WorldWideScience

Sample records for regulatory approval times

  1. Analysis of time to regulatory and ethical approval of SATVI TB ...

    African Journals Online (AJOL)

    Background. Tuberculosis (TB) vaccine trials in South Africa must be approved by the Medicines Control Council (MCC) and by a human research ethics committee (HREC). Delays in regulatory and ethical approval may affect operational and budget planning and clinical development of the product. Aim. Our aim was to ...

  2. 75 FR 59771 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the...

    Science.gov (United States)

    2010-09-28

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the Proposed Rule.... I. Introduction On July 27, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k... pertinent distribution-related information from its members in a timely fashion to facilitate its Regulation...

  3. 7 CFR 1710.105 - State regulatory approvals.

    Science.gov (United States)

    2010-01-01

    ... and Basic Policies § 1710.105 State regulatory approvals. (a) In States where a borrower is required... loans are approved by RUS: (1) Loans requiring an Environmental Impact Statement; (2) Loans to finance...

  4. 76 FR 66344 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-10-26

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... 31, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of... consolidation process, see Information Notice, March 12, 2008 (Rulebook Consolidation Process). For convenience...

  5. 75 FR 17456 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-04-06

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... terms. For more information about the rulebook consolidation process, see Information Notice, March 12...

  6. 75 FR 41254 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2010-07-15

    ... registered capacity, may work in other investment-related industries, such as financial planning, or may seek...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a Proposed Rule..., 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and...

  7. 75 FR 5157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-02-01

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... Consolidated FINRA Rulebook January 25, 2010. On December 2, 2009, the Financial Industry Regulatory Authority... later in the rulebook consolidation process. It is therefore ordered, pursuant to Section 19(b)(2) of...

  8. 75 FR 43588 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2010-07-26

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a Proposed Rule... FINRA Rule 4320 in the Consolidated FINRA Rulebook July 20, 2010. On May 21, 2010, the Financial... application by their terms. For more information about the rulebook consolidation process, see Information...

  9. 30 CFR 906.10 - State regulatory program approval.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false State regulatory program approval. 906.10 Section 906.10 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE COLORADO § 906.10 State...

  10. 77 FR 74722 - Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Order Approving Proposed Rule...

    Science.gov (United States)

    2012-12-17

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68401; File No. SR-CME-2012-42] Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Order Approving Proposed Rule Change Regarding the Valuation of... to approve a proposed rule change of a self-regulatory organization if it finds that such proposed...

  11. 78 FR 69168 - Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed...

    Science.gov (United States)

    2013-11-18

    ... approve a proposed rule change of a self-regulatory organization if it finds that such proposed rule... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70848; File No. SR-NSCC-2013-10] Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed Rule Change To...

  12. 77 FR 40394 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Science.gov (United States)

    2012-07-09

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67333; File No. SR-OCC-2012-07] Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule Change Relating to Adjustment... to approve a proposed rule change of a self-regulatory organization if it finds that such proposed...

  13. 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...

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

    Science.gov (United States)

    Nakayama, Hiroki; Tsukamoto, Katsura

    2018-04-17

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

  15. Regulatory approvals in a large multinational clinical trial: the ESPRIT experience.

    Science.gov (United States)

    McNay, Laura A; Tavel, Jorge A; Oseekey, Karen; McDermott, Cathy M; Mollerup, David; Bebchuk, Judith D

    2002-02-01

    While accepted as serving an important function to safeguard human subjects, the process of obtaining regulatory approvals to conduct clinical trials is generally regarded as cumbersome and time-consuming. For large multinational trials, U.S. federally sponsored human subject research abroad involves specific U.S. regulatory requirements, in addition to those of the host country, that act as further hurdles. These requirements may include obtaining an Assurance of Protection for Human Subjects from the Office of Human Research Protection of the U.S. Department of Health and Human Services, maintaining specific Ethics Committee/Institutional Review Board (EC/IRB) composition, and incorporating mandated elements in informed consents, all of which may differ from local policies and guidelines. Specific examples of issues that led to delays in regulatory approvals for sites participating in the multinational clinical trial entitled Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) are presented here. While the goal of these requirements is to protect the rights and welfare of human subjects, they may create substantial delays and engender resentment over the notion of lack of respect for individual country sovereignty. Substudies within ESPRIT have been undertaken to obtain feedback from EC/IRB chairpersons, site personnel responsible for processing the required assurances, ESPRIT investigators, and study participants regarding aspects of current U.S. regulatory requirements related to human subject protection and ethical issues in multinational research. The purpose of these substudies is to compare the attitudes and experiences across countries regarding important ethical issues associated with conducting ESPRIT. One objective of the substudies is to gather additional insight to the impact of U.S. regulatory processes. Another is to help to inform the debate about how to best maximize the rights and welfare of clinical trial

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

    Science.gov (United States)

    Rhodes, Linda

    2018-05-01

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

  17. 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...

  18. Evaluation of regulatory processes affecting nuclear power plant early site approval and standardization

    International Nuclear Information System (INIS)

    1983-12-01

    This report presents the results of a survey and evaluation of existing federal, state and local regulatory considerations affecting siting approval of power plants in the United States. Those factors that may impede early site approval of nuclear power plants are identified, and findings related to the removal of these impediments and the general improvement of the approval process are presented. A brief evaluation of standardization of nuclear plant design is also presented

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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.

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 30 CFR 906.15 - Approval of Colorado regulatory program amendments.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Approval of Colorado regulatory program amendments. 906.15 Section 906.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE COLORADO...

  14. IRT‑Sofia, HEU to LEU conversion: regulatory approval tasks solution overview

    International Nuclear Information System (INIS)

    Mitev, Mladen; Belousov, Sergey; Dimitrov, Dobromir

    2014-01-01

    The HEU to LEU conversion of the IRT–Sofia research reactor of the Institute for Nuclear Research and Nuclear Energy of the Bulgarian Academy of Sciences was jointly studied with the Argonne National Laboratory as a part of the RERTR Programme. The main purpose of the collaboration consisted in accomplishment of safety analyses and preparation of documents used for regulatory approval tasks solution. The main steps and results which are fundamental for the preparation of IRT–Sofia Safety Analyses Report including Operating Limits and Conditions are presented in this paper. The documents prepared by INRNE in accordance with the European nuclear safety requirements and IAEA recommendations were submitted for approval to the Bulgarian Nuclear Regulatory Agency at the end of 2010. Key words: research reactor, safety analyses report, Nuclear Regulatory Agency

  15. 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...

  16. 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.

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

    International Nuclear Information System (INIS)

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

    1993-12-01

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

  18. A Tool for Predicting Regulatory Approval After Phase II Testing of New Oncology Compounds.

    Science.gov (United States)

    DiMasi, J A; Hermann, J C; Twyman, K; Kondru, R K; Stergiopoulos, S; Getz, K A; Rackoff, W

    2015-11-01

    We developed an algorithm (ANDI) for predicting regulatory marketing approval for new cancer drugs after phase II testing has been conducted, with the objective of providing a tool to improve drug portfolio decision-making. We examined 98 oncology drugs from the top 50 pharmaceutical companies (2006 sales) that first entered clinical development from 1999 to 2007, had been taken to at least phase II development, and had a known final outcome (research abandonment or regulatory marketing approval). Data on safety, efficacy, operational, market, and company characteristics were obtained from public sources. Logistic regression and machine-learning methods were used to provide an unbiased approach to assess overall predictability and to identify the most important individual predictors. We found that a simple four-factor model (activity, number of patients in the pivotal phase II trial, phase II duration, and a prevalence-related measure) had high sensitivity and specificity for predicting regulatory marketing approval. © 2015 American Society for Clinical Pharmacology and Therapeutics.

  19. 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.)

  20. 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...

  1. 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...

  2. 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...

  3. 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)

  4. 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.

  5. 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...

  6. 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.

  7. 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...

  8. 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...

  9. 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...

  10. 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,...

  11. 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.

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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...

  2. 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

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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...

  7. 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.

  8. 78 FR 8640 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change To...

    Science.gov (United States)

    2013-02-06

    ... provides recipients with uncompressed real-time data regarding the current status of price and size... (``NBO''), or the Final Last Sale Eligible Trade,\\10\\ depending on market conditions at the time of the... and Reference Sell Shares to potentially manipulate the price of the auction.\\20\\ By disseminating...

  9. 78 FR 21657 - Self-Regulatory Organizations; International Securities Exchange LLC; Order Approving, on an...

    Science.gov (United States)

    2013-04-11

    ... market during Limit States and Straddle States. Given the Exchange's recognition of the potential for... affected, each dataset will include, among other information: stock symbol, option symbol, time at the...

  10. 78 FR 40239 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Granting Approval to Proposed Rule...

    Science.gov (United States)

    2013-07-03

    ... Vacancies A Member Representative Director is defined in relevant part in Article I of the Current By-Laws... board.\\18\\ The Exchange has stated that, under these circumstances, time is of the essence and waiting...

  11. 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.

  12. 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...

  13. 77 FR 26061 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

    Science.gov (United States)

    2012-05-02

    ... SHORT subscription service, which is currently only available on a current basis through the real-time... partially offset costs associated with operating the SHORT System and producing and disseminating... the MSRB's Short-Term Obligation Rate Transparency System April 26, 2012. I. Introduction On February...

  14. 77 FR 17557 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

    Science.gov (United States)

    2012-03-26

    ... based on a transaction in a security for which each bond costs less than $1,000.\\9\\ \\9\\ For example, if... the Real-Time Transaction Reporting System March 20, 2012. I. Introduction On January 20, 2012, the... Transaction Reporting System. The proposed rule change was published for comment in the Federal Register on...

  15. 75 FR 72850 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

    Science.gov (United States)

    2010-11-26

    ... costs associated with operating RTRS and producing and disseminating transaction reports to subscribers... Change Consisting of Fee Changes to Its Real-Time Transaction Price Service and Comprehensive Transaction Price Service, and Termination of its T+1 Transaction Price Service November 18, 2010. I. Introduction...

  16. 76 FR 37162 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Science.gov (United States)

    2011-06-24

    ... of OCC's Internal Cross-Margining Program To Include the Ability of a Pair of Affiliated Clearing... change is to expand OCC's internal cross- margining program to permit a pair of affiliated clearing... program for affiliated clearing members until after such time that the CFTC has issued an order or amended...

  17. 76 FR 35491 - Self-Regulatory Organizations; Chicago Board Options Exchange, Inc.; Order Granting Approval of...

    Science.gov (United States)

    2011-06-17

    ... the Exchange's electronic book at the same price. Specifically, the QCC Order type would permit TPHs... of shares of the same issuer, or involve the securities of participants in mergers or with intentions... the book at the price as a QCC order at the time of execution.\\14\\ The commenter argued that in an...

  18. 75 FR 61533 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Granting Approval of...

    Science.gov (United States)

    2010-10-05

    ... highly liquid and capitalized German stocks ranked by float-adjusted market capitalization.\\4\\ The management board of Deutsche B[ouml]rse AG (``DBAG'') decides whether changes are to be made to the... p.m. and 1:05 p.m. (German time) on the third Friday of the expiration month, which generally...

  19. 77 FR 75466 - Self-Regulatory Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change...

    Science.gov (United States)

    2012-12-20

    ....\\8\\ This includes the potential use of the clearing fund as a source of liquidity should it ever be... reduce the risk that the assets in the clearing fund might at any time be insufficient to enable OCC to... Determining the Minimum Clearing Fund Size To Include Consideration of the Amount Necessary To Draw on Secured...

  20. 78 FR 22357 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Order Approving, on...

    Science.gov (United States)

    2013-04-15

    ... have been resting on the Book; or (2) Immediately prior to the time the Market Maker enters a new quote... reaches the upper price band, the market for an individual security enters a 15-second Limit State, and..., allowing options market makers the flexibility to choose whether to enter quotes, and to do so without...

  1. 75 FR 82112 - Self-Regulatory Organizations; National Securities Clearing Corporation; Order Granting Approval...

    Science.gov (United States)

    2010-12-29

    ...\\ Notice of the proposal was published in the Federal Register on October 25, 2010.\\2\\ The Commission... exceptions (e.g., ``don't know'' or ``DK'' obligations) in an efficient and timely manner. The OW will also...(a). RECAPS provides reject and DK capabilities for received advisories. Advisories that are either...

  2. 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...

  3. 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...

  4. 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...

  5. 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

  6. 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...

  7. 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

  8. 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).

  9. 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...

  10. 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...

  11. 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

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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.

  17. 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...

  18. 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...

  19. 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...

  20. 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

  1. 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...

  2. 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

  3. 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.

  4. 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.

  5. 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,

  6. 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.

  7. 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'

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 76 FR 10073 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change...

    Science.gov (United States)

    2011-02-23

    ..., primarily China, Hong Kong, India, Indonesia, South Korea, Malaysia, the Philippines, Singapore, Taiwan, and... par value traded to be considered as an eligible investment. Economic and other conditions in Asia may... will change from time to time in response to economic events and changes to the credit ratings of the...

  15. 76 FR 67783 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change To Amend...

    Science.gov (United States)

    2011-11-02

    ... benefits to the Corporation of their significant ownership for a certain period of time, through their... its related persons, from having or exercising more than 20% of the voting power of the capital stock...

  16. 78 FR 22001 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Accelerated Approval of a...

    Science.gov (United States)

    2013-04-12

    ... recognition of the potential for unreliable NBBOs in the options markets during Limit States and Straddle... include, among other information: Stock symbol, option symbol, time at the start of the Limit State or...

  17. 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.

  18. 75 FR 82420 - Self-Regulatory Organizations, The NASDAQ Stock Market LLC; Order Approving Proposed Rule Change...

    Science.gov (United States)

    2010-12-30

    ...). SPACs are companies that raise capital in an initial public offering (``IPO'') to enter into future undetermined business combinations through mergers, capital stock exchanges, asset acquisitions, stock... issue additional shares at the time of the business combination to raise capital.\\17\\ According to the...

  19. 76 FR 199 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change...

    Science.gov (United States)

    2011-01-03

    ... p.m. Eastern Time and at the close of trading on each Business Day \\12\\ by Bloomberg L.P. and... information services such as Bloomberg or Reuters. The specific contract specifications for the component... and market news free of charge on its Web site. In addition, the Funds will provide Web site...

  20. 78 FR 785 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change...

    Science.gov (United States)

    2013-01-04

    ... sources, or on- line information services such as Bloomberg or Reuters. Complete real- time data for the Futures Contracts is available by subscription from Reuters and Bloomberg. The relevant Futures Exchanges also provide delayed futures information on current and past trading sessions and market news free of...

  1. 76 FR 58549 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Approving a Proposed Rule Change To List...

    Science.gov (United States)

    2011-09-21

    ... vendors worldwide, including Bloomberg and Reuters. In addition, the Exchange further represents that complete real-time data for such contracts is available by subscription from Reuters and Bloomberg. CBOT... market news free of charge on their websites. The specific contract specifications for such contracts are...

  2. 76 FR 38714 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Order Approving a Proposed Rule Change To...

    Science.gov (United States)

    2011-07-01

    ... inconsistent with just and equitable principles of trade to engage in a pattern or practice of using Non... handling procedures because such orders are priced at the very inside of the market but are temporarily un... available liquidity for incoming orders and provide price improvement for market participants at times when...

  3. 76 FR 38712 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving a Proposed Rule Change To...

    Science.gov (United States)

    2011-07-01

    ... to BATS Rule 11.13 to state that the Exchange will consider it inconsistent with just and equitable... the very inside of the market but are temporarily un-executable at their full limit price due to the... price improvement for market participants at times when such participants are not receiving executions...

  4. 77 FR 22022 - Self-Regulatory Organizations; C2 Options Exchange, Incorporated; Order Approving a Proposed Rule...

    Science.gov (United States)

    2012-04-12

    ...-rata, and price-time with primary public customer and secondary trade participation right priority and...'') is within designated size and price parameters, as determined by C2 for the individual leg. See C2... within certain parameters determined by C2 and for which the NBBO is within designated size and price...

  5. 78 FR 25774 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

    Science.gov (United States)

    2013-05-02

    ... potential for price manipulation of the Shares. \\30\\ See id. at 16017. In support of this proposal, the... price and trading volume of the Shares will be continually available on a real- time basis throughout... Shares and any underlying exchange-traded product.\\24\\ Intra-day, executable price quotations of the...

  6. 77 FR 61453 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change...

    Science.gov (United States)

    2012-10-09

    ... market country. Foreign debt securities include direct investments in non-U.S. dollar-denominated debt... for economic growth and increased capital market participation by foreign investors. The Investment... sufficiently liquid at the time of investment.\\13\\ Foreign government obligations may include debt obligations...

  7. 75 FR 6072 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving Proposed Rule Change...

    Science.gov (United States)

    2010-02-05

    ... delisting process if such rule changes are found to benefit Nasdaq's financial position.\\46\\ [[Page 6075... SEC filing made by listing companies, including proxies and annual and quarterly financial reports... the changes that have taken place in the financial markets, the existing time periods are unreasonably...

  8. 78 FR 25512 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

    Science.gov (United States)

    2013-05-01

    ... Market Makers. Under the proposed rules, quotations and quotation sizes may be entered into PSX only by a... terminated by the Exchange if the PSX Market Maker fails to enter quotations in the issue within five (5... in PSX's quotation montage at all times. Proposed Rule 3213(a)(2) would require a PSX Market Maker...

  9. 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

  10. 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

  11. 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…

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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)

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Inference of time-delayed gene regulatory networks based on dynamic Bayesian network hybrid learning method.

    Science.gov (United States)

    Yu, Bin; Xu, Jia-Meng; Li, Shan; Chen, Cheng; Chen, Rui-Xin; Wang, Lei; Zhang, Yan; Wang, Ming-Hui

    2017-10-06

    Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model. DBNCS algorithm first uses CMI2NI (conditional mutual inclusive information-based network inference) algorithm for network structure profiles learning, namely the construction of search space. Then the redundant regulations are removed by using the recursive optimization algorithm (RO), thereby reduce the false positive rate. Secondly, the network structure profiles are decomposed into a set of cliques without loss, which can significantly reduce the computational complexity. Finally, DBN model is used to identify the direction of gene regulation within the cliques and search for the optimal network structure. The performance of DBNCS algorithm is evaluated by the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in Escherichia coli , and compared with other state-of-the-art methods. The experimental results show the rationality of the algorithm design and the outstanding performance of the GRNs.

  2. 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.

  3. 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

  4. 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.

  5. Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia.

    Science.gov (United States)

    Weiss, Lukas; Melchardt, Thomas; Egle, Alexander; Grabmer, Christoph; Greil, Richard; Tinhofer, Inge

    2011-05-15

    Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression. T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data. The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028). Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia. 2010 American Cancer Society.

  6. 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...

  7. 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...

  8. 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.

  9. Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation

    Directory of Open Access Journals (Sweden)

    Mary Prahl

    2016-10-01

    Full Text Available Abstract Background In malaria-endemic areas, the first exposure to malaria antigens often occurs in utero when the fetal immune system is poised towards the development of tolerance. Children exposed to placental malaria have an increased risk of clinical malaria in the first few years of life compared to unexposed children. Recent work has suggested the potential of pregnancy-associated malaria to induce immune tolerance in children living in malaria-endemic areas. A study was completed to evaluate the effect of malaria exposure during pregnancy on fetal immune tolerance and effector responses. Methods Using cord blood samples from a cohort of mother-infant pairs followed from early in pregnancy until delivery, flow cytometry analysis was completed to assess the relationship between pregnancy-associated malaria and fetal cord blood CD4 and dendritic cell phenotypes. Results Cord blood FoxP3+ Treg counts were higher in infants born to mothers with Plasmodium parasitaemia early in pregnancy (12–20 weeks of gestation; p = 0.048, but there was no association between Treg counts and the presence of parasites in the placenta at the time of delivery (by loop-mediated isothermal amplification (LAMP; p = 0.810. In contrast, higher frequencies of activated CD4 T cells (CD25+FoxP3−CD127+ were observed in the cord blood of neonates with active placental Plasmodium infection at the time of delivery (p = 0.035. This population exhibited evidence of effector memory differentiation, suggesting priming of effector T cells in utero. Lastly, myeloid dendritic cells were higher in the cord blood of infants with histopathologic evidence of placental malaria (p < 0.0001. Conclusion Together, these data indicate that in utero exposure to malaria drives expansion of both regulatory and effector T cells in the fetus, and that the timing of this exposure has a pivotal role in determining the polarization of the fetal immune response.

  10. Inference of gene regulatory networks from time series by Tsallis entropy

    Directory of Open Access Journals (Sweden)

    de Oliveira Evaldo A

    2011-05-01

    Full Text Available Abstract Background The inference of gene regulatory networks (GRNs from large-scale expression profiles is one of the most challenging problems of Systems Biology nowadays. Many techniques and models have been proposed for this task. However, it is not generally possible to recover the original topology with great accuracy, mainly due to the short time series data in face of the high complexity of the networks and the intrinsic noise of the expression measurements. In order to improve the accuracy of GRNs inference methods based on entropy (mutual information, a new criterion function is here proposed. Results In this paper we introduce the use of generalized entropy proposed by Tsallis, for the inference of GRNs from time series expression profiles. The inference process is based on a feature selection approach and the conditional entropy is applied as criterion function. In order to assess the proposed methodology, the algorithm is applied to recover the network topology from temporal expressions generated by an artificial gene network (AGN model as well as from the DREAM challenge. The adopted AGN is based on theoretical models of complex networks and its gene transference function is obtained from random drawing on the set of possible Boolean functions, thus creating its dynamics. On the other hand, DREAM time series data presents variation of network size and its topologies are based on real networks. The dynamics are generated by continuous differential equations with noise and perturbation. By adopting both data sources, it is possible to estimate the average quality of the inference with respect to different network topologies, transfer functions and network sizes. Conclusions A remarkable improvement of accuracy was observed in the experimental results by reducing the number of false connections in the inferred topology by the non-Shannon entropy. The obtained best free parameter of the Tsallis entropy was on average in the range 2.5

  11. 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.

  12. 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

  13. 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)

  14. On the psychology of time in action: regulatory mode orientations and procrastination.

    Science.gov (United States)

    Pierro, Antonio; Giacomantonio, Mauro; Pica, Gennaro; Kruglanski, Arie W; Higgins, E Tory

    2011-12-01

    Six studies explored the relations of the regulatory modes of locomotion and assessment to individuals' tendency toward procrastination. Across academic and organizational contexts, and a variety of ways of assessing procrastination, the authors found assessment to be positively related to procrastination and locomotion to be negatively related to procrastination. Discussion considered implications of these findings to task environments that may instill the tendencies toward locomotion or assessment and to task requirements where timeliness and punctuality are (or are not) prioritized.

  15. 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?’

  16. 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.

  17. 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)

  18. Evolution of Transcriptional Regulatory Networks in Pseudomonas aeruginosa During Long Time Growth in Human Hosts

    DEFF Research Database (Denmark)

    Andresen, Eva Kammer

    extent these observations relate to natural microbial populations. The focus of this thesis has been to study how regulatory networks evolve in natural systems. By using a particular infectious disease scenario (human associated persistent airway infections caused by the bacterium Pseudomonas aeruginosa...... in global regulator genes facilitate the generation of novel phenotypes which again facilitate the shift in life-style of the bacterium from an environmental opportunistic pathogen to a human airway specific pathogen. These findings are not only applicable to P. aeruginosa specific studies, but suggest that...

  19. 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.

  20. 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.

  1. 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.

  2. Timing Embryo Segmentation: Dynamics and Regulatory Mechanisms of the Vertebrate Segmentation Clock

    Science.gov (United States)

    Resende, Tatiana P.; Andrade, Raquel P.; Palmeirim, Isabel

    2014-01-01

    All vertebrate species present a segmented body, easily observed in the vertebrate column and its associated components, which provides a high degree of motility to the adult body and efficient protection of the internal organs. The sequential formation of the segmented precursors of the vertebral column during embryonic development, the somites, is governed by an oscillating genetic network, the somitogenesis molecular clock. Herein, we provide an overview of the molecular clock operating during somite formation and its underlying molecular regulatory mechanisms. Human congenital vertebral malformations have been associated with perturbations in these oscillatory mechanisms. Thus, a better comprehension of the molecular mechanisms regulating somite formation is required in order to fully understand the origin of human skeletal malformations. PMID:24895605

  3. Regulatory T cells in acute myelogenous leukemia: is it time for immunomodulation?

    Science.gov (United States)

    Ustun, Celalettin; Miller, Jeffrey S; Munn, David H; Weisdorf, Daniel J; Blazar, Bruce R

    2011-11-10

    The microenviroment of acute myelogenous leukemia (AML) is suppressive for immune effector cells. Regulatory T cells (Tregs) have been recognized as a contributor factor and may be recruited and exploited by leukemic cells to evade immunesurveillance. Studies have shown that the frequencies of marrow and blood Tregs are greater in patients with AML than in control patients. Although increased Tregs have been associated with a decreased risk of GVHD after allogeneic HCT and hence may impede the graft-versus-tumor effect, recent findings indicate that that this may not be the case. Because there is a need to improve outcomes of standard treatment (chemotherapy with or without allogeneic HCT) in AML, targeting Tregs present an outstanding opportunity in AML because discoveries may apply throughout its treatment. Here, we review data on the roles of Tregs in mediating immune system-AML interactions. We focused on in vitro, animal, and observational human studies of Tregs in AML biology, development, prognosis, and therapy in different settings (eg, vaccination and HCT). Manipulation of Tregs or other types of immunomodulation may become a part of AML treatment in the future.

  4. 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.

  5. 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.

  6. 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...

  7. 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

  8. 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.

  9. Hopf Bifurcation Analysis of a Gene Regulatory Network Mediated by Small Noncoding RNA with Time Delays and Diffusion

    Science.gov (United States)

    Li, Chengxian; Liu, Haihong; Zhang, Tonghua; Yan, Fang

    2017-12-01

    In this paper, a gene regulatory network mediated by small noncoding RNA involving two time delays and diffusion under the Neumann boundary conditions is studied. Choosing the sum of delays as the bifurcation parameter, the stability of the positive equilibrium and the existence of spatially homogeneous and spatially inhomogeneous periodic solutions are investigated by analyzing the corresponding characteristic equation. It is shown that the sum of delays can induce Hopf bifurcation and the diffusion incorporated into the system can effect the amplitude of periodic solutions. Furthermore, the spatially homogeneous periodic solution always exists and the spatially inhomogeneous periodic solution will arise when the diffusion coefficients of protein and mRNA are suitably small. Particularly, the small RNA diffusion coefficient is more robust and its effect on model is much less than protein and mRNA. Finally, the explicit formulae for determining the direction of Hopf bifurcation and the stability of the bifurcating periodic solutions are derived by employing the normal form theory and center manifold theorem for partial functional differential equations. Finally, numerical simulations are carried out to illustrate our theoretical analysis.

  10. Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3

    KAUST Repository

    Schmidt, Angelika; Marabita, Francesco; Kiani, Narsis A.; Gross, Catharina C.; Johansson, Henrik J.; É liá s, Szabolcs; Rautio, Sini; Eriksson, Matilda; Fernandes, Sunjay Jude; Silberberg, Gilad; Ullah, Ubaid; Bhatia, Urvashi; Lä hdesmä ki, Harri; Lehtiö , Janne; Gomez-Cabrero, David; Wiendl, Heinz; Lahesmaa, Riitta; Tegner, Jesper

    2018-01-01

    BackgroundRegulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest

  11. 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

  12. Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3

    KAUST Repository

    Schmidt, Angelika

    2018-04-27

    BackgroundRegulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood.ResultsTo gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by a targeted shRNA screen confirming a functional role in FOXP3 induction, discriminant analyses classifying iTregs accordingly, and comparable expression in an independent novel iTreg RNA-Seq dataset.ConclusionThe data generated by this novel approach facilitates understanding of the molecular mechanisms underlying iTreg generation as well as of the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune, and inflammatory diseases.

  13. 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...

  14. 21 CFR 316.23 - Timing of requests for orphan-drug designation; designation of already approved drugs.

    Science.gov (United States)

    2010-04-01

    ...) A sponsor may request orphan-drug designation at any time in the drug development process prior to... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Timing of requests for orphan-drug designation..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan...

  15. 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.

  16. Just-in-time control of Spo0A synthesis in Bacillus subtilis by multiple regulatory mechanisms.

    Science.gov (United States)

    Chastanet, Arnaud; Losick, Richard

    2011-11-01

    The response regulator Spo0A governs multiple developmental processes in Bacillus subtilis, including most conspicuously sporulation. Spo0A is activated by phosphorylation via a multicomponent phosphorelay. Previous work has shown that the Spo0A protein is not rate limiting for sporulation. Rather, Spo0A is present at high levels in growing cells, rapidly rising to yet higher levels under sporulation-inducing conditions, suggesting that synthesis of the response regulator is subject to a just-in-time control mechanism. Transcription of spo0A is governed by a promoter switching mechanism, involving a vegetative, σ(A)-recognized promoter, P(v), and a sporulation σ(H)-recognized promoter, P(s), that is under phosphorylated Spo0A (Spo0A∼P) control. The spo0A regulatory region also contains four (including one identified in the present work) conserved elements that conform to the consensus binding site for Spo0A∼P binding sites. These are herein designated O(1), O(2), O(3), and O(4) in reverse order of their proximity to the coding sequence. Here we report that O(1) is responsible for repressing P(v) during the transition to stationary phase, that O(2) is responsible for repressing P(s) during growth, that O(3) is responsible for activating P(s) at the start of sporulation, and that O(4) is dispensable for promoter switching. We also report that Spo0A synthesis is subject to a posttranscriptional control mechanism such that translation of mRNAs originating from P(v) is impeded due to RNA secondary structure whereas mRNAs originating from P(s) are fully competent for protein synthesis. We propose that the opposing actions of O(2) and O(3) and the enhanced translatability of mRNAs originating from P(s) create a highly sensitive, self-reinforcing switch that is responsible for producing a burst of Spo0A synthesis at the start of sporulation.

  17. 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.

  18. Time-Line in HFEA Developments and Regulatory Challenges: 20 Years of Overseeing Fertility Practices and Research in the UK.

    Science.gov (United States)

    Agrawal, Rina; Burt, Elizabeth; Homburg, Roy

    2013-12-01

    In the wake of political upheaval, the Human Fertilisation and Embryo Authority (HFEA) has faced increasing insecurity over its future as a pivotal regulatory body of fertility practices in the UK. HFEA regulates activities by means of licensing, audit, and inspection of fertility centers and maintaining the Code of Practice, which ensures the optimum undertaking of licensed activities by fertility centers. In 2009, amendments to the 1990 Act came into force representing an amalgamation of cumulative proposals, debates, and changes in legislation, which have shaped the world of reproductive medicine. The medical world has, in many cases, adapted to righteous political and social demands, and continues to evolve at a rapid rate. The HFEA has faced many regulatory challenges and changes, and through this study, we aim to provide an overview of some of these changes, particularly those during the last 10 years and the implications that they may have had to fertility practices.

  19. 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…

  20. 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,...

  1. 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.)

  2. 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

  3. 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....

  4. Relations between chronic regulatory focus and future time perspective: Results of a cross-lagged structural equation model

    NARCIS (Netherlands)

    Zacher, H.; Lange, A.H. de

    2011-01-01

    Future time perspective - the way individuals perceive their remaining time in life - importantly influences socio-emotional goals and motivational outcomes. Recently, researchers have called for studies that investigate relationships between personality and future time perspective. Using a

  5. Relations between chronic regulatory focus and future time perspective : Results of a cross-lagged structural equation model

    NARCIS (Netherlands)

    Zacher, Hannes; de Lange, Annet H.

    Future time perspective - the way individuals perceive their remaining time in life - importantly influences socio-emotional goals and motivational outcomes. Recently, researchers have called for studies that investigate relationships between personality and future time perspective. Using a

  6. 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

  7. 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.

  8. 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

  9. 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…

  10. 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...

  11. 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.

  12. Application of real-time global media monitoring and 'derived questions' for enhancing communication by regulatory bodies: the case of human papillomavirus vaccines.

    Science.gov (United States)

    Bahri, Priya; Fogd, Julianna; Morales, Daniel; Kurz, Xavier

    2017-05-02

    The benefit-risk balance of vaccines is regularly debated by the public, but the utility of media monitoring for regulatory bodies is unclear. A media monitoring study was conducted at the European Medicines Agency (EMA) concerning human papillomavirus (HPV) vaccines during a European Union (EU) referral procedure assessing the potential causality of complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) reported to the authorities as suspected adverse reactions. To evaluate the utility of media monitoring in real life, prospective real-time monitoring of worldwide online news was conducted from September to December 2015 with inductive content analysis, generating 'derived questions'. The evaluation was performed through the validation of the predictive capacity of these questions against journalists' queries, review of the EMA's public statement and feedback from EU regulators. A total of 4230 news items were identified, containing personal stories, scientific and policy/process-related topics. Explicit and implicit concerns were identified, including those raised due to lack of knowledge or anticipated once more information would be published. Fifty derived questions were generated and categorised into 12 themes. The evaluation demonstrated that providing the media monitoring findings to assessors and communicators resulted in (1) confirming that public concerns regarding CRPS and POTS would be covered by the assessment; (2) meeting specific information needs proactively in the public statement; (3) predicting all queries from journalists; and (4) altering the tone of the public statement with respectful acknowledgement of the health status of patients with CRSP or POTS. The study demonstrated the potential utility of media monitoring for regulatory bodies to support communication proactivity and preparedness, intended to support trusted safe and effective vaccine use. Derived questions seem to be a familiar and effective

  13. 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

  14. 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

  15. 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...

  16. The past, present, and future of the U.S. electric power sector: Examining regulatory changes using multivariate time series approaches

    Science.gov (United States)

    Binder, Kyle Edwin

    The U.S. energy sector has undergone continuous change in the regulatory, technological, and market environments. These developments show no signs of slowing. Accordingly, it is imperative that energy market regulators and participants develop a strong comprehension of market dynamics and the potential implications of their actions. This dissertation contributes to a better understanding of the past, present, and future of U.S. energy market dynamics and interactions with policy. Advancements in multivariate time series analysis are employed in three related studies of the electric power sector. Overall, results suggest that regulatory changes have had and will continue to have important implications for the electric power sector. The sector, however, has exhibited adaptability to past regulatory changes and is projected to remain resilient in the future. Tests for constancy of the long run parameters in a vector error correction model are applied to determine whether relationships among coal inventories in the electric power sector, input prices, output prices, and opportunity costs have remained constant over the past 38 years. Two periods of instability are found, the first following railroad deregulation in the U.S. and the second corresponding to a number of major regulatory changes in the electric power and natural gas sectors. Relationships among Renewable Energy Credit prices, electricity prices, and natural gas prices are estimated using a vector error correction model. Results suggest that Renewable Energy Credit prices do not completely behave as previously theorized in the literature. Potential reasons for the divergence between theory and empirical evidence are the relative immaturity of current markets and continuous institutional intervention. Potential impacts of future CO2 emissions reductions under the Clean Power Plan on economic and energy sector activity are estimated. Conditional forecasts based on an outlined path for CO2 emissions are

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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)

  10. 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

  11. Inferring Broad Regulatory Biology from Time Course Data: Have We Reached an Upper Bound under Constraints Typical of In Vivo Studies?

    Directory of Open Access Journals (Sweden)

    Saurabh Vashishtha

    Full Text Available There is a growing appreciation for the network biology that regulates the coordinated expression of molecular and cellular markers however questions persist regarding the identifiability of these networks. Here we explore some of the issues relevant to recovering directed regulatory networks from time course data collected under experimental constraints typical of in vivo studies. NetSim simulations of sparsely connected biological networks were used to evaluate two simple feature selection techniques used in the construction of linear Ordinary Differential Equation (ODE models, namely truncation of terms versus latent vector projection. Performance was compared with ODE-based Time Series Network Identification (TSNI integral, and the information-theoretic Time-Delay ARACNE (TD-ARACNE. Projection-based techniques and TSNI integral outperformed truncation-based selection and TD-ARACNE on aggregate networks with edge densities of 10-30%, i.e. transcription factor, protein-protein cliques and immune signaling networks. All were more robust to noise than truncation-based feature selection. Performance was comparable on the in silico 10-node DREAM 3 network, a 5-node Yeast synthetic network designed for In vivo Reverse-engineering and Modeling Assessment (IRMA and a 9-node human HeLa cell cycle network of similar size and edge density. Performance was more sensitive to the number of time courses than to sample frequency and extrapolated better to larger networks by grouping experiments. In all cases performance declined rapidly in larger networks with lower edge density. Limited recovery and high false positive rates obtained overall bring into question our ability to generate informative time course data rather than the design of any particular reverse engineering algorithm.

  12. 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

  13. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

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

  14. Regulatory Governance

    DEFF Research Database (Denmark)

    Kjær, Poul F.; Vetterlein, Antje

    2018-01-01

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

  15. 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)

  16. 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...

  17. The RNA-mediated, asymmetric ring regulatory mechanism of the transcription termination Rho helicase decrypted by time-resolved nucleotide analog interference probing (trNAIP).

    Science.gov (United States)

    Soares, Emilie; Schwartz, Annie; Nollmann, Marcello; Margeat, Emmanuel; Boudvillain, Marc

    2014-08-01

    Rho is a ring-shaped, ATP-dependent RNA helicase/translocase that dissociates transcriptional complexes in bacteria. How RNA recognition is coupled to ATP hydrolysis and translocation in Rho is unclear. Here, we develop and use a new combinatorial approach, called time-resolved Nucleotide Analog Interference Probing (trNAIP), to unmask RNA molecular determinants of catalytic Rho function. We identify a regulatory step in the translocation cycle involving recruitment of the 2'-hydroxyl group of the incoming 3'-RNA nucleotide by a Rho subunit. We propose that this step arises from the intrinsic weakness of one of the subunit interfaces caused by asymmetric, split-ring arrangement of primary RNA tethers around the Rho hexamer. Translocation is at highest stake every seventh nucleotide when the weak interface engages the incoming 3'-RNA nucleotide or breaks, depending on RNA threading constraints in the Rho pore. This substrate-governed, 'test to run' iterative mechanism offers a new perspective on how a ring-translocase may function or be regulated. It also illustrates the interest and versatility of the new trNAIP methodology to unveil the molecular mechanisms of complex RNA-based systems. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. 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.

  19. 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...

  20. Quantification and determinants of the amount of respiratory syncytial virus (RSV shed using real time PCR data from a longitudinal household study [version 2; referees: 2 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Miriam Wathuo

    2017-03-01

    Full Text Available Background A better understanding of respiratory syncytial virus (RSV epidemiology requires realistic estimates of RSV shedding patterns, quantities shed, and identification of the related underlying factors. Methods RSV infection data arise from a cohort study of 47 households with 493 occupants, in coastal Kenya, during the 2009/2010 RSV season. Nasopharyngeal swabs were taken every 3 to 4 days and screened for RSV using a real time polymerase chain reaction (PCR assay. The amount of virus shed was quantified by calculating the ‘area under the curve’ using the trapezoidal rule applied to rescaled PCR cycle threshold output. Multivariable linear regression was used to identify correlates of amount of virus shed. Results The median quantity of virus shed per infection episode was 29.4 (95% CI: 15.2, 54.2 log10 ribonucleic acid (RNA copies * days. Young age (<1 year, presence of upper respiratory symptoms, intra-household acquisition of infection, an individual’s first infection episode in the RSV season, and having a co-infection of RSV group A and B were associated with increased amount of virus shed. Conclusions The findings provide insight into which groups of individuals have higher potential for transmission, information which may be useful in designing RSV prevention strategies.

  1. 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...

  2. 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...

  3. Timely referral saves the lives of mothers and newborns: Midwifery led continuum of care in marginalized teagarden communities – A qualitative case study in Bangladesh [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Animesh Biswas

    2018-03-01

    Full Text Available Background: Prompt and efficient identification, referral of pregnancy related complications and emergencies are key factors to the reduction of maternal and newborn morbidity and mortality. As a response to this critical need, a midwifery led continuum of reproductive health care was introduced in five teagardens in the Sylhet division, Bangladesh during 2016. Within this intervention, professional midwives provided reproductive healthcare to pregnant teagarden women in the community.  This study evaluates the effect of the referral of pregnancy related complications. Methods: A qualitative case study design by reviewing records retrospectively was used to explore the effect of deploying midwives on referrals of pregnancy related complications from the selected teagardens to the referral health facilities in Moulvibazar district of the Sylhet division during 2016.  In depth analyses was also performed on 15 randomly selected cases to understand the facts behind the referral. Results: Out of a total population of 450 pregnant women identified by the midwives, 72 complicated mothers were referred from the five teagardens to the facilities. 76.4% of mothers were referred to conduct delivery at facilities, and 31.1% of them were referred with the complication of prolonged labour. Other major complications were pre-eclampsia (17.8%, retention of the placenta with post-partum hemorrhage (11.1% and premature rupture of the membrane (8.9%. About 60% of complicated mothers were referred to the primary health care centre, and among them 14% of mothers were delivered by caesarean section. 94% deliveries resulted in livebirths and only 6% were stillbirths. Conclusions: This study reveals that early detection of pregnancy complications by skilled professionals and timely referral to a facility is beneficial in saving the majority of baby’s as well as mother’s lives in resource-poor teagardens with a considerable access barrier to health facilities.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. Assessment of regulatory effectiveness. Peer discussions on regulatory practices

    International Nuclear Information System (INIS)

    1999-09-01

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

  10. 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...

  11. 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...

  12. 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...

  13. 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.

  14. 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)

  15. 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

  16. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  17. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of bench-marking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  18. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  19. 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.

  20. Studying Dynamic Features in Myocardial Infarction Progression by Integrating miRNA-Transcription Factor Co-Regulatory Networks and Time-Series RNA Expression Data from Peripheral Blood Mononuclear Cells.

    Directory of Open Access Journals (Sweden)

    Hongbo Shi

    Full Text Available Myocardial infarction (MI is a serious heart disease and a leading cause of mortality and morbidity worldwide. Although some molecules (genes, miRNAs and transcription factors (TFs associated with MI have been studied in a specific pathological context, their dynamic characteristics in gene expressions, biological functions and regulatory interactions in MI progression have not been fully elucidated to date. In the current study, we analyzed time-series RNA expression data from peripheral blood mononuclear cells. We observed that significantly differentially expressed genes were sharply up- or down-regulated in the acute phase of MI, and then changed slowly until the chronic phase. Biological functions involved at each stage of MI were identified. Additionally, dynamic miRNA-TF co-regulatory networks were constructed based on the significantly differentially expressed genes and miRNA-TF co-regulatory motifs, and the dynamic interplay of miRNAs, TFs and target genes were investigated. Finally, a new panel of candidate diagnostic biomarkers (STAT3 and ICAM1 was identified to have discriminatory capability for patients with or without MI, especially the patients with or without recurrent events. The results of the present study not only shed new light on the understanding underlying regulatory mechanisms involved in MI progression, but also contribute to the discovery of true diagnostic biomarkers for MI.

  1. 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...

  2. 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 ...

  3. 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 ...

  4. 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

  5. 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)

  6. 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

  7. 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...

  8. 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...

  9. 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...

  10. 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.

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. Poet Marion Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-North Manchester, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable

  19. Poet Portland Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves the petition, with modifications, from Poet Biorefining-Portland, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel

  20. Poet North Manchester Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-North Manchester, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable

  1. Poet Alexandria Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-Alexandria, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel

  2. Poet Laddonia Approval

    Science.gov (United States)

    This update Auugust 9, 2016 letter from EPA approves with modifications, the petition from Poet Biorefining Laddonia, Poet Laddonia Facility, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act f

  3. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  4. Drugs Approved for Leukemia

    Science.gov (United States)

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  5. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  6. Premarket Approvals (PMA)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Premarket approval by FDA is the required process of scientific review to ensure the safety and effectiveness of all devices classified as Class III devices. An...

  7. 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

  8. The steroidogenic response and corpus luteum expression of the steroidogenic acute regulatory protein after human chorionic gonadotropin administration at different times in the human luteal phase.

    Science.gov (United States)

    Kohen, Paulina; Castro, Olga; Palomino, Alberto; Muñoz, Alex; Christenson, Lane K; Sierralta, Walter; Carvallo, Pilar; Strauss, Jerome F; Devoto, Luigi

    2003-07-01

    This study was designed 1) to assess corpus luteum (CL) steroidogenesis in response to exogenous human chorionic gonadotropin (hCG) at different times during the luteal phase, 2) to examine the effect of hCG on steroidogenic acute regulatory protein (StAR) expression within the CL, 3) to correlate StAR expression and luteal steroidogenic responses to hCG, and 4) to determine whether endogenous LH regulates ovarian steroidogenesis in the early luteal phase. Blood was collected before and after hCG treatment for steroid and hCGbeta determinations. CL were obtained at the time of surgery to assess StAR gene and protein expression. During the early luteal phase various women received the GnRH antagonist for 24-48 h; some of them also received hCG 24 h after the GnRH antagonist. A slight steroidogenic response to hCG was observed in early luteal phase; 17alpha-hydroxyprogesterone, but not progesterone (P4), levels were significantly increased 8 h post-hCG, indicating a differential response by the granulosa and theca-lutein cells. The 1.6- and 4.4-kb StAR transcripts and the 37-kDa preprotein and 30-kDa mature StAR protein did not change post-hCG administration in early luteal phase CL. In contrast, the StAR 4.4- and 1.6-kb transcripts diminished significantly (P < 0.05) after the antagonist treatment. Immunohistochemical staining for StAR protein was weak, particularly in granulosa-lutein cells. Treatment with hCG restored StAR mRNA and protein and plasma P4 levels within 24 h in antagonist-treated women. hCG stimulated the highest plasma concentrations of P4 and estradiol in the midluteal phase, indicating its greatest steroidogenic capacity. Midluteal tissue StAR gene and protein expression increased by 1.6- and 1.4-fold after 24 h of hCG treatment, respectively. Administration of hCG resulted in the greatest increment in plasma P4 (4-fold) and 17alpha-hydroxyprogesterone (3-fold) levels over baseline in the late luteal phase. This was associated with an increase in

  9. 30 CFR 902.10 - State regulatory program approval.

    Science.gov (United States)

    2010-07-01

    ... Mining and Water Management, 3601 C Street, Suite 800, Anchorage, AK 99503-5925, Telephone: (907) 762... Section 902.10 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE ALASKA § 902.10 State...

  10. Shifting paradigm of maternal and perinatal death review system in Bangladesh: A real time approach to address sustainable developmental goal 3 by 2030 [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Animesh Biswas

    2017-07-01

    Full Text Available Recently, Bangladesh has made remarkable progress in reducing maternal and neonatal morality, even though the millennium developmental goal to reduce maternal and neonatal mortality was not achieved. Sustainable Developmental Goal (SDG 3 has already been set for a new target to reduce maternal and neonatal deaths by 2030. The country takes this timely initiative to introduce a maternal and perinatal death review system. This review will discuss the shifting paradigm of the maternal and perinatal death review system in Bangladesh and its challenges in reaching the SDG on time. This review uses existing literature on the maternal and perinatal death review system in Bangladesh, and other systems in similar settings, as well as reports, case studies, news, government letters and meeting minutes. Bangladesh introduced the maternal and perinatal death review system in 2010. Prior to this there was no such comprehensive death review system practiced in Bangladesh. The system was established within the government health system and has brought about positive effects and outcomes. Therefore, the Ministry of Health and Family Welfare of Bangladesh gradually scaled up the maternal and perinatal death review system nationwide in 2016 within the government health system. The present death review system highlighted real-time data use, using the district health information software(DHIS-2. Health mangers are able to take remedial action plans and implement strategies based on findings in DHIS-2. Therefore, effective utilization of data can play a pivotal role in the reduction of maternal and perinatal deaths in Bangladesh. Overall, the maternal and perinatal death review system provides a great opportunity to achieve the SDG 3 on time. However, the system needs continuous monitoring at different levels to ensure its quality and validity of information, as well as effective utilization of findings for planning and implementation under a measureable

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. Vedolizumab: first global approval.

    Science.gov (United States)

    Poole, Raewyn M

    2014-07-01

    Vedolizumab [Entyvio(®) (US, Europe)], a humanized monoclonal antibody α4β7 integrin receptor antagonist, has been developed by Millennium Pharmaceuticals (d/b/a Takeda Pharmaceuticals International) for the treatment of ulcerative colitis and Crohn's disease. Vedolizumab has received its first global approval for the treatment of ulcerative colitis and Crohn's disease in the US, for use in adult patients with moderate-to-severe disease who have had an inadequate response, loss of response or intolerance to one or more standard therapies (corticosteroids, immunomodulators or tumour necrosis factor-α inhibitor) or demonstrated dependence on corticosteroids. Vedolizumab has since been approved for ulcerative colitis and Crohn's disease in the EU, Norway, Iceland and Liechtenstein. This article summarizes the milestones in the development of vedolizumab leading to its first approval for the treatment of ulcerative colitis and Crohn's disease.

  17. 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.

  18. 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

  19. 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)

  20. 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

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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)

  10. CORN, LP Goldfield Approval

    Science.gov (United States)

    This November 19, 2015 letter from EPA approves the petition from CORN, LP, Goldfield facility, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6) RINs under the RFS pro

  11. Poet Fostoria Approval

    Science.gov (United States)

    This August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-Fostoria, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6)

  12. Poet Lake Crystal Approval

    Science.gov (United States)

    This September 19, 2016 letter from EPA approves the petition from Poet Biorefining-Lake Crystal, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6) RINs under the RFS

  13. Poet Leipsic Approval

    Science.gov (United States)

    This August 9, 2016 letter from EPA approves,wtih modifications, the petition from Poet Biorefining-Leipsic, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6) RINs

  14. Drugs Approved for Rhabdomyosarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for rhabdomyosarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries. There may be drugs used in rhabdomyosarcoma that are not listed here.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Development and Validation of a P-35S, T-nos, T-35S and P-FMV Tetraplex Real-time PCR Screening Method to Detect Regulatory Genes of Genetically Modified Organisms in Food.

    Science.gov (United States)

    Eugster, Albert; Murmann, Petra; Kaenzig, Andre; Breitenmoser, Alda

    2014-10-01

    In routine analysis screening methods based on real-time PCR (polymerase chain reaction) are most commonly used for the detection of genetically modified (GM) plant material in food and feed. Screening tests are based on sequences frequently used for GM development, allowing the detection of a large number of GMOs (genetically modified organisms). Here, we describe the development and validation of a tetraplex real-time PCR screening assay comprising detection systems for the regulatory genes Cauliflower Mosaic Virus 35S promoter, Agrobacterium tumefaciens nos terminator, Cauliflower Mosaic Virus 35S terminator and Figwort Mosaic Virus 34S promoter. Three of the four primer and probe combinations have already been published elsewhere, whereas primers and probe for the 35S terminator have been developed in-house. Adjustment of primer and probe concentrations revealed a high PCR sensitivity with insignificant physical cross-talk between the four detection channels. The sensitivity of each PCR-system is sufficient to detect a GMO concentration as low as 0.05% of the containing respective element. The specificity of the described tetraplex is high when tested on DNA from GM maize, soy, rapeseed and tomato. We also demonstrate the robustness of the system by inter-laboratory tests. In conclusion, this method provides a sensitive and reliable screening procedure for the detection of the most frequently used regulatory elements present in GM crops either authorised or unauthorised for food.

  20. 77 FR 1524 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2012-01-10

    ... initiating and adjudicating various types of actions, including disciplinary, eligibility, expedited, and... also may review the decision. Oral Argument in Review of Proceedings FINRA Rule 9341(a) establishes the procedure for a party requesting an oral argument before the Subcommittee or, if applicable, the Extended...

  1. 75 FR 8771 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-02-25

    ... information relative to such member's financial condition as disclosed in its most recent balance sheet... an alternative means of satisfying the requirement that members make balance sheet information... financial condition as disclosed in its most recent balance sheet * * *.'' FINRA proposed providing members...

  2. 75 FR 32525 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-06-08

    ...., Associate Clinical Professor of Law, Cornell Law School, and Director, Cornell Securities Law Clinic, and Lennie Sliwinski, Cornell Law School class of 2011, dated May 15, 2010; and Scott R. Shewan, President... arbitration award to a customer. FINRA Rule 9554 allows FINRA to bring expedited actions to address failures...

  3. 77 FR 55519 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2012-09-10

    ... option, derivative, security-based swap, or other financial instrument overlying a security that is the... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67774; File No. SR-FINRA-2012-025] Self... National Association of Securities Dealers, Inc. (``NASD'')) filed with the Securities and Exchange...

  4. 75 FR 8772 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-02-25

    ... broker-customer relationship; or (5) the lending arrangement is based on a business relationship outside of the broker-customer relationship. In addition, with the exception of lending arrangements between... for a loan that is not the product of the broker- customer relationship would not vitiate the idea...

  5. 75 FR 61793 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-10-06

    ...-ROM, DVD, portable hard drive, laptop computer, disc, diskette, or any other portable device for... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63016; File No. SR-FINRA-2010-021] Self... to Amend FINRA Rule 8210 to Require Information Provided via Portable Media Device be Encrypted...

  6. 75 FR 11972 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-03-12

    ... Business Member's Web site may not reflect 100 percent of that member's volume for that ATS dark pool...' Web sites to see the total volume for any given ATS dark pool, and the TRF Business Members will make... they receive for each ATS dark pool on their Web site and must prominently disclose that the Web site...

  7. 75 FR 56608 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-09-16

    ... Counsel, Secretary, Chief Compliance Officer, Accenture plc to Elizabeth M. Murphy, Secretary, Commission..., Accenture plc to Elizabeth M. Murphy, Secretary, Commission, dated June 3, 2010; and Letter from Karrie... criticized various aspects of the application of the proposed rule change to ETPs. One commenter described...

  8. 77 FR 15824 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2012-03-16

    ... provides that a claim alleging employment discrimination, including sexual harassment, in violation of a... proposed rule change, the Commission has considered the rule's impact on efficiency, competition, and...

  9. 78 FR 57916 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2013-09-20

    ... McLarty, President, American Association for Justice, dated July 11, 2013 (``AAJ Letter''); Katrina M... and General Counsel, Financial Services Institute, dated July 11, 2013 (``FSI Letter''); Glenn S... are not limited to the documents enumerated in the Lists. It would also stress that the Customer Code...

  10. 75 FR 3270 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2010-01-20

    ... fingerprinting requirements of SEA Rule 17f-2 for purposes of a criminal background check. The Commission finds..., competition, and capital formation. 15 U.S.C. 78c(f). \\9\\ 15 U.S.C. 78o-3(b)(6). It is therefore ordered...

  11. 76 FR 81551 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-12-28

    ... the member to qualify for the No-Knowledge Exception in Supplementary Material .02 to FINRA Rule 5320... from trading that security on the same side of the market for its own proprietary account at a price... order up to the size and at a price that is the same as, or better, than the price at which the member...

  12. 75 FR 39603 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-07-09

    ... related to fraud or securities laws violations; \\10\\ (4) a government authority or regulator has provided... related to fraud or securities laws violations; \\14\\ (4) a government authority or regulator has provided... potentially violating an anti-fraud rule of the Federal securities laws and stated that where it has actual...

  13. 75 FR 44033 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the...

    Science.gov (United States)

    2010-07-27

    ... the allowance for research in straightforward and streamlined fashion. Proposed FINRA Rule 5141.03 is... NASD provisions in more straightforward and streamlined fashion and accordingly render them obsolete... and reports concerning issuers, industries, securities, economic factors and trends, portfolio...

  14. 75 FR 30453 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-06-01

    ... reflect the corporate name change and other similar matters. The proposed amendments to the NASD Dispute... Name and Other Technical Changes FINRA proposed to implement certain other non-substantive changes to....'' FINRA also proposed to amend Article II, section 2.1 to change the name and address of the registered...

  15. 77 FR 67038 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2012-11-08

    ... of Functions by FINRA to Subsidiaries (``Delegation Plan''), the NAMC has the power and authority... such other powers and authority as is necessary to effectuate the purposes of FINRA's Rules.\\7\\ The... knowledge. [T]hen the situation could be deemed a legal case.'' The Commission believes that the commenter...

  16. 78 FR 58580 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2013-09-24

    ..., dated July 10, 2013 (``Speyer Letter''); and Leonard Steiner, Attorney, dated July 10, 2013 (``Steiner..., Neuman Letter, Sanders Letter, Speyer Letter, St. John's Law Letter, and Steiner Letter. \\13\\ See... Letter, and Steiner Letter. See also Pace Law Letter. \\15\\ See Bakhtiari Letter and Sanders Letter. \\16...

  17. 78 FR 21449 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2013-04-10

    ... & Kantas, dated Feb. 7, 2013 (``Shepherd Letter''); letter from Leonard Steiner, Beverly Hills, California, dated Feb. 7, 2013 (``Steiner Letter''); letter from Joseph Fogel, Fogel & Associates, dated Feb. 7...

  18. 77 FR 27262 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2012-05-09

    ... University Law School, and Director, Cornell Securities Law Clinic, and Brenda Beauchamp, Cornell Law School... letter from Jill I. Gross, Director, Edward Pekarek, Assistant Director, and Genavieve Shingle, Student..., scheduling, and traveling to hearings; (3) it would provide an alternative for customers who are unable to...

  19. 76 FR 70190 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-11-10

    ... October 20, 2011 (``Shatto Letter''); letter from Naphtali M. Hamlet, Investor, dated October 21, 2011 (``Hamlet Letter''); letter from Daniel Zinn, General Counsel, OTC Markets Group Inc., dated October 20... reported for public dissemination. \\12\\ See Shatto Letter; Hamlet Letter. \\13\\ See Shatto Letter. \\14\\ See...

  20. 76 FR 10629 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2011-02-25

    ... through the eligibility proceedings as ``contrary to the most basic ideals of constitutional due process..., Section 3(b) of the FINRA By-Laws provides that no person shall be associated with a member, continue to... Article III, Section 4 of the FINRA By- Laws, a person is subject to a ``disqualification'' with respect...

  1. 78 FR 29190 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the...

    Science.gov (United States)

    2013-05-17

    ... able to manually input and verify trade data within 10 seconds.\\18\\ One commenter asserted that the... balance between promoting the goals of increased automation and efficiency in the marketplace and... trades with a large number of securities.\\28\\ \\28\\ See FIF Letter and SIFMA Letter. FINRA responded that...

  2. 78 FR 72951 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2013-12-04

    ... regarding the risks and financial impact associated with the customer's loan of securities, and requires... the introducing member that has a customer relationship with the lender in making the determination... securities, and the risks and financial impact associated with the customer's loan of securities. Proposed...

  3. 76 FR 5850 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2011-02-02

    ... certain information relating to customer accounts, including, among other things, the signature of the registered representative introducing the account and signature of the member, partner, officer or manager... clarify that members maintain the signature of the partner, officer or manager denoting that the account...

  4. 78 FR 38771 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2013-06-27

    ... information that raises significant identity theft, personal safety, or privacy concerns that are not... raises personal safety or privacy concerns is released to the public when considering whether to release... customer information or information that raises identity theft, personal safety or privacy concerns that do...

  5. 75 FR 51147 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the...

    Science.gov (United States)

    2010-08-18

    ... ``participation in a public offering'' means for purposes of the Rule and suggested an alternative definition... understood and that the alternative definition suggested by the commenter would be an inappropriate narrowing... underwriter'' under the Rule. FINRA recognized the issue raised by the commenter and stated their intention to...

  6. 75 FR 41562 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2010-07-16

    ... SEC Rule 15c3-3) in the Consolidated FINRA Rulebook July 12, 2010. I. Introduction On May 14, 2010... arrangements) that when computing charges against net capital for transactions in securities covered by FINRA... computed using the applicable special maintenance margin requirements pursuant to other provisions of the...

  7. 75 FR 37488 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2010-06-29

    ... restrictions on sub-penny pricing in theory, it stated that the minimum quoting increments for shares priced... institutional investors looking to take sizeable positions in thinly traded stocks, as the displaying of a...

  8. 76 FR 11542 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-03-02

    ... Surety Association of America. Under NYSE Rule 319(a), the Stockbrokers Partnership Bond and the Brokers... disadvantage to underwriters that do not offer this type of coverage.\\26\\ The commenter further stated that...

  9. 78 FR 60982 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2013-10-02

    ... becomes ``systemic as well as intentional or willful.'' In response, FINRA noted that inclusion of a rule... the rules of a Registered Securities Association enforce compliance with, and provide appropriate... FINRA should only consider a member's activity a rule violation if the violation becomes systemic as...

  10. Linaclotide: first global approval.

    Science.gov (United States)

    McWilliams, Vanessa; Whiteside, Glenn; McKeage, Kate

    2012-11-12

    Linaclotide is a once-daily, orally administered, first-in-class agonist of guanylate cyclase-C that is minimally absorbed. It is being developed to treat gastrointestinal disorders by Ironwood Pharmaceuticals and its partners, Forest Laboratories (North America), Almirall (Europe) and Astellas Pharma (Asia-Pacific). Linaclotide has received its first global approval in the US for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation (CIC), and a marketing submission has been filed in the EU for IBS-C. This article summarizes the milestones in the development of linaclotide leading to this first approval for IBS-C and CIC. This profile has been extracted and modified from the Adis R&D Insight drug pipeline database. Adis R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

  11. Neratinib: First Global Approval.

    Science.gov (United States)

    Deeks, Emma D

    2017-10-01

    Neratinib (Nerlynx™) is an oral, irreversible inhibitor of the human epidermal growth factor receptors HER1 (EGFR), HER2 and HER4. The drug originally arose from research by Wyeth (now Pfizer) and is now being developed by Puma Biotechnology primarily for the treatment of HER2-positive (HER+) breast cancer. Neratinib is approved in the USA for the extended adjuvant treatment of patients with HER2+ early-stage breast cancer who have been previously treated with a trastuzumab-based adjuvant regimen, and is in the preregistration phase for this indication in the EU. Neratinib, as monotherapy and/or combination therapy, is also in phase 3 development for metastatic breast cancer and in phase 1/2 development for advanced breast cancer and other solid tumours, including non-small cell lung cancer, colorectal cancer and glioblastoma. This article summarizes the milestones in the development of neratinib leading to this first approval for breast cancer.

  12. Professional and Regulatory Search

    Science.gov (United States)

    Professional and Regulatory search are designed for people who use EPA web resources to do their job. You will be searching collections where information that is not relevant to Environmental and Regulatory professionals.

  13. 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)

  14. 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.

  15. Future nuclear regulatory challenges

    International Nuclear Information System (INIS)

    Royen, J.

    1998-01-01

    In December 1996, the NEA Committee on Nuclear Regulatory Activities concluded that changes resulting from economic deregulation and other recent developments affecting nuclear power programmes have consequences both for licensees and regulatory authorities. A number of potential problems and issues which will present a challenge to nuclear regulatory bodies over the next ten years have been identified in a report just released. (author)

  16. 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

  17. 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

  18. 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...

  19. 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...

  20. 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.

  1. 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

  2. The regulatory dynamic

    International Nuclear Information System (INIS)

    Dybwad, C.

    2001-01-01

    An outline of the activities and efforts expanded by the National Energy Board to adjust to the changing natural gas market was provided in this presentation. The author began by defining the role of the National Energy Board in energy markets. It must ensure the adoption of rules and procedures that result in a more competitive and efficient market. Light-handed regulatory techniques are the norm, and the National Energy Board is now committed to facilitating the availability and flow of information so that all parties know where opportunities exist, the terms offered to buy or sell goods and services, their quality and costs. It will specialize in providing new participants with information on the workings of the market, who the players are, the regulatory processes in place, and how, when and where the market can be accessed. The manner in which the Board deals with information was reviewed, providing examples along the way to clarify some points. Some of the documents produced by the National Energy Board are being reviewed with the intent of making them easier to read and understand. Audio streaming over the Internet is another avenue being pursued to ensure individuals can listen in real time to hearings without having to be present in the room. The National Energy Board is also exploring alternative dispute resolution techniques. Consultation with energy market participants represents another facet of these efforts to be more accessible and responsive

  3. 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

  4. 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

  5. Regulatory activities; Actividades regulatorias

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

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

  6. 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

  7. 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)

  8. Supercollider: Footprint approved

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    With the 'footprint' - the precise location of the 87-kilometre US Superconducting Supercollider, SSC, and its ancillary buildings - now approved, teams of specialists commissioned by the State of Texas swing into action to procure the 17,000 acres (69 million square metres) of land covered by the project. With the SSC Laboratory in Ellis County and the US Department of Energy (DoE, the overseeing government agency) both hiring manpower for this project to collide 20 TeV (20,000 GeV) proton beams before the end of the century, the host State of Texas is providing a helping hand

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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)

  17. Research and regulatory review

    International Nuclear Information System (INIS)

    Macleod, J.S.; Fryer, D.R.H.

    1979-01-01

    To enable the regulatory review to be effectively undertaken by the regulatory body, there is a need for it to have ready access to information generated by research activities. Certain advantages have been seen to be gained by the regulatory body itself directly allocating and controlling some portion of these activities. The princial reasons for reaching this conclusion are summarised and a brief description of the Inspectorates directly sponsored programme outlined. (author)

  18. 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

  19. Regulatory Commission of Alaska

    Science.gov (United States)

    Map Help Regulatory Commission of Alaska Login Forgot Password Arrow Image Forgot password? View Cart login Procedures for Requesting Login For Consumers General Information Telephone Electric Natural Gas

  20. Regulation No. 56/2006 Coll. of the Nuclear Regulatory Authority of the Slovak Republic dated as of January 12, 2006 on details concerning requirements for quality system documentation of authorisation holder, as well as details concerning quality requirements for nuclear installations, details concerning quality requirements for classified equipment and details concerning the scope of their approval

    International Nuclear Information System (INIS)

    2006-01-01

    This Regulation provides details of the requirements for quality system documentation holder, details of the quality requirements for nuclear installations, details concerning quality requirements for classified equipment and details of the scope of their approval. This Regulation came into force on March 1, 2006.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. The Evolution of Approval Services.

    Science.gov (United States)

    Warzala, Martin

    1994-01-01

    Describes major developments in book approval plans used by academic libraries for acquisition and for information dissemination and document distribution services based on approval-like concepts. Topics addressed include publishers; marketing; the impact of library automation; value-added services; the economic climate; the influence of…

  6. 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

  7. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-10-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  8. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  9. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-01-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  10. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1991-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  11. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-08-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  12. Trust in regulatory regimes

    NARCIS (Netherlands)

    Six, Frédérique; Verhoest, Koen

    2017-01-01

    Within political and administrative sciences generally, trust as a concept is contested, especially in the field of regulatory governance. This groundbreaking book is the first to systematically explore the role and dynamics of trust within regulatory regimes. Conceptualizing, mapping and analyzing

  13. Nuclear Regulatory legislation

    International Nuclear Information System (INIS)

    1984-06-01

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

  14. 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

  15. Improving nuclear regulatory effectiveness

    International Nuclear Information System (INIS)

    2001-01-01

    Ensuring that nuclear installations are operated and maintained in such a way that their impact on public health and safety is as low as reasonably practicable has been and will continue to be the cornerstone of nuclear regulation. In the past, nuclear incidents provided the main impetus for regulatory change. Today, economic factors, deregulation, technological advancements, government oversight and the general requirements for openness and accountability are leading regulatory bodies to review their effectiveness. In addition, seeking to enhance the present level of nuclear safety by continuously improving the effectiveness of regulatory bodies is seen as one of the ways to strengthen public confidence in the regulatory systems. This report covers the basic concepts underlying nuclear regulatory effectiveness, advances being made and future requirements. The intended audience is primarily nuclear safety regulators, but government authorities, nuclear power plant operators and the general public may also be interested. (author)

  16. [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.

  17. Regulatory risk coherence

    International Nuclear Information System (INIS)

    Remick, F.J.

    1992-01-01

    As one of the most progressive users of risk assessment in decision making, the US Nuclear Regulatory Commission (NRC) is in a position to play an important role in influencing the development of standard government wide policies for the application of risk assessment in decision making. The NRC, with the support of the nuclear industry, should use the opportunity provided by its experience with risk assessment to actively encourage the adoption of standard national and international health-based safety goals and at the same time accelerate its own efforts to implement the safety goals it has already developed for itself. There are signs of increased recognition of the need for consistency and coherence in the application of risk assessment in government decision making. The NRC and the nuclear industry have recently taken a great step toward establishing a consistant and coherent risk assessment-based culture in the US nuclear industry. As a result of Generic Letter 88-20, which asks each commercial nuclear power plant licensee to perform an individual plant examination by September 1992, for the first time a risk assessment characterizing initiating events in each plant will exist

  18. 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

  19. Regulatory guidance document

    International Nuclear Information System (INIS)

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM's evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7

  20. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

  1. Managing Regulatory Body Competence

    International Nuclear Information System (INIS)

    2013-01-01

    In 2001, the IAEA published TECDOC 1254, which examined the way in which the recognized functions of a regulatory body for nuclear facilities results in competence needs. Using the systematic approach to training (SAT), TECDOC 1254 provided a framework for regulatory bodies for managing training and developing and their maintaining their competence. It has been successfully used by many regulators. The IAEA has also introduced a methodology and an assessment tool - Guidelines for Systematic Assessment of Regulatory Competence Needs (SARCoN) - which provides practical guidance on analysing the training and development needs of a regulatory body and, through a gap analysis, guidance on establishing competence needs and how to meet them. In 2009, the IAEA established a steering committee (supported by a bureau) with the mission to advise the IAEA on how it could best assist Member States to develop suitable competence management systems for their regulatory bodies. The committee recommended the development of a safety report on managing staff competence as an integral part of a regulatory body's management system. This Safety Report was developed in response to this request. It supersedes TECDOC 1254, broadens its application to regulatory bodies for all facilities and activities, and builds upon the experience gained through the application of TECDOC 1254 and SARCoN and the feedback received from Member States. This Safety Report applies to the management of adequate competence as needs change, and as such is equally applicable to the needs of States 'embarking' on a nuclear power programme. It also deals with the special case of building up the competence of regulatory bodies as part of the overall process of establishing an 'embarking' State's regulatory system

  2. 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....

  3. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2016-01-01

    - Poland: Organisation and structure; 7 - Slovak Republic: International co-operation, Nuclear security (Entry into force of the Amendment to the Convention on the Physical Protection of Nuclear Material; Act No. 91/2016 Coll. on Criminal Responsibility of Legal Persons), Liability and compensation (Newly adopted Civil Procedural Code); 8 - Slovenia: Nuclear safety and radiological protection - including nuclear emergency planning (Decree on the program of the systematic monitoring of working and living environments and raising awareness about measures to reduce public exposure to natural radiation sources; Rules on authorised experts for radiation and nuclear safety); 9 - United States: General legislation, regulations and instruments (Nuclear Regulatory Commission approved a final rule amending licensing, inspection and annual fee regulations to establish a variable annual fee structure for light-water small modular reactors)

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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

  3. 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...

  4. 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...

  5. 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

  6. 48 CFR 750.7105 - Approving authorities.

    Science.gov (United States)

    2010-10-01

    ... CONTRACT MANAGEMENT EXTRAORDINARY CONTRACTUAL ACTIONS Extraordinary Contractual Actions To Protect Foreign Policy Interests of the United States 750.7105 Approving authorities. All authority to approve actions...

  7. 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

  8. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-10-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  9. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-04-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  10. Through the regulatory hoop

    International Nuclear Information System (INIS)

    Kirner, N.P.

    1985-01-01

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

  11. Drugs Approved for Esophageal Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for esophageal cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  12. Drugs Approved for Liver Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for liver cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  13. Drugs Approved for Kaposi Sarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Kaposi sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  14. Drugs Approved for Pancreatic Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  15. Drugs Approved for Vaginal Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) to prevent vaginal cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  16. Drugs Approved for Skin Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for skin cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  17. Drugs Approved for Vulvar Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for vulvar cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  18. Drugs Approved for Wilms Tumor

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Wilms tumor and other childhood kidney cancers. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  19. Drugs Approved for Lung Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for lung cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  20. Drugs Approved for Bone Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bone cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  1. Drugs Approved for Malignant Mesothelioma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  2. Drugs Approved for Penile Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for penile cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  3. Drugs Approved for Bladder Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bladder cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  4. Drugs Approved for Endometrial Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  5. Is It Really FDA Approved?

    Science.gov (United States)

    ... satisfaction before companies can market them in interstate commerce. Some examples of biologics that require approval are ... it means the agency has determined that the benefits of the product outweigh the known risks for ...

  6. Electronic Voucher Approval - Financial Management

    Data.gov (United States)

    US Agency for International Development — This process provides a workflow and eSignature capability which allows the CFO to router vouchers for review and electronic signature approval to COTRs in AIDW. It...

  7. 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

  8. 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.'

  9. 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

  10. 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)

  11. Regulatory Office for Network Industries

    International Nuclear Information System (INIS)

    2005-01-01

    The main goal of the economic regulation of network industries is to ensure a balance between the interests of consumers and investors and to encourage providing high-quality goods and services. The task of the regulatory authority is to protect the interests of consumers against monopolistic behaviour of regulated enterprises. At the same time, the regulatory office has to protect the interests of investors by giving them an opportunity to achieve an adequate return on their investments. And last, but not least, the regulatory office has to provide regulated enterprises with appropriate incentives to make them function in an efficient and effective manner and to guarantee the security of delivery of energies and related services. All this creates an efficient regulatory framework that is capable of attracting the required amount and type of investments. This also means providing third party access to the grids, the opening of energy markets, the un-bundling of accounts according to production, distribution, transmission and other activities and the establishment of a transparent and stable legislative environment for regulated companies, investors and consumers. Otherwise, in the long run consumers may suffer from a serious deterioration of service quality, although in the short run they are protected against increased prices. Under the Act No. 276/2001 Coll. on Regulation of Network Industries and on amendment of some acts the Office for Regulation of Network Industries has been commissioned to implement the main objectives of regulation of network industries. By network industries the Act No. 276/2001 Coll. on Regulation means the following areas: (a) Production, purchase, transit and distribution of electricity; (b) Production, purchase, transit and distribution of gas; (c) Production, purchase and distribution of heat; (d) Water management activities relating to the operation of the public water supply system or the public sewerage system; (e) Water management

  12. Perceptions of regulatory approaches

    International Nuclear Information System (INIS)

    Halin, Magnus; Leinonen, Ruusaliisa

    2012-01-01

    Ms. Ruusaliisa Leinonen and Mr. Magnus Halin from Fortum gave a joint presentation on industry perceptions of regulatory oversight of LMfS/SC. It was concluded that an open culture of discussion exists between the regulator (STUK) and the licensee, based on the common goal of nuclear safety. An example was provided of on how regulatory interventions helped foster improvements to individual and collective dose rate trends, which had remained static. Regulatory interventions included discussions on the ALARA concept to reinforce the requirement to continuously strive for improvements in safety performance. Safety culture has also been built into regulatory inspections in recent years. Training days have also been organised by the regulatory body to help develop a shared understanding of safety culture between licensee and regulatory personnel. Fortum has also developed their own training for managers and supervisors. Training and ongoing discussion on LMfS/SC safety culture is considered particularly important because both Fortum and the regulatory body are experiencing an influx of new staff due to the demographic profile of their organisations. It was noted that further work is needed to reach a common understanding of safety culture on a practical level (e.g., for a mechanic setting to work), and in relation to the inspection criteria used by the regulator. The challenges associated with companies with a mix of energy types were also discussed. This can make it more difficult to understand responsibilities and decision making processes, including the role of the parent body organisation. It also makes communication more challenging due to increased complexity and a larger number of stakeholders

  13. 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

  14. ELECTRONIC COMPLIANCE AND APPROVAL PROJECT (ECAP)

    Energy Technology Data Exchange (ETDEWEB)

    Hope Morgan; Richard A. Varela; Deborah LaHood; Susan Cisco; Mary Ann Benavides; Donna Burks

    2002-11-01

    The Texas Railroad Commission (RRC), working in partnership with the United States Department of Energy and the oil and gas industry it regulates, is implementing a strategy for improving efficiency in regulations and significantly reducing administrative operating costs through the Electronic Compliance and Approval Process (ECAP). The project will streamline regulatory compliance and reporting by providing the ability to electronically submit, process, and query oil and gas applications and reports through the Internet-based ECAP system. Implementation of an ECAP drilling permit pilot project began September 1999 after funding resources were secured--a $700,000 grant from the U.S. Department of Energy and an appropriation of $1.4 million from the Texas Legislature. The pilot project involves creating the ability to file, review, and approve a well's drilling permit application through a completely electronic process. The pilot project solution will ultimately provide the infrastructure, technology, and electronic modules to enable the filing of all compliance permits and performance reports through the internet from a desktop computer. The pilot project was conducted in three phases. The first phase, implemented May 2000, provided the infrastructure that allows the electronic filing and approval of simple drilling permit applications, associated fees, and attachments. The official ''roll-out'' of ECAP and the first electronically filed drilling permit application occurred on May 11, 2000 in Dallas in conjunction with an Internet Workshop sponsored by the Petroleum Technology Transfer Council. After the completion of Phase I, the ECAP team conducted an extensive review of progress to date and analyzed requirements and opportunities for future steps. The technical team identified core infrastructure modifications that would facilitate and better support future development and expansion of the ECAP system and work began on database structure

  15. Nuclear regulatory decision making

    International Nuclear Information System (INIS)

    Wieland, Patricia; Almeida, Ivan Pedro Salati de

    2011-01-01

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

  16. The US regulatory framework

    International Nuclear Information System (INIS)

    MacDonald, C.E.

    1984-01-01

    The chapter discusses the following: a brief account is given of the regulations covering the transportation of radioactive materials in the USA; departmental responsibilities; design of casks; packaging; approval of routes for transport of spent fuel; physical protection against theft or sabotage; inspection; safety standards. (U.K.)

  17. Nuclear Regulatory Legislation

    International Nuclear Information System (INIS)

    1989-08-01

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

  18. 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')

  19. 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)

  20. Regulatory and licensee surveys

    International Nuclear Information System (INIS)

    2009-01-01

    Prior to the workshop two CSNI/WGHOF surveys were distributed. One survey was directed at regulatory bodies and the other was directed at plant licensees. The surveys were: 1 - Regulatory Expectations of Licensees' Arrangements to Ensure Suitable Organisational Structure, Resources and Competencies to Manage Safety (sent to WGHOF regulatory members). The survey requested that the respondents provide a brief overview of the situation related to plant organisations in their country, their regulatory expectations and their formal requirements. The survey addressed three subjects: the demonstration and documentation of organisational structures, resources and competencies, organisational changes, issues for improvement (for both current and new plants). Responses were received from eleven regulatory bodies. 2 - Approaches to Justify Organisational Suitability (sent to selected licensees). The purpose of the survey to was to gain an understanding of how licensees ensure organisational suitability, resources and competencies. This information was used to assist in the development of the issues and subjects that were addressed at the group discussion sessions. Responses were received from over fifteen licensees from nine countries. The survey requested that the licensees provide information on how they ensure effective organisational structures at their plants. The survey grouped the questions into the following four categories: organisational safety functions, resource and competence, decision-making and communication, good examples and improvement needs. The findings from these surveys were used in conjunction with other factors to identify the key issues for the workshop discussion sessions. The responses from these two surveys are discussed briefly in Sections 4 and 5 of this report. More extensive reviews of the regulatory and licensee responses are provided in Appendix 1

  1. 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.

  2. Rationales for regulatory activity

    Energy Technology Data Exchange (ETDEWEB)

    Perhac, R.M. [Univ. of Tennessee, Knoxville, TN (United States)

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  3. 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

  4. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2001-01-01

    These columns treat of the legislative and regulatory activities of different OECD countries: Australia (environment protection and biodiversity conservation act and regulations, 1999-2000); Bulgaria (basic standards for radiation protection, 2000); France (decree on the standard tax charged on polluting activities due from operators of installations classified for environmental protection purposes, 2000; amendment of the orders on the transport of dangerous goods by road and by rail, 2000); Georgia (law on nuclear and radiation safety, 1998); Germany (amendments to nuclear legislation implementing EURATOM directives, 2000; amendment to the nuclear third party liability provisions of the atomic energy act, 2001; amendment to the foreign trade ordinance, 2000; ordinance on the treatment of foodstuffs with radiation, 2000; general administrative regulations on radioactivity limits in food and feeds); Ireland (European communities regulations on foodstuffs treated with ionizing radiations, 2000); Japan (law for nuclear sitting area development, 2000; Republic of Korea (amendments to the act on compensation for nuclear damage, 2001); Latvia (act on radiation safety and nuclear safety, 2000); Lithuania (resolution approving the decommissioning program for Unit 1, Ignalina NPP, 2001); Luxembourg (grand-ducal regulations on the protection of the public against the risks resulting from ionizing radiation, 2000; grand-ducal regulations relating to foods and food ingredients treated with ionizing radiation, 2000); Mexico (norm regarding selection, qualification and training requirements for staff of a NPP, 2000; norm regarding solid residue as radioactive waste, 2000); Mongolia (law on nuclear weapons free status and its implementing resolution, 2000); Netherlands (amendment to the nuclear energy act, 2000); Norway (act on radiation and use of radiation, 2000); Pakistan (nuclear authority ordinance, 2001); Poland (atomic energy act, 2000); Spain (royal decree on activities

  5. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2013-01-01

    This section reviews the recent National legislative and regulatory activities: Algeria (Establishment of a nuclear security centre); Armenia (Amendment to the Law of the Republic of Armenia on the Safe Utilization of Atomic Energy for Peaceful Purposes); Brazil (creation of a Support Centre for Safety and Radiation Protection - Centro de Apoio a Seguranca Fisica Nuclear e Radiologica - CENASF); Canada (enacting of the Nuclear Terrorism Act,4 which amends the Criminal Code, creating four new Criminal Code offences related to nuclear terrorism; proposal to replace the existing Nuclear Liability Act with the increase of the amount of compensation available to address civil nuclear damage); France (National plan for the management of radioactive materials and waste - PNGMDR; Law No.2013-580 of 4 July 2013 authorising approval of the agreement between France and Monaco on the management of Monegasque radioactive waste in the French territory; Decree No.2013-675 of 25 July 2013 publishing an agreement of co-operation between France and Saudi Arabia for the development of nuclear energy for peaceful purposes); Germany (Act for retrieving radioactive waste from and decommissioning the Asse II Mine); Greece (Decree transposing Council Directive 2011/70/Euratom); Ireland (Adoption of European Communities Regulations on Carriage of Dangerous Goods by Road and Use of Transportable Pressure Equipment); Luxembourg (Transposition of Council Directive 2011/70/Euratom of 19 July 2011 establishing a Community framework for the responsible and safe management of spent fuel and radioactive waste); Poland (New requirements for employees concerning radiological protection; New detailed requirements for nuclear facility siting, design, commissioning and operation, organisational unit commissioning, periodical safety assessment, decommissioning and fund contributions; New regulation on subsidies related to nuclear safety and radiological protection; New requirements on transparency of

  6. 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.

  7. Developing regulatory approaches

    International Nuclear Information System (INIS)

    Axelsson, Lars

    2012-01-01

    Lars Axelsson presented SSM progress on oversight of LMfS/SC since the Chester 1 Workshop in 2007. Current SSM approaches for safety culture oversight include targeted safety management and safety culture inspections, compliance inspections which cover aspects of safety management/safety culture and multi-disciplinary team inspections. Examples of themes for targeted inspections include management of ambiguous operational situations or other weak signals, understanding of and attitudes to Human Performance tools, the Safety Department's role and authority and Leadership for safety. All regulatory activities provide inputs for the SSM yearly safety evaluation of each licensee. A form has been developed to capture safety culture observations from inspections and other interactions with licensees. Analysis will be performed to identify patterns and provide information to support planning of specific Safety Culture activities. Training has been developed for regulatory staff to enhance the quality of regulatory interventions on safety culture. This includes a half-day seminar to provide an overview of safety culture, and a workshop which provides more in-depth discussion on cultural issues and how to capture those during regulatory activities. Future plans include guidance for inspectors, and informal seminars on safety culture with licensees

  8. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1992-07-01

    This document compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rule making which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  9. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-02-01

    This document is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considered action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  10. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1989-07-01

    This document is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  11. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1992-11-01

    This document provides a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  12. Comments on regulatory reform

    International Nuclear Information System (INIS)

    Hendrie, J.M.

    1982-01-01

    Nuclear regulatory reform is divided into two parts. The first part contains all those matters for which new legislation is required. The second part concerns all those matters that are within the power of the Commission under existing statutes. Recommendations are presented

  13. Comments on regulatory reform

    Energy Technology Data Exchange (ETDEWEB)

    Hendrie, J.M.

    1982-01-01

    Nuclear regulatory reform is divided into two parts. The first part contains all those matters for which new legislation is required. The second part concerns all those matters that are within the power of the Commission under existing statutes. Recommendations are presented.

  14. 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

  15. Drugs Approved for Cervical Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for cervical cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  16. Drugs Approved for Multiple Myeloma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for multiple myeloma and other plasma cell neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  17. Drugs Approved for Testicular Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for testicular cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  18. Drugs Approved for Hodgkin Lymphoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Hodgkin lymphoma. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  19. Drugs Approved for Myeloproliferative Neoplasms

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for myeloproliferative neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  20. 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.