning programme used for the Advanced Gas-cooled Reactors are briefly explained. (author)

Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - Slovenia

International Nuclear Information System (INIS)

2013-01-01

This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment; 4. Nuclear installations (Licensing and inspection, including nuclear safety; Emergency response); 5. Trade in nuclear materials and equipment; 6. Safeguards for nuclear material; 7. Radiation protection; 8. Radioactive waste management; 9. Nuclear security; 10. Transport; 11. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Slovenian Nuclear Safety Administration - SNSA; Slovenian Radiation Protection Administration - SRPA); 2. Advisory bodies; 3. Public and semi-public agencies; 4. Technical support organisations - approved experts

19 CFR 115.41 - Certificate of approval for containers approved after manufacture.

Science.gov (United States)

2010-04-01

... after manufacture. 115.41 Section 115.41 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT... PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS Procedures for Approval of Containers After Manufacture § 115.41 Certificate of approval for containers approved after manufacture. The Certifying Authority shall...

The expanding regulatory universe of p53 in gastrointestinal cancer [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Andrew Fesler

2016-04-01

Full Text Available Tumor suppresser gene TP53 is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs through direct binding to the promoter region of these miRNAs.  Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs. Like miRNA, lncRNAs have been found to play important roles in cancer biology.  With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

Prediction of regulatory elements

DEFF Research Database (Denmark)

Sandelin, Albin

2008-01-01

Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet......-lab methods are time consuming and expensive, it is not realistic to identify TFBS for all uncharacterized genes in the genome by purely experimental means. Computational methods aimed at predicting potential regulatory regions can increase the efficiency of wet-lab experiments significantly. Here, methods...

Canadian and international approaches to regulatory effectiveness

International Nuclear Information System (INIS)

Lojk, R.

2014-01-01

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

Basic regulatory requirements for carrying out investigations, reasoning and the approving of the disposal of radioactive and other industrial waste in geological formations in the U.S.S.R

International Nuclear Information System (INIS)

Pimenov, M.K.

1980-01-01

Legislation and other regulatory standards in force or in preparation in the USSR relating to the disposal and storage of radioactive and other industrial wastes in underground formations are discussed in the report. A tentative outline of the basic operations involved in the disposal of radioactive and other industrial wastes into geological formations is given. Supervision, control and penalties provided by law are also discussed. Conclusions are made that the comparison of national legislative instruments and regulatory documents and procedures relating to underground disposal of radioactive and industrial wastes into geological formations is timely and urgent. (author)

Biosimilars for psoriasis: worldwide overview of regulatory guidelines, uptake and implications for dermatology clinical practice.

Science.gov (United States)

Cohen, A D; Wu, J J; Puig, L; Chimenti, S; Vender, R; Rajagopalan, M; Romiti, R; de la Cruz, C; Skov, L; Zachariae, C; Young, H S; Foley, P; van der Walt, J M; Naldi, L; Prens, E P; Blauvelt, A

2017-12-01

The introduction of biological drugs for the treatment of patients with psoriasis has revolutionized treatment paradigms and enabled numerous patients to achieve disease control with an acceptable safety profile. However, the high cost of biologics limits access to these medications for the majority of patients worldwide. In recent years, the introduction of biosimilars for inflammatory diseases has become a fast evolving field. The future use of biosimilars offers the potential for decreased cost and increased access to biologics for patients with psoriasis. For approval of biosimilars, different regulatory agencies use highly variable methods for definition, production, approval, marketing and postmarketing surveillance. Due to potential interchangeability between biologics and biosimilars, traceability and pharmacovigilance are required to collect accurate data about adverse events in patients with psoriasis; spontaneous reporting, registries and use of 'big data' should facilitate this process on a global basis. The current article describes biosimilar regulatory guidelines and examples of biosimilar uptake in clinical practice in several countries around the world. As it is apparent that biological therapy treatment decisions may become more physician independent, the International Psoriasis Council recommends that dermatologists should take an active role in the development of biosimilar prescribing policies with their respective healthcare settings and government agencies. © 2017 British Association of Dermatologists.

Setting up a randomized clinical trial in the UK: approvals and process.

Science.gov (United States)

Greene, Louise Eleanor; Bearn, David R

2013-06-01

Randomized clinical trials are considered the 'gold standard' in primary research for healthcare interventions. However, they can be expensive and time-consuming to set up and require many approvals to be in place before they can begin. This paper outlines how to determine what approvals are required for a trial, the background of each approval and the process for obtaining them.

Regulatory control and challenges in Medical facilities using ionising radiation sources

International Nuclear Information System (INIS)

Agarwal, S.P.

2008-01-01

Medical facilities utilising ionising radiation sources for diagnostic and treatment of cancer are regulated under the provisions of Atomic Energy (Radiation Protection) Rules, 2004 promulgated under the Atomic Energy Act 1962. The Competent Authority for the enforcement of the rules is Chairman, Atomic Energy Regulatory Board (AERB). Practice specific codes are issued by AERB for medical facilities such as Radiotherapy, Nuclear Medicine and Radiology. Regulatory process for control of medical facilities covers the entire life cycle of the radiation sources in three stages viz pre-Iicensing, during useful life and decommissioning and disposal. Pre-Iicensing requirements include use of type approved sources and equipment, approval of design layout of the facility and installation, exclusive (safe and secure) source storage facility when the equipment is not in use, radiation (area/individual) monitoring devices, qualified, trained and certified manpower, emergency response plans and commitment from the licensee for the safe disposal of disused/decayed sources. Compliance to these requirements makes the applicant eligible to obtain license from AERB for the operation of the medical facility. During the use of radiation sources, specific prior approval of the Competent Authority is required in respect of every source replacement, sale, transfer, transport, import and export. Further, all licensees are required to send the periodic safety Status reports to AERB as well as reporting of any off normal events. AERB conducts inspection of the facilities to ensure compliance with the safety requirements during operation of the facility. Violation of safety norms by licensee attracts enforcement action which includes suspension, modification or withdrawal of licensee for operation of the facility. Upon completion of the useful life of the source, the licensee decommissions the facility and returns the source to the original supplier. For returning the source, prior

Grandfathering of competent authority approved packages

International Nuclear Information System (INIS)

Osgood, N.L.

2004-01-01

International Atomic Energy Agency transportation regulations are reviewed and revised on a periodic basis as new technical and scientific information becomes available. The 1996 Edition of the Regulations for the Safe Transport of Radioactive Materials in TS-R-1 includes provisions for the use of package designs approved to previous editions of the regulations. This assures that there is no disruption of transport when the regulations are updated and revised. The revision of package design standards may make certain designs obsolete, though not necessarily unsafe. The U.S. Nuclear Regulatory Commission is the agency in the United States that certifies transportation packages for Type B and fissile materials. NRC regulations include grandfathering provisions that are comparable to and compatible with the IAEA standards. NRC staff is promoting a new system that would eliminate the need to grandfather package designs. Under the new method, any new or revised provision of the regulations that affects package standards would include its own transitional arrangements. In this way, each change would be evaluated for its safety importance. Changes in the package standards that are important to safety would be implemented immediately upon the regulations coming into force. Other changes, that do not significantly affect safety, would have longer implementation periods. In this way, all packages in use would be compatible with the regulations in force, and no specific grandfathering provisions for older designs would be needed. NRC staff has concluded that the package design standards are mature and have been shown to be protective over the past 40 years of shipping experience. We predict that future changes in package design standards will not be substantive in terms of resulting in significant changes in physical performance of a package in transport, including actual transportation accidents. The benefits of the new system would be a more predictable regulatory structure

13 CFR 108.140 - SBA approval of initial Management Expenses.

Science.gov (United States)

2010-01-01

... VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Organizing A Nmvc Company § 108.140 SBA approval of initial Management Expenses. A NMVC Company must have its Management Expenses approved by SBA at the time of designation as a NMVC Company. (See § 108.520 for the definition of Management...

Research ethics board approval for an international thromboprophylaxis trial.

Science.gov (United States)

Lutz, Kristina; Wilton, Kelly; Zytaruk, Nicole; Julien, Lisa; Hall, Richard; Harvey, Johanne; Skrobik, Yoanna; Vlahakis, Nicholas; Meade, Laurie; Matte, Andrea; Meade, Maureen; Burns, Karen; Albert, Martin; Cash, Bronwyn Barlow; Vallance, Shirley; Klinger, James; Heels-Ansdell, Diane; Cook, Deborah

2012-06-01

Research ethics board (REB) review of scientific protocols is essential, ensuring participants' dignity, safety, and rights. The objectives of this study were to examine the time from submission to approval, to analyze predictors of approval time, and to describe the scope of conditions from REBs evaluating an international thromboprophylaxis trial. We generated survey items through literature review and investigators' discussions, creating 4 domains: respondent and institutional demographics, the REB application process, and alternate consent models. We conducted a document analysis that involved duplicate assessment of themes from REB critique of the protocol and informed consent forms (ICF). Approval was granted from 65 REB institutions, requiring 58 unique applications. We analyzed 44 (75.9%) of 58 documents and surveys. Survey respondents completing the applications had 8 (5-12) years of experience; 77% completed 4 or more REB applications in previous 5 years. Critical care personnel were represented on 54% of REBs. The time to approval was a median (interquartile range) of 75 (42, 150) days, taking longer for sites with national research consortium membership (89.1 vs 31.0 days, P = .03). Document analysis of the application process and ICF yielded 5 themes: methodology, data management, consent procedures, cataloguing, and miscellaneous. Protocol-specific themes focused on trial implementation, external critiques, and budget. The only theme specific to the ICF was risks and benefits. The most frequent comments on the protocol and ICF were about methodology and miscellaneous issues; ICF comments also addressed study risks and benefits. More studies on methods to enhance efficiency and consistency of the REB approval processes for clinical trials are needed while still maintaining high ethical standards. Copyright © 2012 Elsevier Inc. All rights reserved.

Procedure for getting safety classed concrete structures approved by Finnish Radiation and Nuclear Safety Authority

International Nuclear Information System (INIS)

Halme, Ville-Juhani

2015-01-01

Posiva is preparing geological final disposal in the Finnish bedrock in Olkiluoto, Eurajoki. The final disposal facility includes encapsulation plant and underground repository. Most of the main civil structures are concrete structures. STUK is the supervising authority in civil structures. The National Building Code of Finland and STUK's Regulatory Guide on nuclear safety (YVL) are the most important instructions when constructing concrete structures into nuclear installation. Posiva has classified concrete structures in two classes according STUK's YVL-guidance: EYT (non-nuclear) and Safety Class 3 (SC 3, nuclear safety significance). When building SC 3 concrete structures, specific protocol must be followed. Protocol includes planned routines for design, construction, supervision, quality control (QC) and quality assurance (QA) activities. Documents relating concrete structures must be approved by Posiva and STUK before construction work. After structures have been designed and actual building is ongoing, there are two main steps. Before concreting, readiness inspection for concreting must be arranged. Readiness inspection will be arranged according to a specific plan and the date must be informed to STUK. After establishing readiness for concreting, casting work can begin. Once concrete structures are done, inspected and approved, final documentation according to a quality control plan will be reviewed by Posiva. After Posiva's approval, final documentation will be sent for STUK's approval. In the end STUK will give the permission for commissioning of the concrete structures after approved commissioning inspection. The document is made up of an abstract and a poster

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

Science.gov (United States)

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

2018-05-22

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

The Energy Regulatory Commission. The Regulation of Natural Gas in Mexico

International Nuclear Information System (INIS)

1995-01-01

In May of 1995 the Congress approved amendments to the Regulatory Law of Constitutional article 27 on Petroleum. This legal reform fundamentally redefined the petroleum industry and authorizes the private sector to construct, operate, and own natural gas transportation, storage and distribution systems-activities previously reserved to the state. To complement these reforms and to implement the legislative mandate of the Regulatory Law on Petroleum, the Natural Gas Regulation (Reglamento de Gas Natural) was issued in November 1995. The regulation reconciles the interests of the various natural gas industry participants and signifies a Federal Commitment to promote comprehensive development of the industry. In parallel with the development of the substantive legal framework, the law of the Comision Reguladora de Energia (CRE) was also enacted by Congress in October 1995 to strength the institutional framework and implemented the legal changes. This law defines the CRE as an agency of the Energy Ministry with technical, operational, and budgetary autonomy, and responsibility for implementing natural gas industry regulation. (Author)

[Reporting ethics board approval in German medical theses and journals].

Science.gov (United States)

Zenz, Michael; Zenz, Julia; Grieger, Maximilian

2018-06-05

Since 1975, the Declaration of Helsinki of the World Medical Association (WMA) has clearly required ethics committee approval for research into humans. Nevertheless, this Declaration is violated quite often. As many English-language publications have addressed the theme of ethics board approval in theses and other published works, it is now to be investigated in Germany for the first time.From 2013 to 2014, a total of 1,482 medical theses at four selected universities in addition to three German-language scientific journals were reviewed. In 543 theses, reference to ethics approval would have been required according to the criteria of the Declaration of Helsinki.However, ethics approval was stated in only 58.7% of cases, and even less frequently if the prevailing doctoral regulations or instructions did not refer to the necessity of obtaining ethics approval. Theses on pediatrics mentioned ethics approval most frequently (78.6%), whereas the proportion of surgical papers was the lowest (34.9%). Among the journals, Der Nervenarzt mentioned ethics approval most frequently (59.4%) and Der Chirurg least frequently (30%).Our results point to significant deficits in mentioning ethics approval in medical theses and publications. These deficits could easily be compensated for by a thorough approach of the referees of doctoral regulations and by journal reviewers and editors.

Clinical trial transparency update: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved in Europe in 2014.

Science.gov (United States)

Deane, Bryan R; Porkess, Sheuli

2018-07-01

The objective of this study was to assess the timely disclosure of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) during 2014. This is the final extension of three previously reported studies of trials related to all new medicines approved in Europe in 2009, 2010 and 2011, and in 2012 and 2013. The original study found that over a three-year period over three-quarters of all trials were disclosed within 12 months and almost 90% were disclosed by the end of the study (31 January 2013). The extension studies (2012 and 2013 approvals) both showed an improvement in results disclosure within 12 months to 90%, and an overall disclosure rate of 92% and 93% respectively by the end of the studies. The methodology used was exactly as previously reported. Various publicly available information sources were searched for both clinical trial registration and disclosure of results. All completed company-sponsored trials related to each new medicine approved for marketing by the EMA in 2014, carried out in patients and recorded on a clinical trials registry and/or included in an EMA European Public Assessment Report (EPAR), were included. Information sources were searched between 1 May and 31 July 2016. The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 July 2016 (end of survey). Of the completed trials associated with 32 new medicines licensed to 22 different companies in 2014, results of 93% (505/542) had been disclosed within 12 months, and results of 96% (518/542) had been disclosed by 31 July 2016. The disclosure rate within 12 months of 93% suggests that industry is continuing to achieve disclosure in a timely manner. The overall disclosure rate at study end of 96% indicates that the improvement in transparency

Practice of Regulatory Science (Development of Medical Devices).

Science.gov (United States)

Niimi, Shingo

2017-01-01

Prototypes of medical devices are made in accordance with the needs of clinical practice, and for systems required during the initial process of medical device development for new surgical practices. Verification of whether these prototypes produce the intended performance specifications is conducted using basic tests such as mechanical and animal tests. The prototypes are then improved and modified until satisfactory results are obtained. After a prototype passes through a clinical trial process similar to that for new drugs, application for approval is made. In the approval application process, medical devices are divided into new, improved, and generic types. Reviewers judge the validity of intended use, indications, operation procedures, and precautions, and in addition evaluate the balance between risk and benefit in terms of efficacy and safety. Other characteristics of medical devices are the need for the user to attain proficiency in usage techniques to ensure efficacy and safety, and the existence of a variety of medical devices for which assessment strategies differ, including differences in impact on the body in cases in which a physical burden to the body or failure of a medical device develops. Regulatory science of medical devices involves prediction, judgment, and evaluation of efficacy, safety, and quality, from which data result which can become indices in the development stages from design to application for approval. A reduction in the number of animals used for testing, improvement in efficiency, reduction of the necessity for clinical trials, etc. are expected through rational setting of evaluation items.

French regulatory approach to establishing the safety case for ageing NPP`s

Energy Technology Data Exchange (ETDEWEB)

Delage, M.

1994-06-15

The French regulatory procedures make provision for three main stages in the safety assessment of nuclear power plants. The first stage ends up with the construction licence and focuses on the assessment of the preliminary safety report. The second stage makes it possible to issue the fuel loading approval following evaluation of the provisional safety report. The third stage permits to declare the start of normal operation of the installation. The procedure, the tests and the assessment forming the overall strategy for safety regulations are described in detail. (R.P.).

Analysis of Regional Timelines To Set Up a Global Phase III Clinical Trial in Breast Cancer: the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Experience

OpenAIRE

Metzger-Filho, Otto; Azambuja, Evandro de; Bradbury, Ian; Saini, Kamal S.; Bines, Jose; Simon, Sergio D. [UNIFESP; Van Dooren, Veerle; Aktan, Gursel; Pritchard, Kathleen I.; Wolff, Antonio C.; Smith, Ian; Jackisch, Christian; Lang, Istvan; Untch, Michael; Boyle, Frances

2013-01-01

Purpose. This study measured the time taken for setting up the different facets of Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO), an international phase III study being conducted in 44 participating countries.Methods. Time to regulatory authority (RA) approval, time to ethics committee/institutional review board (EC/IRB) approval, time from study approval by EC/IRB to first randomized patient, and time from first to last randomized patient were prospectively collected i...

Performance-based, cost- and time-effective PCB analytical methodology

International Nuclear Information System (INIS)

Alvarado, J. S.

1998-01-01

Laboratory applications for the analysis of PCBs (polychlorinated biphenyls) in environmental matrices such as soil/sediment/sludge and oil/waste oil were evaluated for potential reduction in waste, source reduction, and alternative techniques for final determination. As a consequence, new procedures were studied for solvent substitution, miniaturization of extraction and cleanups, minimization of reagent consumption, reduction of cost per analysis, and reduction of time. These new procedures provide adequate data that meet all the performance requirements for the determination of PCBs. Use of the new procedures reduced costs for all sample preparation techniques. Time and cost were also reduced by combining the new sample preparation procedures with the power of fast gas chromatography. Separation of Aroclor 1254 was achieved in less than 6 min by using DB-1 and SPB-608 columns. With the greatly shortened run times, reproducibility can be tested quickly and consequently with low cost. With performance-based methodology, the applications presented here can be applied now, without waiting for regulatory approval

Deciphering RNA regulatory elements in trypanosomatids: one piece at a time or genome-wide?

Science.gov (United States)

Gazestani, Vahid H; Lu, Zhiquan; Salavati, Reza

2014-05-01

Morphological and metabolic changes in the life cycle of Trypanosoma brucei are accomplished by precise regulation of hundreds of genes. In the absence of transcriptional control, RNA-binding proteins (RBPs) shape the structure of gene regulatory maps in this organism, but our knowledge about their target RNAs, binding sites, and mechanisms of action is far from complete. Although recent technological advances have revolutionized the RBP-based approaches, the main framework for the RNA regulatory element (RRE)-based approaches has not changed over the last two decades in T. brucei. In this Opinion, after highlighting the current challenges in RRE inference, we explain some genome-wide solutions that can significantly boost our current understanding about gene regulatory networks in T. brucei. Copyright © 2014 Elsevier Ltd. All rights reserved.

Can modeling of health outcomes facilitate regulatory decision making? The benefit-risk tradeoff for rosiglitazone in 1999 vs. 2007.

Science.gov (United States)

Cross, J T; Veenstra, D L; Gardner, J S; Garrison, L P

2011-03-01

Rosiglitazone was initially approved for type 2 diabetes monotherapy. We tested health-outcomes modeling as an aid to regulatory decision making by quantifying the incremental net benefit (INB) value of rosiglitazone (relative to a comparator), both at the time of first approval (1999) and at the FDA advisory committee review (2007). Using 1999 data, rosiglitazone was projected to provide an additional 0.639 years of life (0.373 quality-adjusted life years (QALYs)) relative to placebo but a loss of 0.312 years (0.173 QALYs) relative to glyburide, with uncertainty in reduction of hemoglobin A(1c) (HbA(1c)) level having the greatest impact on the benefit-risk profile. By 2007, rosiglitazone was projected to provide an additional 0.222 years (0.091 QALYs) vs. glyburide and 0.026 years vs. metformin (0.009 QALYs). Modeling suggested that the use of rosiglitazone as monotherapy was not initially warranted, given the uncertainty with regard to benefit. Despite similar net benefit (NB) as metformin shown in postmarketing data, residual cardiovascular (CV) concerns did not support the use of rosiglitazone as first-line therapy. We adapted a mathematical diabetes model to estimate NB and uncertainty of diabetes monotherapy.

A quantitative and dynamic model of the Arabidopsis flowering time gene regulatory network.

Directory of Open Access Journals (Sweden)

Felipe Leal Valentim

Full Text Available Various environmental signals integrate into a network of floral regulatory genes leading to the final decision on when to flower. Although a wealth of qualitative knowledge is available on how flowering time genes regulate each other, only a few studies incorporated this knowledge into predictive models. Such models are invaluable as they enable to investigate how various types of inputs are combined to give a quantitative readout. To investigate the effect of gene expression disturbances on flowering time, we developed a dynamic model for the regulation of flowering time in Arabidopsis thaliana. Model parameters were estimated based on expression time-courses for relevant genes, and a consistent set of flowering times for plants of various genetic backgrounds. Validation was performed by predicting changes in expression level in mutant backgrounds and comparing these predictions with independent expression data, and by comparison of predicted and experimental flowering times for several double mutants. Remarkably, the model predicts that a disturbance in a particular gene has not necessarily the largest impact on directly connected genes. For example, the model predicts that SUPPRESSOR OF OVEREXPRESSION OF CONSTANS (SOC1 mutation has a larger impact on APETALA1 (AP1, which is not directly regulated by SOC1, compared to its effect on LEAFY (LFY which is under direct control of SOC1. This was confirmed by expression data. Another model prediction involves the importance of cooperativity in the regulation of APETALA1 (AP1 by LFY, a prediction supported by experimental evidence. Concluding, our model for flowering time gene regulation enables to address how different quantitative inputs are combined into one quantitative output, flowering time.

Environmental approvals in New Brunswick : economic considerations

Energy Technology Data Exchange (ETDEWEB)

Marrack, C.; Maitland, R. [Suez Renewable Energy North America, Houston, TX (United States)

2008-07-01

This presentation provided a timeline of economic considerations related to New Brunswick's regulatory approval process for wind power developments. The economics of wind power projects require careful consideration during the initial planning phases, as it is not yet known if projects are viable. Spending in the early stages of a project should therefore be limited to items that focus on components of the environmental impact assessment (EIA) process that include establishing a relationship with First Nations groups in the area, and conducting seasonal bird studies. Economic considerations change when project viability is confirmed, and developers can then progress to conducting traditional knowledge studies and further seasonal bird studies. Baseline information studies should be reviewed, and biophysical surveys should involve the identification of any wetlands, sensitive areas, and rare plants. Archaeology studies are also required by the provincial government, as well as bat studies to determine if the site has a resident population of bats. Public and stakeholder consultations and open houses should then be held with an adequate time-frame for the submission of questions and concerns and the development of mitigation strategies. Project viability should be confirmed before power purchase agreements (PPAs) are signed. After PPAs are signed, the largest economic consideration is the schedule-related risk associated with legal and financial problems. It was concluded that noise impact, visual impact, and socioeconomic assessments and studies can be conducted after the PPA is secured. tabs., figs.

Resolution 127/012. It approve the fuel quality 50-S Oil Gas characteristics within the framework of Technical Quality Specifications Rules for liquid fuel

International Nuclear Information System (INIS)

2012-01-01

This resolution approves the initiative of Ancap fuel quality 50-S Oil Gas characteristics within the framework of Technical Quality Specifications Rules for liquid fuel. This resolution is according to the opinion of the National Energy Regulatory Unit and the Energy and Water Services in relation with the requirements of the current rule.

[Collaborative projects with academia for regulatory science studies on biomarkers].

Science.gov (United States)

Saito, Yoshiro; Nakamura, Ryosuke; Maekawa, Keiko

2014-01-01

Biomarkers are useful tools to be utilized as indicators/predictors of disease severity and drug responsiveness/safety, and thus are expected to promote efficient drug development and to accelerate proper use of approved drugs. Many academic achievements have been reported, but only a small number of biomarkers are used in clinical trials and drug treatments. Regulatory sciences on biomarkers for their secure development and proper qualification are necessary to facilitate their practical application. We started to collaborate with Tohoku University and Nagoya City University for sample quality, biomarker identification, evaluation of their usage, and making guidances. In this short review, scheme and progress of these projects are introduced.

Regulatory aspects on underground disposal of radioactive waste in Sweden

International Nuclear Information System (INIS)

Larsson, A.

1978-01-01

The underground disposal of radioactive waste in Sweden is primarily governed by the Atomic Energy Act, the Radiation Protection Act, and to some extent by the Nuclear Liability Act. The regulatory authorities in question are the Nuclear Power Inspectorate, and the Radiation protection Institute. Application for a licence relating to waste management facilities are examined by the Inspectorate which presents its recommendations to the Government for decision. The Inspectorate is also called upon to impose conditions for the operation of the installation. The choice of site for the proposed nuclear waste facility is subject to the approval of the local authorities concerned. (NEA) [fr

Regulatory perspectives of concept assessment

International Nuclear Information System (INIS)

Flavelle, Peter A.

1987-09-01

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

Redfield Energy Approval

Science.gov (United States)

This September 19, 2016 letter from EPA approves the petition from Poet Biorefining-Lake Crystal, regarding non-This October 27, 2016 letter from EPA approves the petition from Redfield Energy, LLC, regarding non-grandfathered ethanol produced

Regulatory Approach to Safety of Long Time Operating Research Reactors in Russia

Energy Technology Data Exchange (ETDEWEB)

Sapozhnikov, Alexander [Industrial and Nuclear Supervision Service, Moscow (Russian Federation)

2013-07-01

In the Russian Federation more than 60% of operating Nuclear Research Facilities (NRFs) are of age over 30 years old or their usage exceeds originally conceived continuous operation. In this regard, important areas of regulatory body activity are: 1) a systematic assessment of the actual state of structures, systems and components (SSCs) important to safety, 2) control of implementation of organizational and technical measures to mitigate ageing impact on the basis of programmes to manage reliability (service life) of SSCs, and 3) issues of facility modification/reconstruction in line with up-to-day safety requirements. The practice of licensing NRFs with long operating times shows that the national regulations are generally in compliance with IAEA recommendations for ageing management of research reactors. In operating organizations, the ageing management is being effectively provided as a part of the integrated management system for NRFs, including the monitoring of the reliability of SSCs, a methodology to detect their ageing, reporting and investigation of events, analysis of their root causes, and measures to prevent and mitigate ageing effects to safety. The report outlines a good practice of safety regulation of NRFs with long operating times and based on lessons learned from experience, including challenges for future improvement of ageing management.

Regulatory Approach to Safety of Long Time Operating Research Reactors in Russia

International Nuclear Information System (INIS)

Sapozhnikov, Alexander

2013-01-01

In the Russian Federation more than 60% of operating Nuclear Research Facilities (NRFs) are of age over 30 years old or their usage exceeds originally conceived continuous operation. In this regard, important areas of regulatory body activity are: 1) a systematic assessment of the actual state of structures, systems and components (SSCs) important to safety, 2) control of implementation of organizational and technical measures to mitigate ageing impact on the basis of programmes to manage reliability (service life) of SSCs, and 3) issues of facility modification/reconstruction in line with up-to-day safety requirements. The practice of licensing NRFs with long operating times shows that the national regulations are generally in compliance with IAEA recommendations for ageing management of research reactors. In operating organizations, the ageing management is being effectively provided as a part of the integrated management system for NRFs, including the monitoring of the reliability of SSCs, a methodology to detect their ageing, reporting and investigation of events, analysis of their root causes, and measures to prevent and mitigate ageing effects to safety. The report outlines a good practice of safety regulation of NRFs with long operating times and based on lessons learned from experience, including challenges for future improvement of ageing management

Streamlining the Capstone Process: A Time-Saving Approval System for Graduate Theses/Projects

Science.gov (United States)

Grooms, James; Kline, Douglas; Cummings, Jeffrey

2016-01-01

Capstones have become an integral part of many information systems programs, both at the undergraduate and graduate level. One of the challenges can be tracking the process from the start of the capstone to completion. This paper describes the analysis, design and implementation of a web application for the approval workflow of a master's program…

The major cellular sterol regulatory pathway is required for Andes virus infection.

Directory of Open Access Journals (Sweden)

Josiah Petersen

2014-02-01

Full Text Available The Bunyaviridae comprise a large family of RNA viruses with worldwide distribution and includes the pathogenic New World hantavirus, Andes virus (ANDV. Host factors needed for hantavirus entry remain largely enigmatic and therapeutics are unavailable. To identify cellular requirements for ANDV infection, we performed two parallel genetic screens. Analysis of a large library of insertionally mutagenized human haploid cells and a siRNA genomic screen converged on components (SREBP-2, SCAP, S1P and S2P of the sterol regulatory pathway as critically important for infection by ANDV. The significance of this pathway was confirmed using functionally deficient cells, TALEN-mediated gene disruption, RNA interference and pharmacologic inhibition. Disruption of sterol regulatory complex function impaired ANDV internalization without affecting virus binding. Pharmacologic manipulation of cholesterol levels demonstrated that ANDV entry is sensitive to changes in cellular cholesterol and raises the possibility that clinically approved regulators of sterol synthesis may prove useful for combating ANDV infection.

Managing risk in developing transplant immunosuppressive agents: the new regulatory environment.

Science.gov (United States)

Gabardi, S; Halloran, P F; Friedewald, J

2011-09-01

Recent adverse experience with a number of medications after their approval, including rofecoxib, erythropoietin and rosiglitazone, has led to an increased focus on safety in drug development in the postmarketing setting. The result was implementation of new measures to address perceived deficits in the system for drug approval and postmarketing safety. The resulting legislation introduced risk evaluation and mitigation strategies (REMS) and postmarketing requirements (PMRs). Although these initiatives have the potential to improve patient outcomes, many healthcare practitioners are not yet familiar with REMS or PMRs or may have misconceptions regarding their goals and limitations. REMS is a program to manage known or potential serious risks associated with pharmaceutical products and is designed to ensure that the benefits of using a particular product outweigh the risks. Although the concepts underlying REMS and PMRs are not novel, the FDA now has legal authority to enforce such measures as part of the drug approval process. This article outlines the objectives and limitations of REMS and PMRs, with a focus on how these regulatory measures may impact the clinical specialty of transplantation. The article also briefly describes efforts to address aspects of drug safety less amenable to management through REMS and PMRs. © 2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Actions of the Cuban Nuclear Regulatory Authority in the adequate implementation of the legislation in matter of radiological protection

International Nuclear Information System (INIS)

Fornet R, O.M.; Guillen C, A.; Betancourt H, L.A.

2006-01-01

The effectiveness of the regulatory activity in matter of safety and radiological protection it depends in great measure of the practical implementation level of the legislation in this matter. In our country this objective has been achieved through the one continuous improvement of the Hierarchical System of Nuclear Regulation, the reconciliation with specialists and national experts in each matter during the elaboration of the legal documents; the popularization and gratuitous distribution of it approved; the precision in the validation conditions of the authorizations of those main precepts applicable to the practices; the legal foundation of the deficiencies evidenced in the regulatory inspections; the development of a Safety Culture; the realization of Annual Regulatory Conferences and mainly in the training of the personnel related with the safety. Also, the constant analysis on the part of the specialists of the Regulatory Authority of the grade of implementation of this legislation, it discussion in national and international events and the actions recommended in these works. As a result of this focus, it is considered that the Regulatory Authority has impacted appropriately in the implementation of this legislation. (Author)

30 CFR 18.95 - Approval of machines constructed of components approved, accepted or certified under Bureau of...

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Approval of machines constructed of components... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Field Approval of Electrically Operated Mining Equipment § 18.95 Approval of machines constructed of components approved...

Mexico's Regulatory Engagement in Bulk Electric Power System Planning: An Overview of U.S. Practices and Tools

Energy Technology Data Exchange (ETDEWEB)

O' Neill, Barbara; Hurlbut, David; Pena, Ivonne; Gagne, Douglas; Cook, Jeff; Bracho, Ricardo

2016-06-01

Mexico's transition to a modern wholesale power market will place new demands on how regulators evaluate and approve transmission expansion projects. Transmission projects in a modern wholesale market fulfill one of several needs, and utilities, regional transmission organizations, and regulatory authorities in the United States have encountered comparable challenges in their market transitions to ensure projects meeting each type of need can be built. The purpose of this report is to open a window to view that experience. The report examines key practices of different U.S. jurisdictions that have moved from transmission planning to transmission approval, and it focuses on the role of the regulator in supporting a planning process that equitably meets identified needs.

The impact of regulatory obligations on fishers’ income

DEFF Research Database (Denmark)

Hadjimichael, Maria; J. Kaiser, Michel; Edwards-Jones, Gareth

2013-01-01

as a marketing tool to identify fishers’ most and least preferred regulatory obligations in terms of the impact these obligations have on their income. Significant differences were identified in fishers’ preferences that depended on the regulatory measures fishers operated under at the time of the study (which...

The Regulatory Independence of FANR

International Nuclear Information System (INIS)

ALNuaimi, Fatema; Choi, Kwang Shik

2012-01-01

Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

The Regulatory Independence of FANR

Energy Technology Data Exchange (ETDEWEB)

ALNuaimi, Fatema; Choi, Kwang Shik [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2012-05-15

Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

Data Management in a Regulatory Context

Directory of Open Access Journals (Sweden)

Niels Grønning

2017-07-01

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

3 CFR - Regulatory Review

Science.gov (United States)

2010-01-01

... as a means of promoting regulatory goals. The fundamental principles and structures governing... review. In this time of fundamental transformation, that process—and the principles governing regulation... the Office of Management and Budget (OMB) has reviewed Federal regulations. The purposes of such...

Physical protection of shipments of irradiated reactor fuel; Interim guidance. Regulatory report

International Nuclear Information System (INIS)

1980-06-01

During May, 1979, the U.S. Nuclear Regulatory Commission approved for issuance in effective form new interim regulations for strengthening the protection of spent fuel shipments against sabotage and diversion. The new regulations were issued without benefit of public comment, but comments from the public were solicited after the effective date. Based upon the public comments received, the interim regulations were amended and reissued in effective form as a final interim rule in May, 1980. The present document supersedes a previously issued interim guidance document, NUREG-0561 (June, 1979) which accompanied the original rule. This report has been revised to conform to the new interim regulations on the physical protection of shipments of irradiated reactor fuel which are likely to remain in effect until the completion of an ongoing research program concerning the response of spent fuel to certain forms of sabotage, at which time the regulations may be rescinded, modified or made permanent, as appropriate. This report discusses the amended regulations and provides a basis on which licensees can develop an acceptable interim program for the protection of spent fuel shipments

Drugs Approved for Breast Cancer

Science.gov (United States)

... Ask about Your Treatment Research Drugs Approved for Breast Cancer This page lists cancer drugs approved by the ... are not listed here. Drugs Approved to Prevent Breast Cancer Evista (Raloxifene Hydrochloride) Raloxifene Hydrochloride Tamoxifen Citrate Drugs ...

Regulatory activities

International Nuclear Information System (INIS)

2001-01-01

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

Power plant construction contracting in a changing regulatory environment

International Nuclear Information System (INIS)

Person, J.C.

1993-01-01

The 1965 blackout in the Northeast provided the wake-up call that spawned in unprecedented program of power plant construction by electric utilities. This building program began in the late 1960s and continued unabated through the 1970s. Beginning in the late 1970s, state regulators began in era of 'prudence' reviews which disallowed as imprudent significant portions of the costs of certain nuclear units being brought on line at the time. This regulatory experience brought about a fundamental change in the way in which utilities evaluated the need for additional capacity. This paper explores construction contracting trends in light of recent developments in the relationship between the electric utility and the state regulator. It is within this context that the utility decides: (1) whether to build, buy, or save; and (2) if the decision is to build, which project planning and administration considerations will maximize the utility's ability to incorporate project costs into the ratebase. In order to put these issues into their proper perspective, this paper first presents a brief overview of the prudence decisions of the past, and the chilling effect of these decisions generally on new project planning. The paper next focuses on the recent changes to the post-construction prudence review model, including the introduction of pre-approval arrangements and rolling prudence reviews. Following that will be a survey of new construction spending decisions in light of these changes. After an analysis of the bases for the prudence disallowances of the past and the application of the lessons learned from these disallowances to contract planning and administration issues of today, the paper will close with a discussion of the relative advantages and disadvantages of the most commonly used contract delivery methods in today's regulatory environment

Drugs Approved for Thyroid Cancer

Science.gov (United States)

... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) Doxorubicin ...

Regulatory T Cells: Potential Target in Anticancer Immunotherapy

Directory of Open Access Journals (Sweden)

Chi-Mou Juang

2007-09-01

Full Text Available The concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor α-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cellmediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed.

Future time perspective and health behaviors: temporal framing of self-regulatory processes in physical exercise and dietary behaviors.

Science.gov (United States)

Gellert, Paul; Ziegelmann, Jochen P; Lippke, Sonia; Schwarzer, Ralf

2012-04-01

Limitations in perceived lifetime can undermine long-term goal striving. Planning is supposed to translate intentions into health behaviors and to operate as a compensatory strategy to overcome goal striving deficits associated with a limited time perspective. Two longitudinal studies were conducted examining the compensatory role of planning: an online survey on fruit and vegetable consumption (N = 909; 16-78 years; follow-up at 4 months) and a questionnaire study on physical exercise in older adults (N = 289; 60-95 years, over a half-year period). Intentions, planning, and behavior were measured in a behavior-specific, future time perspective in a generic manner. Planning mediated between intentions and both health behaviors. Time perspective operated as a moderator, indicating that in individuals with a more limited time perspective, a stronger effect of planning on health behaviors emerged. Planning as a self-regulatory strategy may compensate for a limited time perspective.

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

Directory of Open Access Journals (Sweden)

Janis eAncans

2012-08-01

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

Organization of nuclear regulatory activities

International Nuclear Information System (INIS)

Blidaru, Valentin

2008-01-01

The paper presents the structure, missions and organizational aspects of the CNCAN, the National Commission for the control of nuclear activities in Romania. The paper addresses the following main issues: 1.General aspects; 2.Organizational structure of the NRA in Romania; 3.General description of the Division for Nuclear Safety Assessments; 4.Specific activities; 5.Regulatory approaches and practices. Under the title of 'General aspects' the following three basic statements are highlighted: 1.CNCAN is a governmental organization responsible for the development of the regulatory framework, the control of its implementation and the licensing of nuclear facilities; 2.CNCAN is the national authority competent in exercising the regulatory activity, authorization and control in the nuclear field provided by the law No. 111/ 1996 republished in 1998; 3.The Commission exercises its functions independently of the ministries and other authorities of the public control administration being subordinated to the Romanian Government. The organizational structure is as follows: - President, the Managerial Council and the Advisory Council coordinating the four General Divisions that are responsible for: - Nuclear Safety with Division of Nuclear Safety Assessment and Division of Nuclear Objectives Surveillance; - Radiological Safety with Division of Radiological Safety Assessment and Division of Operational Radiation Protection; - Surveillance of Environmental Radioactivity with Division of Assessment and Analysis and Division of National Network; - Development and Resource with the Division of Economy and Division of Human Resources. In addition under direct coordination of the President operate the Division of Radiation Protection, Transport and Radioactive Waste and the Division of International Cooperation and Communication. Specific activities are listed describing among others the issues of: - Safety of nuclear installation; - Evaluation relating to licensing of nuclear

TRUPACT-II, a regulatory perspective

International Nuclear Information System (INIS)

Gregory, P.C.; Spooner, O.R.

1995-01-01

The Transuranic Package Transporter II (TRUPACT-II) is a US Nuclear Regulatory Commission (NRC) certified Type B packaging for the shipment of contact-handled transuranic (CH-TRU) material by the US Department of Energy (DOE). The NRC approved the TRUPACT-II design as meeting the requirements of Title 10, Code of Federal Regulations, Part 71 (10 CFR 71) and issued Certificate of Compliance (CofC) Number 9218 to the DOE. There are currently 15 certified TRUPACT-IIs. Additional TRUPACT-IIs will be required to make more than 15,000 shipments of CH-TRU waste to the Waste Isolation Pilot Plant (WIPP) site near Carlsbad, New Mexico. The TRUPACT-II may also be used for the DOE inter-site and intra-site shipments of CH-TRU waste. The Land Withdrawal Act (Public Law 102-579), enacted by the US Congress, October 30, 1992, and an agreement between the DOE and the State of New Mexico, signed August 4, 1987, both stipulate that only NRC approved packaging may be used for shipments of TRU waste to the WIPP. Early in the TRUPACT-II development phase it was decided that the transportation system (tractor, trailer, and TRUPACT-II) should be highway legal on all routes without the need for oversize and/or overweight permits. In large measure, public acceptance of the DOE's efforts to safely transport CH-TRU waste depends on the public's perception that the TRUPACT-II is in compliance with all applicable regulations, standards, and quality assurance requirements. This paper addresses some of the numerous regulations applicable to Type B packaging, and it describes how the TRUPACT-II complies with these regulations

Review of NRC Commission Papers on Regulatory Basis for Licensing and Regulating Reprocessing Facilities

Energy Technology Data Exchange (ETDEWEB)

Park, Jae Yeong; Shin, Hyeong Ki [KINS, Daejeon (Korea, Republic of)

2016-05-15

Spent nuclear fuel (SNF) accumulated in nuclear power plant has been a serious issue in most countries with operating nuclear power plants. Direct disposal of SNF could be a solution of the problem but many countries including the Republic of Korea have had a hard time selecting a site for high level waste repository because of low public acceptance. SNF recycling technologies consisting of reprocessing and transmutation have been developed so as to reduce the final volume of the disposed radioactive waste and to diminish the radiotoxicity of the waste. The Republic of Korea is now developing pyroprocessing and sodium-cooled fast reactor (SFR) technology to be used for the recycling of the wastes. KAERI has a plan to construct a pyroprocessing facility with a capacity of 30 tHM/y and a facility manufacturing TRU fuel for SFR by 2025. However, to license these facility and secure the safety, the current regulatory system related to SNF treatment needs to be improved and amended since the system has been developed focusing on facilities to examine irradiated nuclear materials. Status of reprocessing facility regulations developed by U.S.NRC was reviewed based on SECY papers. U.S.NRC has approved the development of a new rule referred to nationally as '10CFR Part 7x'. Existing 10CFR 50 and 70 has been evolved mainly for nuclear power plants and fuel cycle facilities whose radiological hazard is much lower than reprocessing plants respectively. U.S.NRC also derived many regulatory gaps including safety assessment methods, technical specification, general design criteria and waste classification and continue to develop the regulatory framework limited in scope to the resolution of Gap 5.

Regulatory compliance issues related to the White Oak Creek Embayment time-critical removal action

International Nuclear Information System (INIS)

Leslie, M.; Kimmel, B.L.

1991-01-01

In September 1990, Martin Marietta Energy Systems (Energy Systems) discovered high levels of Cesium-137 ( 137 Cs) in surface sedimenus near the mouth of White Oak Creek Embayment (WOCE). White Oak Creek (WOC) receives surface water drainage from Oak Ridge National Laboratory. Since this discovery, the Department of Energy (DOE) and Energy Systems have pursued actions designed to stabilize the contaminated WOCE sediments under provisions of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA), and the implementing regulations in the National Contingency Plan (NCP) (40 CFR Part 300), as a time-critical removal action. By definition, a time-critical removal is an action where onsite activities are initiated within six months of the determination that a removal action is appropriate. Time-critical removal actions allow comparatively rapid mobilization to protect human health and the environment without going through the lengthy and extensive CERCLA Remedial Investigation/Feasibility Study/Record of Decision process. Many aspects of the project, in terms of compliance with the substantive requirements of the NCP and ARARs, have exceeded the regulatory requirements, despite the fact that there is no apparent authority on conducting removal actions at Federal facilities. Much of the interpretation of the NCP was groundbreaking in nature for both EPA and DOE. 4 refs., 2 figs

Nuclear regulatory regime in Lithuania

International Nuclear Information System (INIS)

Kutas, S.

1999-01-01

The Law on Nuclear Energy establishes the legal basis for nuclear safety in the Republic of Lithuania. It assigns the responsibility for safety to the operating organization of a nuclear facility and outlines the tasks of the operator and the regulatory authority. According to this Law, the Nuclear Power Safety Inspectorate (VATESI) shall implement state regulation of nuclear safety. Standards and rules, guides and regulations of nuclear safety and radiation protection approved by the Government or by the institutions authorised. It is mandatory for all public and local authorities, enterprises, institutions, organisations, their associations, the officials and other persons whose activities are related to the operation of nuclear facilities, to the use and management of nuclear and radioactive materials therein. Safety guarantee in nuclear energy based on the requirements of the laws and regulations of the Republic of Lithuania, on the requirements of the international treaties to which the Republic of Lithuania is a party, also on the recommendations of the IAEA and other international organisations and authorities

Politically Induced Regulatory Risk and Independent Regulatory Agencies

OpenAIRE

Strausz, Roland

2015-01-01

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

A big data pipeline: Identifying dynamic gene regulatory networks from time-course Gene Expression Omnibus data with applications to influenza infection.

Science.gov (United States)

Carey, Michelle; Ramírez, Juan Camilo; Wu, Shuang; Wu, Hulin

2018-07-01

A biological host response to an external stimulus or intervention such as a disease or infection is a dynamic process, which is regulated by an intricate network of many genes and their products. Understanding the dynamics of this gene regulatory network allows us to infer the mechanisms involved in a host response to an external stimulus, and hence aids the discovery of biomarkers of phenotype and biological function. In this article, we propose a modeling/analysis pipeline for dynamic gene expression data, called Pipeline4DGEData, which consists of a series of statistical modeling techniques to construct dynamic gene regulatory networks from the large volumes of high-dimensional time-course gene expression data that are freely available in the Gene Expression Omnibus repository. This pipeline has a consistent and scalable structure that allows it to simultaneously analyze a large number of time-course gene expression data sets, and then integrate the results across different studies. We apply the proposed pipeline to influenza infection data from nine studies and demonstrate that interesting biological findings can be discovered with its implementation.

FERC approves process for Lake Erie link: Project meets significant regulatory milestone

International Nuclear Information System (INIS)

Anon

2002-01-01

The Federal Electric Regulatory Commission (FERC) of the United States has issued an order to TransEnergie US Ltd., and Hydro One Inc., authorizing the sale of transmission rights for the proposed Lake Erie link. This project will consists of bi-directional high voltage direct current facilities connecting the transmission grids of Ontario, Canada and the United States. The sale is authorized to proceed via a non-discriminatory 'open season' process. The project will consist of buried underwater cables under Lake Erie connecting the transmission systems near Simcoe, Ontario with those in the US at either, or both, of Springfield, Pennsylvania, and Ashtabula, Ohio. The project will provide an increase in transmission capability of up to 975 MW between the electric control areas of the Ontario Independent Electricity Market Operator, the East Central Area Reliability Coordination Agreement in Ohio and the Pennsylvania-New Jersey-Maryland Interconnection. The Lake Erie Link will be financially supported by those consumers who see value in the associated transmission rights, rather than through the regulated rates paid by transmission customers in general. The article provides an overview of the background of the Lake Erie Link, the cable system, the converter station, and the potential economic benefits

EFFECTS OF HISTONE DEACETYLASE INHIBITOR, SAHA, ON EFFECTOR AND FOXP3+ REGULATORY T CELLS IN RHESUS MACAQUES

OpenAIRE

Johnson, Jennifer; Pahuja, Anil; Graham, Melanie; Hering, Bernhard; Hancock, Wayne W.; Pratima, Bansal-Pakala

2008-01-01

SAHA, a histone deacetylase inhibitor (HDACi), is clinically approved for treatment of cutaneous T-cell lymphoma. Although the exact underlying mechanisms are unknown, HDACi arrest the cell cycle in rapidly proliferating tumor cells and promote their apoptosis. HDACi were also recently shown to enhance the production and suppressive functions of Foxp3+ regulatory T (Treg) cells in rodents, leading us to begin to investigate the actions of HDACi on rhesus monkey T cells for the sake of potenti...

77 FR 52098 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Science.gov (United States)

2012-08-28

... Exchange would announce via Regulatory Bulletin the applicable time period(s) for the Risk Limitation... Exchange would specify via Regulatory Bulletin the applicable time period(s) for the Risk Limitation... Risk Limitation Mechanisms, as well as any applicable time period(s) and order types, via Regulatory...

A materials engineering view of license renewal at the US Nuclear Regulatory Commission

International Nuclear Information System (INIS)

Banic, M.

1999-01-01

This paper discusses the treatment of license renewal at the US Nuclear Regulatory Commission (NRC) with emphasis on the review process by the staff of the Materials and Chemical Engineering Branch (EMCB). The paper covers the rules governing license renewal, the applications received, the schedule, the approach, and the technical issues. The NRC has a tight schedule of 30-36 months to renew a license. To date, Baltimore Gas and Electric (BG and E) and Duke Power have applied for license renewal. Expecting more applicants, the staff has taken steps to address the public's concern that the effects of aging will be adequately managed and the industry's concern that the reviews will be timely, efficient, and uniform. These steps include identifying aging effects and making the results available in a report and computerized database, approving topical reports and aging management programs for generic use, and reviewing aging management programs according to specific criteria. Materials Engineering staff have a major role because many of the aging issues are materials related. (author)

Regulatory policies for using oil dispersants in the Barents Sea

Directory of Open Access Journals (Sweden)

Natalia Belkina

2015-04-01

Full Text Available Use of dispersants requires assessment of which environmental values are at stake. In the Barents Sea this issue is of high concern as large oil spills can cause transboundary pollution, affecting the interests of two neighbouring countries. The Joint Contingency Plan in the Barents Sea does not set any specific requirements for use of dispersants and lets Norway and Russia follow their national procedures. The Plan emphasizes that in case of transboundary pollution the decision to use dispersants shall only be undertaken upon common agreement. The paper presents a comparison of the national regulatory approaches of Norway and Russia to using dispersants. The research is based on the analysis of legislative documents and interviews with oil companies, oil spill responders and relevant national authorities. The research reveals that in both countries use of dispersants requires preliminary authorization of the national agencies. In Norway the pre-approval procedure and the algorithm of dispersants involvement in response to a real accident are clearly documented and are regularly tested. This has made the process of approval for using dispersants more efficient. In Russia the lack of practical experience in using dispersants and well-established approval procedures can result in a long and unclear permitting process for each oil spill case. This could seriously hinder the use of dispersants to combat transboundary pollution in the Barents Sea, even if it is considered to be beneficial. We conclude that the development of a harmonized approach for dispersants use in the Barents Sea should be thoroughly assessed.

Post-approval monitoring and oversight of U.S.-initiated human subjects research in resource-constrained countries.

Science.gov (United States)

Brown, Brandon; Kinsler, Janni; Folayan, Morenike O; Allen, Karen; Cáceres, Carlos F

2014-06-01

The history of human subjects research and controversial procedures in relation to it has helped form the field of bioethics. Ethically questionable elements may be identified during research design, research implementation, management at the study site, or actions by a study's investigator or other staff. Post-approval monitoring (PAM) may prevent violations from occurring or enable their identification at an early stage. In U.S.-initiated human subjects research taking place in resource-constrained countries with limited development of research regulatory structures, arranging a site visit from a U.S. research ethics committee (REC) becomes difficult, thus creating a potential barrier to regulatory oversight by the parent REC. However, this barrier may be overcome through the use of digital technologies, since much of the world has at least remote access to the Internet. Empirical research is needed to pilot test the use of these technologies for research oversight to ensure the protection of human subjects taking part in research worldwide.

U.S. Food and Drug Administration drug approval: slow advances in obstetric care in the United States.

Science.gov (United States)

Wing, Deborah A; Powers, Barbara; Hickok, Durlin

2010-04-01

The process for drug approval in the United States is complex and time-consuming. There are comparatively few drugs with U.S. Food and Drug Administration (FDA)-approved indications for obstetric use in this country at this time; however, several are under development. We review the process for drug approval and recount the approval histories of obstetric drugs reviewed in the recent past. We also outline the current status of two progestational agents that are under development. For a variety of reasons, including a small market compared with others such as cardiology or oncology, and the potential of being drawn into medical-legal litigation, sponsors are disinclined to pursue drug development for obstetric purposes in this country. We compare the procedures for review and approval of drugs in the United States with those in Europe, and note that recent changes within the FDA may result in not only more drugs being approved but also changes in labeling of already approved drugs. Special programs to facilitate drug development and reforms to modernize the process and improve safety are discussed. These may result in changes in labeling of already approved drugs. Obstacles such as funding and liability are also discussed.

Zohydro approval by food and drug administration: controversial or frightening?

Science.gov (United States)

Manchikanti, Laxmaiah; Atluri, Sairam; Candido, Kenneth D; Boswell, Mark V; Simopoulos, Thomas T; Grider, Jay S; Falco, Frank J E; Hirsch, Joshua A

2014-01-01

The actions and regulations of the Food and Drug Administration (FDA) are crucial to the entire population of the U.S., specifically the public who take a multitude of drugs and providers who prescribe drugs and devices. Further, the FDA is relevant to investors, specifically in regards to biotech and pharmaceutical companies involved in developing new drugs. The FDA has been criticized for a lack of independence on the one hand and excessive regulatory and expanding authority without evidence and consistency of the actions on the other hand. The FDA approved a single-entity, long-acting, hydrocodone product (Zohydro, Zogenix, San Diego, CA) on October 25, 2013, against the recommendation of the FDA's own appointed scientific advisory panel, which voted 11 to 2 against the approval of Zohydro. Subsequent to the approval, multiple consumer safety organizations, health care agencies, addiction treatment providers, professional organizations, and other groups on the frontline of the opioid addiction epidemic have expressed concern. In addition, the US Congress and various state attorneys general raised serious concerns about the approval of Zohydro, which is highly addictive and may enhance the opioid addiction epidemic. Supporters of Zohydro contend that it is necessary and essential to manage chronic pain and improve functional status with no additional risk. Over the past 15 years, prescriptions for opioids have skyrocketed with the United States consuming more than 84% of the global oxycodone and more than 99% of the hydrocodone supply. The sharp increase in opioid prescribing has led to parallel increases in opioid addiction and overdose deaths, surpassing motor vehicle injuries in the U.S. Recent studies assessing the trends of medical use and misuse of opioid analgesics from 2000 to 2011 have concluded that the present trend of the continued increase in the medical use of opioid analgesics appears to contribute to increasing misuse, resulting in multiple health

Mission Risk Reduction Regulatory Change Management

Science.gov (United States)

Scroggins, Sharon

2007-01-01

NASA Headquarters Environmental Management Division supports NASA's mission to pioneer the future in space exploration, scientific discovery, and aeronautics research by integrating environmental considerations into programs and projects early-on, thereby proactively reducing NASA's exposure to institutional, programmatic and operational risk. As part of this effort, NASA established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) as a resource for detecting, analyzing, and communicating environmental regulatory risks to the NASA stakeholder community. The RRAC PC focuses on detecting emerging environmental regulations and other operational change drivers that may pose risks to NASA programs and facilities, and effectively communicating the potential risks. For example, regulatory change may restrict how and where certain activities or operations may be conducted. Regulatory change can also directly affect the ability to use certain materials by mandating a production phase-out or restricting usage applications of certain materials. Regulatory change can result in significant adverse impacts to NASA programs and facilities due to NASA's stringent performance requirements for materials and components related to human-rated space vehicles. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented a system for proactively managing regulatory change to minimize potential adverse impacts to NASA programs and facilities. This presentation highlights the process utilized by the RRACPC to communicate regulatory change and the associated

Advances on generic exemption levels and generic clearance levels in the argentinean regulatory field

International Nuclear Information System (INIS)

Muñiz, C.C.; Bossio, M.C.

2011-01-01

With the aim of optimizing the regulatory effort in Argentina, the Nuclear Regulatory Authority (ARN) evaluated two worldwide concepts used in the radioactive waste management field: “Generic Exemption Levels” and “Generic Clearance Levels”. The objective of this paper is to present the progress made in the past two years in relation to these topics and to present the results of the specific requests received from users of radioactive material. Since the approval of both Generic Levels, the ARN received two exemption requests. The first one, regarding the practice of dismantling lighting rods with 241 Am. The other case regards the international trade, distribution, usage and final disposal of lighting products with radioactive material ( 85 Kr and 232 Th). Concerning clearance, there has not been any request yet. However, in the future the ARN expects to receive this kind of requests from nuclear power plants and other facilities related to the nuclear fuel cycle. (authors) [es

Timing Is everything: quantifying regulatory and market readiness levels for technology transition policy analysis

Energy Technology Data Exchange (ETDEWEB)

Kobos, Peter Holmes [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Malczynski, Leonard A. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Walker, La Tonya Nicole [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Borns, David James [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

2014-03-01

People save for retirement throughout their career because it is virtually impossible to save all you’ll need in retirement the year before you retire. Similarly, without installing incremental amounts of clean fossil, renewable or transformative energy technologies throughout the coming decades, a radical and immediate change will be near impossible the year before a policy goal is set to be in place. This notion of steady installation growth over acute installations of technology to meet policy goals is the core topic of discussion for this research. This research operationalizes this notion by developing the theoretical underpinnings of regulatory and market acceptance delays by building upon the common Technology Readiness Level (TRL) framework and offers two new additions to the research community. The new and novel Regulatory Readiness Level (RRL) and Market Readiness Level (MRL) frameworks were developed. These components, collectively called the Technology, Regulatory and Market (TRM) readiness level framework allow one to build new constraints into existing Integrated Assessment Models (IAMs) to address research questions such as, ‘To meet our desired technical and policy goals, what are the factors that affect the rate we must install technology to achieve these goals in the coming decades?’

Robustness and accuracy in sea urchin developmental gene regulatory networks

Directory of Open Access Journals (Sweden)

Smadar eBen-Tabou De-Leon

2016-02-01

Full Text Available Developmental gene regulatory networks robustly control the timely activation of regulatory and differentiation genes. The structure of these networks underlies their capacity to buffer intrinsic and extrinsic noise and maintain embryonic morphology. Here I illustrate how the use of specific architectures by the sea urchin developmental regulatory networks enables the robust control of cell fate decisions. The Wnt-βcatenin signaling pathway patterns the primary embryonic axis while the BMP signaling pathway patterns the secondary embryonic axis in the sea urchin embryo and across bilateria. Interestingly, in the sea urchin in both cases, the signaling pathway that defines the axis controls directly the expression of a set of downstream regulatory genes. I propose that this direct activation of a set of regulatory genes enables a uniform regulatory response and a clear cut cell fate decision in the endoderm and in the dorsal ectoderm. The specification of the mesodermal pigment cell lineage is activated by Delta signaling that initiates a triple positive feedback loop that locks down the pigment specification state. I propose that the use of compound positive feedback circuitry provides the endodermal cells enough time to turn off mesodermal genes and ensures correct mesoderm vs. endoderm fate decision. Thus, I argue that understanding the control properties of repeatedly used regulatory architectures illuminates their role in embryogenesis and provides possible explanations to their resistance to evolutionary change.

A Review on Regulatory Enforcement Policy

International Nuclear Information System (INIS)

Lim, Ji Han; Lee, Kyung Joo; Choi, Young Sung

2017-01-01

This paper examine the meaning and principle of enforcement through examples from other countries. Regulatory enforcement is the last stage of safety regulation and how it is exercised when one failing to meet regulatory requirements can have significant ripple effect across the industry. Thus, right philosophy and principle should be established. It is not recommended to emphasize neither deterrence approach nor behavior modification approach. This should be also taken into consideration when setting up the principle and system of regulatory enforcement. In the process of Vienna Declaration, Europe and the U.S showed the fundamental differences in their approaches to safety regulation. Considering this, it is required to remain cautious at all times on what to be improved in the aspect of internal consistency within our system and also in the aspect of procedure.

The waste isolation pilot plant regulatory compliance program

International Nuclear Information System (INIS)

Mewhinney, J.A.; Kehrman, R.F.

1996-01-01

The passage of the WIPP Land Withdrawal Act of 1992 (LWA) marked a turning point for the Waste Isolation Pilot Plant (WIPP) program. It established a Congressional mandate to open the WIPP in as short a time as possible, thereby initiating the process of addressing this nation's transuranic (TRU) waste problem. The DOE responded to the LWA by shifting the priority at the WIPP from scientific investigations to regulatory compliance and the completion of prerequisites for the initiation of operations. Regulatory compliance activities have taken four main focuses: (1) preparing regulatory submittals; (2) aggressive schedules; (3) regulator interface; and (4) public interactions

Modeling Dynamic Regulatory Processes in Stroke

Science.gov (United States)

McDermott, Jason E.; Jarman, Kenneth; Taylor, Ronald; Lancaster, Mary; Shankaran, Harish; Vartanian, Keri B.; Stevens, Susan L.; Stenzel-Poore, Mary P.; Sanfilippo, Antonio

2012-01-01

The ability to examine the behavior of biological systems in silico has the potential to greatly accelerate the pace of discovery in diseases, such as stroke, where in vivo analysis is time intensive and costly. In this paper we describe an approach for in silico examination of responses of the blood transcriptome to neuroprotective agents and subsequent stroke through the development of dynamic models of the regulatory processes observed in the experimental gene expression data. First, we identified functional gene clusters from these data. Next, we derived ordinary differential equations (ODEs) from the data relating these functional clusters to each other in terms of their regulatory influence on one another. Dynamic models were developed by coupling these ODEs into a model that simulates the expression of regulated functional clusters. By changing the magnitude of gene expression in the initial input state it was possible to assess the behavior of the networks through time under varying conditions since the dynamic model only requires an initial starting state, and does not require measurement of regulatory influences at each time point in order to make accurate predictions. We discuss the implications of our models on neuroprotection in stroke, explore the limitations of the approach, and report that an optimized dynamic model can provide accurate predictions of overall system behavior under several different neuroprotective paradigms. PMID:23071432

Strengthening Regulatory Competence in a Changing Nuclear Regulatory Environment

International Nuclear Information System (INIS)

Illizastigui, P.F.

2016-01-01

The paper addresses the approach followed by the Cuban National Center for Nuclear Safety for the management of current and new competences of its regulatory staff with the aim of allowing those staff to effectively fulfill their core regulatory functions. The approach is realized through an Integrated System for Competence Building, which is based on the IAEA recommendations, shown to be effective in ensuring the necessary competence in the relevant areas. In the author’s opinion, competence of the regulatory staff in the area of human and organizational factors is of paramount importance and needs to be further strengthened in order to be able to assess safety performance at the facilities and detect early signs of deteriorating safety performance. The former is defined by the author as the core regulatory function “Analysis” which covers the entire spectrum of assessment tasks carried out by the regulatory staff to: a) detect declining safety performance, b) diagnose latent weaknesses (root causes) and c) make effective safety culture interventions. The author suggests that competence associated with the fulfillment of the analysis function is distinctly identified and dealt with separately in the current system of managing regulatory competence. (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.

Experience Transformed into Nuclear Regulatory Improvements in Russia

International Nuclear Information System (INIS)

Sapozhnikov, A.

2016-01-01

The third International Conference on Effective Nuclear Regulatory Systems (Canada, 2013) identified the main action items that should be addressed, implemented and followed up. The key technical and organizational areas important to strengthening reactor and spent fuel safety have been determined as following: • Regulatory lessons learned and actions taken (since the accident at the Fukushima Daiichi NPP); • Waste management and spent fuel safety; • Emergency management; • Emerging programmes; • Human and organizational factors, safety and security culture. Over time many activities based on results of the IAEA Integrated Regulatory Review Service in the Russian Federation, 2019, and post-mission, 2013, have been implemented. At present there is progress for the national action plan on nuclear safety, preparation and conducting of long term spent fuel management, complementary reviews for nuclear facilities other than Nuclear Power Plants, emergency exercises with the regulatory body participation, improving communication, development of national regulations and improvement of regulatory system in the whole. The regulatory body ensures assistance in development of national regulatory infrastructure, safety culture to the countries planning to construct Russian design facilities (NPPs, RRs). The report outlines the results and future actions to improve nuclear regulation based on systematic approach to safety and particularly reflects the specificity of taking measures for the research reactors. (author)

Developmental gene regulatory networks in sea urchins and what we can learn from them [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Megan L. Martik

2016-02-01

Full Text Available Sea urchin embryos begin zygotic transcription shortly after the egg is fertilized.  Throughout the cleavage stages a series of transcription factors are activated and, along with signaling through a number of pathways, at least 15 different cell types are specified by the beginning of gastrulation.  Experimentally, perturbation of contributing transcription factors, signals and receptors and their molecular consequences enabled the assembly of an extensive gene regulatory network model.  That effort, pioneered and led by Eric Davidson and his laboratory, with many additional insights provided by other laboratories, provided the sea urchin community with a valuable resource.  Here we describe the approaches used to enable the assembly of an advanced gene regulatory network model describing molecular diversification during early development.  We then provide examples to show how a relatively advanced authenticated network can be used as a tool for discovery of how diverse developmental mechanisms are controlled and work.

Hill functions for stochastic gene regulatory networks from master equations with split nodes and time-scale separation

Science.gov (United States)

Lipan, Ovidiu; Ferwerda, Cameron

2018-02-01

The deterministic Hill function depends only on the average values of molecule numbers. To account for the fluctuations in the molecule numbers, the argument of the Hill function needs to contain the means, the standard deviations, and the correlations. Here we present a method that allows for stochastic Hill functions to be constructed from the dynamical evolution of stochastic biocircuits with specific topologies. These stochastic Hill functions are presented in a closed analytical form so that they can be easily incorporated in models for large genetic regulatory networks. Using a repressive biocircuit as an example, we show by Monte Carlo simulations that the traditional deterministic Hill function inaccurately predicts time of repression by an order of two magnitudes. However, the stochastic Hill function was able to capture the fluctuations and thus accurately predicted the time of repression.

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

Science.gov (United States)

Ancans, Janis

2012-01-01

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

77 FR 40817 - Low-Level Radioactive Waste Regulatory Management Issues

Science.gov (United States)

2012-07-11

...-2011-0012] RIN-3150-AI92 Low-Level Radioactive Waste Regulatory Management Issues AGENCY: Nuclear... regulatory time of compliance for a low-level radioactive waste disposal facility, allowing licensees the... system, and revising the NRC's licensing requirements for land disposal of radioactive waste. DATES: The...

Analysis of regional timelines to set up a global phase III clinical trial in breast cancer: the adjuvant lapatinib and/or trastuzumab treatment optimization experience.

Science.gov (United States)

Metzger-Filho, Otto; de Azambuja, Evandro; Bradbury, Ian; Saini, Kamal S; Bines, José; Simon, Sergio D; Dooren, Veerle Van; Aktan, Gursel; Pritchard, Kathleen I; Wolff, Antonio C; Smith, Ian; Jackisch, Christian; Lang, Istvan; Untch, Michael; Boyle, Frances; Xu, Binghe; Baselga, Jose; Perez, Edith A; Piccart-Gebhart, Martine

2013-01-01

This study measured the time taken for setting up the different facets of adjuvant lapatinib and/or trastuzumab treatment optimization (ALTTO), an nternational phase III study being conducted in 44 participating countries. Time to regulatory authority (RA) approval, time to ethics committee/institutional review board (EC/IRB) approval, time from study approval by EC/IRB to first randomized patient, and time from first to last randomized patient were prospectively collected in the ALTTO study. Analyses were conducted by grouping countries into either geographic regions or economic classes as per the World Bank's criteria. South America had a significantly longer time to RA approval (median: 236 days, range: 21-257 days) than Europe (median: 52 days, range: 0-151 days), North America (median: 26 days, range: 22-30 days), and Asia-Pacific (median: 62 days, range: 37-75 days). Upper-middle economies had longer times to RA approval (median: 123 days, range: 21-257 days) than high-income (median: 47 days, range: 0-112 days) and lower-middle income economies (median: 57 days, range: 37-62 days). No significant difference was observed for time to EC/IRB approval across the studied regions (median: 59 days, range 0-174 days). Overall, the median time from EC/IRB approval to first recruited patient was 169 days (range: 26-412 days). This study highlights the long time intervals required to activate a global phase III trial. Collaborative research groups, pharmaceutical industry sponsors, and regulatory authorities should analyze the current system and enter into dialogue for optimizing local policies. This would enable faster access of patients to innovative therapies and enhance the efficiency of clinical research.

Risk undermined in the bilateral pharmaceutical regulatory system in Taiwan.

Science.gov (United States)

Wang, Hui-Po; Wang, Chun-Li

2018-04-01

The concept of Pharmacovigilance Planning and Risk Minimization Planning (PVP/RMP), initiated by the International Conference on Harmonization (ICH), addressed an important conceptual change from monitoring the safety of individual medicine to proactively conducting risk prevention for the minimization of medication error. However, the implementation of PVP/RMP is a challenge in societies like Taiwan where irrational medication and co-medication is prevalent. It is even more difficult in Taiwan where two regulatory bodies are governing pharmaceutical affairs, namely Taiwan Food and Drug Administration (TFDA) in charge of Western Medicine (WM) and the Department of Chinese Medicine and Pharmacy (DCMP) in charge of Traditional Chinese Medicine (TCM). There are thus dual-tract drug approval panels, two GMP controls and two independent adverse drug event reporting systems. This rendered irrational co-medication of WM and TCM undetectable and the standard tools for monitoring pharmacovigilance inapplicable. The bilateral regulatory system is conceptually unscientific in accordance with PVP/RMP and unethical from humanity point of view. The first part of this review delivers (1) social aspects of polypharmacy in Taiwan; (2) regulatory aspects of pharmaceutical administration; (3) risks undermined in the bilateral regulatory system and (4) pharmacoepidemiology in relation to the risk of polypharmacy. As evidence-based medicine (EBM) forms the fundamental risk-benefit assessment on medication, the second part of this review delivers (1) the scientific aspects of the beauty and the odds of biological system that governs host-xenobiotics interaction; (2) conceptual evolution from product management (pharmacovigilance) to risk management (PVP/RMP); (3) non-biased due process is essential for risk-benefit assessment on medicinal products and (4) the opinion of the authors on system building for safe medication. Copyright © 2018. Published by Elsevier B.V.

Regulatory networks, legal federalism, and multi-level regulatory systems

OpenAIRE

Kerber, Wolfgang; Wendel, Julia

2016-01-01

Transnational regulatory networks play important roles in multi-level regulatory regimes, as e.g, the European Union. In this paper we analyze the role of regulatory networks from the perspective of the economic theory of legal federalism. Often sophisticated intermediate institutional solutions between pure centralisation and pure decentralisation can help to solve complex tradeoff problems between the benefits and problems of centralised and decentralised solutions. Drawing upon the insight...

Review on the worldwide regulatory framework for biosimilars focusing on the Mexican case as an emerging market in Latin America.

Science.gov (United States)

Ibarra-Cabrera, Ricardo; Mena-Pérez, Sandra Carolina; Bondani-Guasti, Augusto; García-Arrazola, Roeb

2013-12-01

The global biopharmaceutical market is worth over $100 billion USD. Nearly 90% of these products will lose their patent in the next ten years, leading to the commercialization of their subsequent versions, known as 'biosimilars'. Biosimilars are much more complex molecules than chemically synthesized generics in terms of size, structure, stability, microheterogeneity, manufacture, etc. Therefore, a specific regulatory framework is needed in order to demonstrate their comparability with innovative products, as well as their quality, safety and efficacy. The EU published the first regulatory pathway in 2005 and has approved 14 biosimilars. Mexico has recently developed a clear regulatory pathway for these products. Their legal basis was established in Article 222 Bis of General Law of Health in 2009, clear specifications in the Regulation for Health Goods in 2011, and further requirements in the Mexican Official Norm NOM-EM-001-SSA1-2012. The aim of this review is to summarize the regulatory pathways for biosimilars in the world with a special focus on Mexican experience, so as contribute to the development of regulations in other countries. Copyright © 2013 Elsevier Inc. All rights reserved.

78 FR 33726 - Approval and Promulgation of Implementation Plans; Kentucky: Kentucky Portion of Cincinnati...

Science.gov (United States)

2013-06-05

... the Regional Office's normal hours of operation. The Regional Office's official hours of business are... model which was the latest approved emissions model at that time. That plan satisfied the CAA... plan included MVEBs that were derived with the MOVES model--the latest approved emissions model at that...

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

Science.gov (United States)

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

2017-06-01

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

Technical and regulatory challenges for digital instrumentation and control and control room systems in nuclear plants

International Nuclear Information System (INIS)

Torok, R.; Naser, J.; Harris, T.; Keithline, K.

2006-01-01

There are several unsettled technical and licensing issues in the areas of instrumentation and control (I and C), human factors, and updated control room designs that need coordinated, proactive industry attention. Some of these issues are already causing protracted regulatory reviews for existing plants, and left untreated, may cause substantial delays and increased costs for new plant combined construction and operating license approvals. Both industry and the NRC will have roles in resolving the key issues and addressing them in future design efforts and regulatory reviews. Where action is needed, the industry will want to minimize costs and risks by defining industry consensus solutions with corresponding technical bases. NEI has formed a working group to coordinate industry efforts and communications with NRC staff. The working group will also help determine priorities and coordinate both new and existing plant resources. EPRI will provide technical input and guidance for the working group. In order to be able to conduct reviews in a timely fashion, the NRC will likely need to enhance and expand staff resources as existing plants are upgraded and new plant reviews become more active. The industry initiative began with a workshop sponsored by EPRI and NEI on March 28-29, 2006, which led to the creation of the NEI working group. The working group has now identified and prioritized important generic issues, established resolution paths and schedules, and identified the roles of various stakeholders including utility companies, EPRI, NEI, vendors and the NRC. Through the course of this initiative I and C issues for both existing and new plants are being addressed. This paper describes the key I and C related technical and regulatory issues and their implications for new and operating plants, and provides a status report on the efforts to resolve them. (authors)

Marketing Approval of Ethical Kampo Medicines.

Science.gov (United States)

Hakamatsuka, Takashi

2017-01-01

Kampo medicine is an original traditional medicine in Japan. Currently, 148 ethical Kampo formulations (Kampo prescription drugs) are registered in the National Health Insurance Price List. Kampo medicines can be prescribed under the national insurance system, which shows that they are part of conventional medicine in Japan. Japan has a unified drug approval system that does not distinguish between Western and Kampo medicines, and both are subject to the same regulations. The application for the market approval of ethical Kampo medicines is based on the general notification for drugs, i.e., "Handling of Ethical Combination Drugs" in "Precautions Necessary When Applying for Drug Marketing Approval" (Yakushokushinsa Notification No. 1121-12 of November 21, 2014). Furthermore, applications for the market approval of ethical Kampo medicines should follow the Kampo-specific notification of "Handling of Ethical Kampo Medicines" (Yakushin Notification No. 804 of June 25, 1980). Data from comparative studies with standard decoctions must be submitted with approval applications according to Yakushin 2 Notification No. 120 of May 31, 1985. The safety, efficacy, and quality of Kampo medicines are comprehensively assured by the Japanese Pharmacopoeia, Good Manufacturing Practice, Good Agricultural and Collection Practices, marketing approval certificate, approval standard, and pharmacovigilance. I believe that the basic framework for the market approval of ethical Kampo medicines has been established as described above. The key factors for the practical application of superior manufacturing technology and research achievements and the promotion of drug development are the specific guidelines for the approval of drugs of herbal origin.

40 CFR 145.31 - Approval process.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Approval process. 145.31 Section 145.31 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE UIC PROGRAM REQUIREMENTS Program Approval, Revision and Withdrawal § 145.31 Approval process. (a...

40 CFR 52.2122 - Approval status.

Science.gov (United States)

2010-07-01

... sources covered by CTGs issued by the previous January. (b) EPA disapproved South Carolina's generic...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Carolina § 52.2122 Approval status. (a) With the exceptions set forth in this subpart, the Administrator approves South Carolina's plans for...

Directory of national competent authorities' approval certificates for package design, special form material and shipment of radioactive material. 1994 ed

International Nuclear Information System (INIS)

1994-08-01

This is the fifth annual report being published by the Secretariat of the International Atomic Energy Agency since implementing its database on package approval certificates (PACKTRAM) at the recommendation of the Standing Advisory Group on the Safe Transport of Radioactive Material (SAGSTRAM). The reporting format was established at consecutive meetings of SAGSTRAM, whose membership consists of national competent authorities responsible for the transport of radioactive material from those Member States who have a nuclear industry and others who have shown a keen interest in the IAEA's transport safety programme. Through the PACKTRAM database, the Secretariat collects administrative and technical information on package approval certificates to assist national competent authorities in regulating radioactive material movements in their country. The database carries information on extant certificates and those that expired within the last two complete calendar years. The 1985 Edition of IAEA Safety Series No. 6, the ''Regulations for the Safe Transport of Radioactive Material'' highlights the role of competent authorities in assuring regulatory compliance in their own countries. Package approval certificates are an important aspect of that function. This document aims to be a useful reference for competent authorities as well as for manufacturers and shippers of radioactive material

Directory of national competent authorities' approval certificates for package design, special form material and shipment of radioactive material. 1995 edition

International Nuclear Information System (INIS)

1995-09-01

This is the sixth annual report being published by the Secretariat of the International Atomic Energy Agency since implementing its database on package approval certificates (PACKTRAM) at the recommendation of the Standing Advisory Group on the Safe Transport of Radioactive Material (SAGSTRAM). The reporting format was established at consecutive meetings of SAGSTRAM, whose membership consists of national competent authorities responsible for the transport of radioactive material from those Member States who have a nuclear industry and others who have shown a keen interest in the IAEA's transport safety programme. Through the PACKTRAM database, the Secretariat collects administrative and technical information on package approval certificates to assist national competent authorities in regulating radioactive material movements in their country. The database carries information on extant certificates and those that expired within the last complete calendar year. The 1985 Edition of IAEA Safety Series No. 6, the ''Regulations for the Safe Transport of Radioactive Material'' highlights the role of competent authorities in assuring regulatory compliance in their own countries. Package approval certificates are an important aspect of that function. This document aims to be a useful reference for competent authorities as well as for manufacturers and shippers of radioactive material. 6 tabs

Safety culture as a matter of regulatory control and regulatory effectiveness

International Nuclear Information System (INIS)

Camargo, C.T.M.; Furieri, E.B.; Arrieta, L.A.I.; Almeida, C.U.C.

2002-01-01

More than 15 years have passed since the term 'safety culture' was introduced by the International Nuclear Safety Advisory Group (INSAG), and although the concept now is widely accepted, practical applications and characteristics have been disseminated mainly for nuclear power plant operating organizations. There is still a lack of international guidance on the use of safety culture as a regulatory matter and on the application of the concept within regulatory organizations. This work explores the meaning of safety culture in two different fields: as an element of safety management systems it shall be a matter of regulatory control; as a complementary tool for quality management it should be used to enhance regulatory effectiveness. Brazilian recent experience on regulating nuclear power reactors provide some examples on how the concept of safety culture may influence regulatory strategies and regulatory management. (author)

Regulatory requirements of the integrated technology demonstration program, Savannah River Site (U)

International Nuclear Information System (INIS)

Bergren, C.L.

1992-01-01

The integrated demonstration program at the Savannah River Site (SRS) involves demonstration, testing and evaluation of new characterization, monitoring, drilling and remediation technologies for soils and groundwater impacted by organic solvent contamination. The regulatory success of the demonstration program has developed as a result of open communications between the regulators and the technical teams involved. This open dialogue is an attempt to allow timely completion of applied environmental restoration demonstrations while meeting all applicable regulatory requirements. Simultaneous processing of multiple regulatory documents (satisfying RCRA, CERCLA, NEPA and various state regulations) has streamlined the overall permitting process. Public involvement is achieved as various regulatory documents are advertised for public comment consistent with the site's community relations plan. The SRS integrated demonstration has been permitted and endorsed by regulatory agencies, including the Environmental Protection Agency (EPA) and the South Carolina Department of Health and Environmental Control. EPA headquarters and regional offices are involved in DOE's integrated Demonstration Program. This relationship allows for rapid regulatory acceptance while reducing federal funding and time requirements. (author)

75 FR 48302 - Notice of Request for Extension of Approval of an Information Collection; Credit Account Approval...

Science.gov (United States)

2010-08-10

....gov ). FOR FURTHER INFORMATION CONTACT: For information on credit account approval for reimbursable..., at (301) 851-2908. SUPPLEMENTARY INFORMATION: Title: Credit Account Approval for Reimbursable... Inspection Service [Docket No. APHIS-2010-0071] Notice of Request for Extension of Approval of an Information...

78 FR 54617 - Notice of Request for Extension of Approval of an Information Collection; Credit Account Approval...

Science.gov (United States)

2013-09-05

...] Notice of Request for Extension of Approval of an Information Collection; Credit Account Approval for... (202) 799-7039 before coming. FOR FURTHER INFORMATION CONTACT: For information on credit account... Coordinator, at (301) 851-2908. SUPPLEMENTARY INFORMATION: Title: Credit Account Approval for Reimbursable...

EU-funded initiatives for real world evidence: descriptive analysis of their characteristics and relevance for regulatory decision-making.

Science.gov (United States)

Plueschke, Kelly; McGettigan, Patricia; Pacurariu, Alexandra; Kurz, Xavier; Cave, Alison

2018-06-14

A review of European Union (EU)-funded initiatives linked to 'Real World Evidence' (RWE) was performed to determine whether their outputs could be used for the generation of real-world data able to support the European Medicines Agency (EMA)'s regulatory decision-making on medicines. The initiatives were identified from publicly available websites. Their topics were categorised into five areas: 'Data source', 'Methodology', 'Governance model', 'Analytical model' and 'Infrastructure'. To assess their immediate relevance for medicines evaluation, their therapeutic areas were compared with the products recommended for EU approval in 2016 and those included in the EMA pharmaceutical business pipeline. Of 171 originally identified EU-funded initiatives, 65 were selected based on their primary and secondary objectives (35 'Data source' initiatives, 15 'Methodology', 10 'Governance model', 17 'Analytical model' and 25 'Infrastructure'). These 65 initiatives received over 734 million Euros of public funding. At the time of evaluation, the published outputs of the 40 completed initiatives did not always match their original objectives. Overall, public information was limited, data access was not explicit and their sustainability was unclear. The topics matched 8 of 14 therapeutic areas of the products recommended for approval in 2016 and 8 of 15 therapeutic areas in the 2017-2019 pharmaceutical business pipeline. Haematology, gastroenterology or cardiovascular systems were poorly represented. This landscape of EU-funded initiatives linked to RWE which started before 31 December 2016 highlighted that the immediate utilisation of their outputs to support regulatory decision-making is limited, often due to insufficient available information and to discrepancies between outputs and objectives. Furthermore, the restricted sustainability of the initiatives impacts on their downstream utility. Multiple projects focussing on the same therapeutic areas increase the likelihood of

78 FR 68454 - Agency Information Collection Activities; Proposed Collection; Comment Request; Patent Term...

Science.gov (United States)

2013-11-14

... review period revision. Where a patented product must receive FDA approval before marketing is permitted.... Petitioners may request reductions in the regulatory review time if FDA marketing approval was not pursued..., including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility...

75 FR 61493 - Agency Information Collection Activities; Proposed Collection; Comment Request; Patent Term...

Science.gov (United States)

2010-10-05

... review period revision. Where a patented product must receive FDA approval before marketing is permitted.... Petitioners may request reductions in the regulatory review time if FDA marketing approval was not pursued... information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality...

A unified architecture of transcriptional regulatory elements

DEFF Research Database (Denmark)

Andersson, Robin; Sandelin, Albin Gustav; Danko, Charles G.

2015-01-01

Gene expression is precisely controlled in time and space through the integration of signals that act at gene promoters and gene-distal enhancers. Classically, promoters and enhancers are considered separate classes of regulatory elements, often distinguished by histone modifications. However...... and enhancers are considered a single class of functional element, with a unified architecture for transcription initiation. The context of interacting regulatory elements and the surrounding sequences determine local transcriptional output as well as the enhancer and promoter activities of individual elements....

40 CFR 52.1772 - Approval status.

Science.gov (United States)

2010-07-01

...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) North Carolina § 52.1772 Approval status. (a) With the exceptions set forth in this subpart, the Administrator approves North Carolina's plans for... CTGs issued by the previous January. (b) New Source review permits issued pursuant to section 173 of...