Sample records for gained regulatory approval

  1. 7 CFR 1710.105 - State regulatory approvals.

    Code of Federal Regulations, 2010 CFR

    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...

  2. 76 FR 66344 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  3. 75 FR 5157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  4. 76 FR 25397 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-04

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change To Amend the By- Laws of FINRA Regulation, Inc. With Regard to District Committees April 28, 2011. I. Introduction On February 25, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the...

  5. 75 FR 6422 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... Incorporated NYSE Rule 411(a)(ii)(5) as Part of the Process of Developing the Consolidated FINRA Rulebook February 2, 2010. On December 4, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a...

  6. Developing regulatory strategy for microbicides.

    PubMed

    Nardi, Ronald; Arterburn, Linda; Carlton, Lisa

    2014-01-01

    Ever since the discovery that a virus was responsible for AIDS, prevention of HIV infection has been a drug/vaccine development target in therapeutic research. Microbicide products are a viable, globally applicable option; however, to date, no product has been approved anywhere in the world. Development of such a product will need to account for the changing disease landscape and will need to leverage available regulatory pathways to gain approvals in the developed world and emerging markets. In countries where the regulatory pathway is not clear which is the case in several emerging markets, sponsors will need to employ a flexible approach to gather and meet local regulatory requirements and ultimately gain product approvals.

  7. Regulatory approval of new medical devices: cross sectional study.

    PubMed

    Marcus, Hani J; Payne, Christopher J; Hughes-Hallett, Archie; Marcus, Adam P; Yang, Guang-Zhong; Darzi, Ara; Nandi, Dipankar

    2016-05-20

     To investigate the regulatory approval of new medical devices.  Cross sectional study of new medical devices reported in the biomedical literature.  PubMed was searched between 1 January 2000 and 31 December 2004 to identify clinical studies of new medical devices. The search was carried out during this period to allow time for regulatory approval.  Articles were included if they reported a clinical study of a new medical device and there was no evidence of a previous clinical study in the literature. We defined a medical device according to the US Food and Drug Administration as an "instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article."  Type of device, target specialty, and involvement of academia or of industry for each clinical study. The FDA medical databases were then searched for clearance or approval relevant to the device.  5574 titles and abstracts were screened, 493 full text articles assessed for eligibility, and 218 clinical studies of new medical devices included. In all, 99/218 (45%) of the devices described in clinical studies ultimately received regulatory clearance or approval. These included 510(k) clearance for devices determined to be "substantially equivalent" to another legally marketed device (78/99; 79%), premarket approval for high risk devices (17/99; 17%), and others (4/99; 4%). Of these, 43 devices (43/99; 43%) were actually cleared or approved before a clinical study was published.  We identified a multitude of new medical devices in clinical studies, almost half of which received regulatory clearance or approval. The 510(k) pathway was most commonly used, and clearance often preceded the first published clinical study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. 75 FR 41254 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62476; File No. SR-FINRA-2010-012] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a Proposed Rule Change To Amend FINRA Rule 8312 (FINRA BrokerCheck Disclosure) July 8, 2010. I. Introduction On March 30, 2010, the Financial Industry Regulatory...

  9. 77 FR 55519 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-10

    ...\\ and Rule 19b-4 thereunder,\\2\\ a proposed rule change to adopt existing NASD Interpretive Material... Policy The proposed rule change would replace several existing provisions in the Front Running Policy...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change...

  10. 78 FR 58580 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-24

    ... proposed rule change, FINRA would no longer require a customer to elect one of the two existing panel...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change...,\\2\\ a proposed rule change amending the Code of Arbitration Procedure for Customer Disputes...

  11. 78 FR 21449 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-10

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... ``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ a proposed rule change to amend FINRA's Customer and Industry... arbitrator'' in the Codes. Specifically, the proposed rule change would (a) exclude persons associated with a...

  12. 30 CFR 931.15 - Approval of New Mexico regulatory program amendments.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Approval of New Mexico regulatory program..., DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE NEW MEXICO § 931.15 Approval of New Mexico regulatory program amendments. The following is a list of the dates...

  13. 30 CFR 931.15 - Approval of New Mexico regulatory program amendments.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Approval of New Mexico regulatory program..., DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE NEW MEXICO § 931.15 Approval of New Mexico regulatory program amendments. The following is a list of the dates...

  14. 30 CFR 931.15 - Approval of New Mexico regulatory program amendments.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Approval of New Mexico regulatory program..., DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE NEW MEXICO § 931.15 Approval of New Mexico regulatory program amendments. The following is a list of the dates...

  15. 30 CFR 931.15 - Approval of New Mexico regulatory program amendments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Approval of New Mexico regulatory program..., DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE NEW MEXICO § 931.15 Approval of New Mexico regulatory program amendments. The following is a list of the dates...

  16. 75 FR 43588 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  17. 78 FR 69168 - Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  18. 7 CFR 1710.105 - State regulatory approvals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... (3) Loans for the purpose of assisting borrowers to implement demand side management and energy conservation programs and on and off grid renewable energy systems. (b) At minimum, in the case of all loans in... to obtain approval of a project or its financing from a state regulatory authority, RUS may require...

  19. 7 CFR 1710.105 - State regulatory approvals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... (3) Loans for the purpose of assisting borrowers to implement demand side management and energy conservation programs and on and off grid renewable energy systems. (b) At minimum, in the case of all loans in... to obtain approval of a project or its financing from a state regulatory authority, RUS may require...

  20. 7 CFR 1710.105 - State regulatory approvals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... (3) Loans for the purpose of assisting borrowers to implement demand side management and energy conservation programs and on and off grid renewable energy systems. (b) At minimum, in the case of all loans in... to obtain approval of a project or its financing from a state regulatory authority, RUS may require...

  1. 7 CFR 1710.105 - State regulatory approvals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... (3) Loans for the purpose of assisting borrowers to implement demand side management and energy conservation programs and on and off grid renewable energy systems. (b) At minimum, in the case of all loans in... to obtain approval of a project or its financing from a state regulatory authority, RUS may require...

  2. 77 FR 74722 - Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-17

    ... to approve a proposed rule change of a self-regulatory organization if it finds that such proposed... 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...

  3. 77 FR 15432 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-15

    ... directs the Commission to approve a proposed rule change of a self-regulatory organization if it finds... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66560; File No. SR-OCC-2012-01] Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule Change Relating to Public...

  4. 77 FR 40394 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-09

    ... to approve a proposed rule change of a self-regulatory organization if it finds that such proposed... 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...

  5. 30 CFR 948.15 - Approval of West Virginia regulatory program amendments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... amendments. 948.15 Section 948.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT... approving all or portions of those amendments in the Federal Register, and the State statutory or regulatory... to those final rules identify and discuss any assumptions underlying approval, any conditions placed...

  6. 30 CFR 902.10 - State regulatory program approval.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false State regulatory program approval. 902.10 Section 902.10 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE..., Technical Library, 1999 Broadway, Suite 3320, Denver, Colorado 80202-5733. [60 FR 33724, June 29, 1995, as...

  7. 78 FR 59401 - Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-26

    ...\\ directs the Commission to approve a proposed rule change of a self-regulatory organization if it finds... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70464; File No. SR-ICEEU-2013-11] Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change Related To Enhanced...

  8. 49 CFR 173.471 - Requirements for U.S. Nuclear Regulatory Commission approved packages.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Requirements for U.S. Nuclear Regulatory...) Materials § 173.471 Requirements for U.S. Nuclear Regulatory Commission approved packages. In addition to the applicable requirements of the U.S. Nuclear Regulatory Commission (NRC) and other requirements of...

  9. 49 CFR 173.471 - Requirements for U.S. Nuclear Regulatory Commission approved packages.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Requirements for U.S. Nuclear Regulatory...) Materials § 173.471 Requirements for U.S. Nuclear Regulatory Commission approved packages. In addition to the applicable requirements of the U.S. Nuclear Regulatory Commission (NRC) and other requirements of...

  10. 49 CFR 173.471 - Requirements for U.S. Nuclear Regulatory Commission approved packages.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Requirements for U.S. Nuclear Regulatory...) Materials § 173.471 Requirements for U.S. Nuclear Regulatory Commission approved packages. In addition to the applicable requirements of the U.S. Nuclear Regulatory Commission (NRC) and other requirements of...

  11. 49 CFR 173.471 - Requirements for U.S. Nuclear Regulatory Commission approved packages.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Requirements for U.S. Nuclear Regulatory...) Materials § 173.471 Requirements for U.S. Nuclear Regulatory Commission approved packages. In addition to the applicable requirements of the U.S. Nuclear Regulatory Commission (NRC) and other requirements of...

  12. [Regulatory Framework for Approval of PET Drug in Korea: A Survey Report].

    PubMed

    Kurihara, Chieko; Inoue, Tomio

    2015-11-01

    To identify regulatory framework for approval of PET drugs in Korea. Interview and literature survey. In Korea Good Manufacturing Practice (GMP) regulation specific to radiopharmaceuticals, including PET (Positron Emission Tomography) drugs, under the Pharmaceutical Affairs Act was issued in August 2014, to be enforced on July 1, 2015, and its guidance was issued in December 2014. The new facilities to be established after July 1 of 2015 have to be compatible with this new regulation and already established facilities have two years grace period until June 30 of 2017. During this period, the regulatory authority will inspect all of the production sites which hold or submit approvals of radiopharmaceuticals. As of September 2015 in Korea, there are 7 commercial companies and 15 hospitals and institutes, which have approvals of PET drugs mainly FDG, and these companies and/or hospitals can supply PET drugs outside institutions. In this article we introduce the Korean regulations of development and approval of radiopharmaceuticals. The Korean regulatory authorization policy for radiopharmaceuticals are to some extent similar to the policy which the U.S. regulators set as the new regulations of PET drug. It is expected that the situations of production sites in Korea are to be improved through actual discussions among regulators and PET community through the process of actual inspection.

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

    Code of Federal Regulations, 2010 CFR

    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. Regulatory review time and post-market safety events for novel medicines approved by the EMA between 2001 and 2010: a cross-sectional study

    PubMed Central

    Zeitoun, Jean-David; Lefèvre, Jérémie H; Downing, Nicholas S; Bergeron, Henri; Ross, Joseph S

    2015-01-01

    Aims Regulatory review time has been associated with post-market medication safety issues in the United States. Our objective was to evaluate whether regulatory review time and near deadline approval are associated with post-market safety events (PMSEs) for novel medicines approved by the European Medicines Agency (EMA). Methods We performed a cross-sectional analysis of all novel medicines approved by the EMA through the centralized authorization procedure between 2001 and 2010. PMSEs were defined as withdrawals and communications identified through Dear Healthcare Professional Communications (DHPCs). Regulatory review time was defined as the time that elapsed between the start of the assessment procedure and approval. Near regulatory deadline approval was defined as approval within the 30 days before the EMA’s 210 day regulatory deadline. Results Among 161 eligible medicines, PMSEs were identified for 49 (30.4%), 44 of which were DHPCs, five of which were withdrawals. Median regulatory review time was 337 days (IQR 276–406) and was not associated with PMSEs (P = 0.57). However, when categorized by regulatory review speed tertile, there were differences in risk of PMSEs, with higher rates among medicines in the middle tertile (25 of 55, 45.4%; P = 0.01). Finally, 26 medicines were approved near the 210 day regulatory deadline, but were not more likely to have PMSEs (38.5% vs. 28.7%; P = 0.32). Conclusions Neither faster EMA regulatory review speed nor approval near regulatory deadlines was associated with greater likelihood of PMSEs among recently approved novel medicines. PMID:25808713

  15. Regulatory review time and post-market safety events for novel medicines approved by the EMA between 2001 and 2010: a cross-sectional study.

    PubMed

    Zeitoun, Jean-David; Lefèvre, Jérémie H; Downing, Nicholas S; Bergeron, Henri; Ross, Joseph S

    2015-10-01

    Regulatory review time has been associated with post-market medication safety issues in the United States. Our objective was to evaluate whether regulatory review time and near deadline approval are associated with post-market safety events (PMSEs) for novel medicines approved by the European Medicines Agency (EMA). We performed a cross-sectional analysis of all novel medicines approved by the EMA through the centralized authorization procedure between 2001 and 2010. PMSEs were defined as withdrawals and communications identified through Dear Healthcare Professional Communications (DHPCs). Regulatory review time was defined as the time that elapsed between the start of the assessment procedure and approval. Near regulatory deadline approval was defined as approval within the 30 days before the EMA's 210 day regulatory deadline. Among 161 eligible medicines, PMSEs were identified for 49 (30.4%), 44 of which were DHPCs, five of which were withdrawals. Median regulatory review time was 337 days (IQR 276-406) and was not associated with PMSEs (P = 0.57). However, when categorized by regulatory review speed tertile, there were differences in risk of PMSEs, with higher rates among medicines in the middle tertile (25 of 55, 45.4%; P = 0.01). Finally, 26 medicines were approved near the 210 day regulatory deadline, but were not more likely to have PMSEs (38.5% vs. 28.7%; P = 0.32). Neither faster EMA regulatory review speed nor approval near regulatory deadlines was associated with greater likelihood of PMSEs among recently approved novel medicines. © 2015 The British Pharmacological Society.

  16. 30 CFR 944.15 - Approval of Utah regulatory program amendments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 816/817.61; 850; Memorandum of Agreement between the Board and Division of Oil, Gas, and Mining and... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Approval of Utah regulatory program amendments..., DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE UTAH § 944...

  17. 30 CFR 944.15 - Approval of Utah regulatory program amendments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 816/817.61; 850; Memorandum of Agreement between the Board and Division of Oil, Gas, and Mining and... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Approval of Utah regulatory program amendments..., DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE UTAH § 944...

  18. 30 CFR 944.15 - Approval of Utah regulatory program amendments.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 816/817.61; 850; Memorandum of Agreement between the Board and Division of Oil, Gas, and Mining and... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Approval of Utah regulatory program amendments..., DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE UTAH § 944...

  19. 30 CFR 944.15 - Approval of Utah regulatory program amendments.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 816/817.61; 850; Memorandum of Agreement between the Board and Division of Oil, Gas, and Mining and... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Approval of Utah regulatory program amendments..., DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE UTAH § 944...

  20. 30 CFR 944.15 - Approval of Utah regulatory program amendments.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 816/817.61; 850; Memorandum of Agreement between the Board and Division of Oil, Gas, and Mining and... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Approval of Utah regulatory program amendments..., DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE UTAH § 944...

  1. Regulatory Approval of Cancer Risk-reducing (Chemopreventive) Drugs: Moving What We Have Learned into the Clinic

    PubMed Central

    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

    2010-01-01

    This paper 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 non-scientists 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. PMID:21372031

  2. 75 FR 82119 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63599; File No. SR-MSRB-2010-16] Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of Amendments to Rule G-5, on Disciplinary Actions by Appropriate Regulatory Agencies, Remedial Notices by Registered Securities Associations; and Rule G-17, on Conduct...

  3. 76 FR 79729 - Self-Regulatory Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-22

    ... plc as signatories. II. Self-Regulatory Organization's Statement of the Terms of Substance of the... approve a proposed rule change of a self-regulatory organization if it finds that such proposed rule... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66001; File No. SR-ICC-2011-03] Self-Regulatory...

  4. 75 FR 43584 - Self-Regulatory Organizations; EDGX Exchange, Inc; Order Approving a Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-26

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62515; File No. SR-EDGX-2010-02] Self-Regulatory Organizations; EDGX Exchange, Inc; Order Approving a Proposed Rule Change Relating to Direct Edge... DE Holdings, and DE Holdings will be the sole stockholder of DEI. The self-regulatory functions of...

  5. 75 FR 43582 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Order Approving a Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-26

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62514; File No. SR-EDGA-2010-02] Self-Regulatory Organizations; EDGA Exchange, Inc.; Order Approving a Proposed Rule Change Relating to Direct Edge... Holdings will be the sole stockholder of DEI. The self-regulatory functions of the Exchange will remain...

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

    PubMed

    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.

  7. Priority review drugs approved by the FDA and the EMA: time for international regulatory harmonization of pharmaceuticals?

    PubMed

    Alqahtani, Saad; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Eguale, Tewodros

    2015-07-01

    The US Food and Drug Administration (FDA) priority review process applies to a drug that is considered a significant improvement over the available alternatives. The European Medicines Agency (EMA) accelerated approval applies to a product that is of major public health interest. This study assessed differences in the characteristics of priority review new molecular entities and new therapeutic biologic products approved by the FDA and the EMA. This study includes regulatory information on drug applications, approvals, indications, and orphan designations of all priority review drugs approved by the FDA and the EMA in the period 1999-2011. Descriptive statistics, t-tests, and chi-squared and Wilcoxon tests were performed. Overall, 100 FDA priority review new molecular entities and new therapeutic biologics were approved by both agencies; 87.0% of the products were first approved by the FDA. The average FDA review time (9.2 ± 8.4 months) was significantly lower than the EMA average review time (14.6 ± 4.0 months) (p < 0.0001). The FDA and the EMA granted orphan designation to 43.0% and 33.0%, respectively, of the applications. There were differences in the administration route (1.0% of all products), dosage (8.0%), strength (23%), posology (51.0%), indications (30.0%), restrictions of use (52.0%), limitations of use (19.0%), and outcomes limitations (28.0%) approved by both regulatory agencies. Significant differences exist in the characteristics of the priority review drugs approved by the FDA and the EMA. Harmonization of the US and European regulatory frameworks may facilitate timely approval of pharmaceutical products. Copyright © 2015 John Wiley & Sons, Ltd.

  8. 76 FR 28257 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-16

    ...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving Proposed Rule Change To Modify Chapter... Commission received no comment letters regarding the proposal. This order approves the proposed rule change... for imbalance and indicative data dissemination; (4) clarify when an Order Imbalance Indicator is...

  9. Efficacy, Safety, and Regulatory Approval of Food and Drug Administration-Designated Breakthrough and Nonbreakthrough Cancer Medicines.

    PubMed

    Hwang, Thomas J; Franklin, Jessica M; Chen, Christopher T; Lauffenburger, Julie C; Gyawali, Bishal; Kesselheim, Aaron S; Darrow, Jonathan J

    2018-04-24

    Purpose The breakthrough therapy program was established in 2012 to expedite the development and review of new medicines. We evaluated the times to approval, efficacy, and safety of breakthrough-designated versus non-breakthrough-designated cancer drugs approved by the US Food and Drug Administration (FDA). Methods We studied all new cancer drugs approved by the FDA between January 2012 and December 2017. Regulatory and therapeutic characteristics (time to FDA approval, pivotal trial efficacy end point, novelty of mechanism of action) were compared between breakthrough-designated and non-breakthrough-designated cancer drugs. Random-effects meta-regression was used to assess the association between breakthrough therapy designation and hazard ratios for progression-free survival (PFS), response rates (RRs) for solid tumors, serious adverse events, and deaths not attributed to disease progression. Results Between 2012 and 2017, the FDA approved 58 new cancer drugs, 25 (43%) of which received breakthrough therapy designation. The median time to first FDA approval was 5.2 years for breakthrough-designated drugs versus 7.1 years for non-breakthrough-designated drugs (difference, 1.9 years; P = .01). There were no statistically significant differences between breakthrough-designated and non-breakthrough-designated drugs in median PFS gains (8.6 v 4.0 months; P = .11), hazard ratios for PFS (0.43 v 0.51; P = .28), or RRs for solid tumors (37% v 39%; P = .74). Breakthrough therapy-designated drugs were not more likely to act via a novel mechanism of action (36% v 39%; P = 1.00). Rates of deaths (6% v 4%; P = .99) and serious adverse events (38% v 36%; P = 0.93) were also similar in breakthrough-designated and non-breakthrough-designated drugs. Conclusion Breakthrough-designated cancer drugs were associated with faster times to approval, but there was no evidence that these drugs provide improvements in safety or novelty; nor was there a statistically significant efficacy

  10. 78 FR 54349 - Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-03

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70263; File No. SR-NSCC-2013-09] Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed Rule Change.... On July 2, 2013, the National Securities Clearing Corporation filed with the Securities and Exchange...

  11. 75 FR 55836 - Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62849; File No. SR-NSCC-2010-07] Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed Rule Change To... September 3, 2010. I. Introduction On July 1, 2010, National Securities Clearing Corporation (``NSCC...

  12. 75 FR 26822 - Self-Regulatory Organizations; Order Approving Minor Rule Violation Plan for EDGX Exchange, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... Commission adopted amendments to paragraph (c) of Rule 19d-1 to allow self-regulatory organizations (``SROs... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62036; File No. 4-594] Self-Regulatory Organizations; Order Approving Minor Rule Violation Plan for EDGX Exchange, Inc. May 5, 2010. On March 19, 2010...

  13. 75 FR 26827 - Self-Regulatory Organizations; Order Approving Minor Rule Violation Plan for EDGA Exchange, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... Commission adopted amendments to paragraph (c) of Rule 19d-1 to allow self-regulatory organizations (``SROs... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62037; File No. 4-595] Self-Regulatory Organizations; Order Approving Minor Rule Violation Plan for EDGA Exchange, Inc. May 5, 2010. On March 19, 2010...

  14. 77 FR 9274 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-16

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66375; File No. SR-CBOE-2011-117] Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving Proposed Rule Change Relating to Its Automated Improvement Mechanism February 10, 2012. On December 14, 2011, the Chicago Board...

  15. 77 FR 21123 - Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-09

    ... unsettled positions in classes of securities such as illiquid municipal or corporate bonds, whose volatility... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66731; File No. SR-NSCC-2012-02] Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed Rule Change To...

  16. 75 FR 13174 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-18

    ...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving Proposed Rule Change To Establish Strike Price Intervals and Trading Hours for Options on Index-Linked Securities March 12, 2010. I. Introduction On January 27, 2010, the Chicago Board Options Exchange, Incorporated (``CBOE...

  17. 78 FR 21460 - Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-10

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69302; File No. SR-NSCC-2012-10] Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed Rule Change To... customers, a more accurate reflection of risks in the calculation of Clearing Fund margin, however, could...

  18. 75 FR 29597 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-26

    ...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving Proposed Rule Change, as Modified by Amendment No. 1 Thereto, To List and Trade CBOE Gold ETF Volatility Index Options May 19, 2010. I. Introduction On March 18, 2010, the Chicago Board Options Exchange, Incorporated (``CBOE...

  19. 76 FR 70207 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-10

    ...-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of Proposed Rule Change Regarding Professional Qualifications and Information Concerning Associated Persons November 3... information concerning associated persons. The proposed rule change was published for comment in the Federal...

  20. 76 FR 16462 - Self-Regulatory Organizations; NASDAQ OMX BX LLC; Order Approving a Proposed Rule Change Relating...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64090; File No. SR-BX-2011-007] Self-Regulatory Organizations; NASDAQ OMX BX LLC; Order Approving a Proposed Rule Change Relating to Permanent Approval of the BX and NES Inbound Routing Relationship March 17, 2011. I. Introduction On January 28, 2011, NASDAQ...

  1. 77 FR 76146 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Approving a Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-26

    ...-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Approving a Proposed Rule Change Consisting of Amendments To Streamline New Issue Information Submission Requirements Under MSRB Rules G-32..., and market information requirements); and the Electronic Municipal Market Access (``EMMA[supreg...

  2. 77 FR 66196 - Self-Regulatory Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  3. 77 FR 26061 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-02

    ...-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of Proposed Rule Change Consisting of Establishment of a Subscription to Historical Information and Documents Submitted to... historical information and documents submitted to the MSRB's Short-Term Obligation Rate Transparency System...

  4. 76 FR 77038 - Self-Regulatory Organizations; Stock Clearing Corporation of Philadelphia; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-09

    .... Second, NASDAQ OMX is proposing to amend the compositional requirements of the Nominating & Governance... approve a proposed rule change of a self-regulatory organization if it finds that such proposed rule... are in the custody or control of such clearing agency or for which it is responsible, and to comply...

  5. 76 FR 77048 - Self-Regulatory Organizations; Boston Stock Exchange Clearing Corporation; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-09

    .... Second, NASDAQ OMX is proposing to amend the compositional requirements of the Nominating & Governance... approve a proposed rule change of a self-regulatory organization if it finds that such proposed rule... are in the custody or control of such clearing agency or for which it is responsible, and to comply...

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

    PubMed

    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.

  7. Gene therapy for cancer: regulatory considerations for approval.

    PubMed

    Husain, S R; Han, J; Au, P; Shannon, K; Puri, R K

    2015-12-01

    The rapidly changing field of gene therapy promises a number of innovative treatments for cancer patients. Advances in genetic modification of cancer and immune cells and the use of oncolytic viruses and bacteria have led to numerous clinical trials for cancer therapy, with several progressing to late-stage product development. At the time of this writing, no gene therapy product has been approved by the United States Food and Drug Administration (FDA). Some of the key scientific and regulatory issues include understanding of gene transfer vector biology, safety of vectors in vitro and in animal models, optimum gene transfer, long-term persistence or integration in the host, shedding of a virus and ability to maintain transgene expression in vivo for a desired period of time. Because of the biological complexity of these products, the FDA encourages a flexible, data-driven approach for preclinical safety testing programs. The clinical trial design should be based on the unique features of gene therapy products, and should ensure the safety of enrolled subjects. This article focuses on regulatory considerations for gene therapy product development and also discusses guidance documents that have been published by the FDA.

  8. Gene therapy for cancer: regulatory considerations for approval

    PubMed Central

    Husain, S R; Han, J; Au, P; Shannon, K; Puri, R K

    2015-01-01

    The rapidly changing field of gene therapy promises a number of innovative treatments for cancer patients. Advances in genetic modification of cancer and immune cells and the use of oncolytic viruses and bacteria have led to numerous clinical trials for cancer therapy, with several progressing to late-stage product development. At the time of this writing, no gene therapy product has been approved by the United States Food and Drug Administration (FDA). Some of the key scientific and regulatory issues include understanding of gene transfer vector biology, safety of vectors in vitro and in animal models, optimum gene transfer, long-term persistence or integration in the host, shedding of a virus and ability to maintain transgene expression in vivo for a desired period of time. Because of the biological complexity of these products, the FDA encourages a flexible, data-driven approach for preclinical safety testing programs. The clinical trial design should be based on the unique features of gene therapy products, and should ensure the safety of enrolled subjects. This article focuses on regulatory considerations for gene therapy product development and also discusses guidance documents that have been published by the FDA. PMID:26584531

  9. 77 FR 5286 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a Proposed Rule Change To Adopt Rules Governing S&P 500 Option Variance Basket Trades January 27, 2012. I. Introduction On October 26, 2011, Chicago Board Options Exchange, Incorporated (``Exchange'' or ``CBOE'') filed...

  10. 77 FR 22027 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a Proposed Rule Change Relating to Stock- Option Orders April 6, 2012. I. Introduction On February 7, 2012, the Chicago Board Options Exchange, Incorporated (``CBOE'' or ``Exchange''), filed with the Securities and Exchange...

  11. 75 FR 2915 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  12. 75 FR 15757 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-30

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61716; File No. SR-CBOE-2010-008] Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a Proposed Rule Change Relating to Co- location Service Fees March 16, 2010. Correction In notice document 2010-6184...

  13. How do patent rights affect regulatory approvals and data exclusivity rights for pharmaceuticals in the EU?

    PubMed

    Bogaert, Peter; Van Keymeulen, Eveline

    2012-09-01

    This article sheds light on the relationship, or rather, absence of a relationship, between patent rights and regulatory approval procedures in the EU. The principle of 'patent linkage' has long been recognized and applied by regulatory authorities in the USA. The European Commission, however, opposes the idea of linking patent rights to marketing authorizations and pricing and reimbursement decisions. This position is grounded in Article 126 of Directive 2001/83 and is expected not to change anytime soon, given the clear reaffirmation thereof in the recent Sector Inquiry Report and Transparency Directive Proposal. Therefore, the European Medicines Agency or national authorities are not permitted to refuse approval and, likely, pricing and reimbursement of a generic when the innovative reference product is still protected by a patent. The authors, however, advocate that there are strong legal arguments for patent holders to challenge regulatory decisions that did not respect their patent rights before the competent national courts.

  14. 77 FR 65433 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Approving a Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-26

    ...-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Approving a Proposed Rule Change To Amend the Real-Time Transaction Reporting System Information System and Subscription Service October 22...'') information system. The proposed rule change was published for comment in the Federal Register on September 12...

  15. 76 FR 40758 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64805; File No. SR-ISE-2011-30] Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed Rule Change Relating to Complex Orders July 5, 2011. I. Introduction On May 23, 2011, the International Securities Exchange, LLC...

  16. 76 FR 64980 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  17. 75 FR 70055 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... SECURITIES AND EXCHANGE COMMISION [Release No. 34-63293; File No. SR-OCC-2010-16] Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule Change Relating to Weekly Options And Monthly Options November 9, 2010. I. Introduction On September 15, 2010, The Options Clearing...

  18. 76 FR 78059 - Self-Regulatory Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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... such as settlement banks and other clearing organizations. See generally Article VIII, Sections 1 and 5...

  19. 75 FR 3950 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-25

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61368; File No. SR-ISE-2009-87] Self-Regulatory... Exchange Act Release No. 61024 (November 18, 2009), 74 FR 61395 (November 24, 2009). II. Description of the...(b)(2) of the Act,\\7\\ that the proposed rule change (SR-ISE-2009-87) be, and hereby is, approved. \\7...

  20. 78 FR 40538 - Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-05

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69890; File No. SR-NSCC-2013-05] Self-Regulatory Organizations; National Securities Clearing Corporation; Order Approving Proposed Rule Change To Require That All Locked-In Trade Data Submitted to It for Trade Recording Be Submitted in Real-time June 28, 2013. I. Introduction On April 30, 2013,...

  1. 77 FR 59427 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-27

    ...-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of a Proposed Rule Change To Amend Rule G-34 on CUSIP Numbers, New Issue, and Market Information Requirements September 21... consisting of amendments to Rule G-34 on CUSIP numbers, new issue, and market information requirements. The...

  2. 76 FR 11533 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Granting Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63955; File No. SR-ISE-2010-73] Self-Regulatory Organizations; International Securities Exchange, LLC; Order Granting Approval of a Proposed Rule Change To Modify Qualified Contingent Cross Order Rules February 24, 2011. I. Introduction On July 14, 2010, the...

  3. 75 FR 59303 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62956; File No. SR-OCC-2010-09] Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of Proposed Rule Change Relating to... clearing organization'' registered as such with the CFTC, OCC also filed this proposed rule change for...

  4. 78 FR 52587 - Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Order Approving and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-23

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70228; File No. 4-663] Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Order Approving and Declaring Effective a Plan..., Inc. and the Topaz Exchange, LLC August 19, 2013. On July 2, 2013, the Financial Industry Regulatory...

  5. 75 FR 76758 - Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Order Approving and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-09

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63430; File No. 4-618] Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Order Approving and Declaring Effective a Plan for the Allocation of Regulatory Responsibilities Between BATS Exchange, Inc., BATS Y-Exchange, Inc., Chicago Board Options Exchange, Inc., Chicago...

  6. 77 FR 4844 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  7. 77 FR 26590 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-04

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66880; File No. SR-ISE-2012-16] Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed Rule Change Relating to Procedures for Executing the Stock Leg(s) of Stock-Option Orders April 30, 2012. I. Introduction On February 29, 2012, the International...

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

    PubMed

    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.

  9. 78 FR 47449 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-05

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70076; File No. SR-OCC-2013-09] Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule Change, as Modified by Amendment No. 1, To Separate the Powers and Duties Currently Combined in the Office of OCC's Chairman Into Two Offices, Chairman and President, an...

  10. 77 FR 30562 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-23

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67013; File No. SR-OCC-2012-04] Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule Change Relating to Stock Loan Buy-In and Sell-Out Rules May 17, 2012. I. Introduction On March 22, 2012, The Options Clearing Corporation (``OCC'') filed with the...

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

    PubMed

    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.

  12. 77 FR 59030 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Granting Approval of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-25

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67888; File No. SR-BATS-2012-030] Self-Regulatory Organizations; BATS Exchange, Inc.; Order Granting Approval of Proposed Rule Change To Amend BATS Rule 14.11, Entitled ``Other Securities'' September 19, 2012. I. Introduction On July 20, 2012, BATS...

  13. 75 FR 30095 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Approving Proposed Rule Amending Its...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  14. 76 FR 20063 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-11

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64181; File No. SR-OCC-2010-19] Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving a Proposed Rule Change Relating to Stock Loan Programs April 5, 2011. I. Introduction On December 16, 2010, The Options Clearing Corporation (``OCC...

  15. 77 FR 4605 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Order Granting Approval of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  16. 75 FR 8769 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change, as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-25

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61545; File No. SR-BATS-2009-032] Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change, as Modified by Amendment No. 1 Thereto, To Amend BATS Fee Schedule To Impose Fees for Physical Ports Used To Connect to BATS...

  17. 78 FR 21996 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Accelerated Approval...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69341; File No. SR-NASDAQ-2013-048] Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Accelerated Approval of a Proposed Rule... in a Limit State or Straddle State, and unlike normal circumstances, may not be a true reflection of...

  18. 75 FR 21688 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Accelerated Approval...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Accelerated Approval of Proposed Rule... 20, 2010. I. Introduction On March 11, 2010, The NASDAQ Stock Market LLC (``Nasdaq'' or ``Exchange.... Strike prices for ETF options are permitted in $1 or greater intervals where the strike price is $200 or...

  19. 77 FR 8927 - Self-Regulatory Organizations; Chicago Stock Exchange, Inc.; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66366; File No. SR-CHX-2011-34] Self-Regulatory Organizations; Chicago Stock Exchange, Inc.; Order Approving a Proposed Rule Change Regarding Suspension of a Participant's Trading Privileges on the Exchange February 9, 2012. I. Introduction On December 16, 2011, the Chicago Stock Exchange, Inc. ...

  20. 75 FR 9987 - Self-Regulatory Organizations; The Depository Trust Company; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-04

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61593; File No. SR-DTC-2009-17] Self-Regulatory Organizations; The Depository Trust Company; Order Approving Proposed Rule Change To Allow The Depository Trust Company To Provide Settlement Services to European Central Counterparty Limited for U.S. Securities Traded on European Trading Venues...

  1. 78 FR 29186 - Self-Regulatory Organizations; The Depository Trust Company; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-17

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69562; File No. SR-DTC-2013-01] Self-Regulatory Organizations; The Depository Trust Company; Order Approving Proposed Rule Change To Modify Its Practice Regarding the Collection of Participants' Required Participants Fund Deposits May 13, 2013. I. Introduction On March 20, 2013, The Depository...

  2. 78 FR 62814 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  3. 75 FR 2899 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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 Listing Fees for Structured Products January 12, 2010. I. Introduction On November 19, 2009, New York...

  4. 78 FR 36616 - Self-Regulatory Organizations; The Depository Trust Company; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69741; File No. SR-DTC-2013-03] Self-Regulatory Organizations; The Depository Trust Company; Order Approving Proposed Rule Change in Connection With the Implementation of The Foreign Account Tax Compliance Act (FATCA) June 12, 2013. On April 22, 2013, The Depository Trust Company (``DTC'') filed...

  5. The US Food and Drug Administration's expedited approval programs: Evidentiary standards, regulatory trade-offs, and potential improvements.

    PubMed

    Wallach, Joshua D; Ross, Joseph S; Naci, Huseyin

    2018-06-01

    The US Food and Drug Administration has several regulatory programs and pathways to expedite the development and approval of therapeutic agents aimed at treating serious or life-debilitating conditions. A common feature of these programs is the regulatory flexibility, which allows for a customized approval approach that enables market authorization on the basis of less rigorous evidence, in exchange for requiring postmarket evidence generation. An increasing share of therapeutic agents approved by the Food and Drug Administration in recent years are associated with expedited programs. In this article, we provide an overview of the evidentiary standards required by the Food and Drug Administration's expedited development and review programs, summarize the findings of the recent academic literature demonstrating some of the limitations of these programs, and outline potential opportunities to address these limitations. Recent evidence suggests that therapeutic agents in the Food and Drug Administration's expedited programs are approved on the basis of fewer and smaller studies that may lack comparator groups and random allocation, and rather than focusing on clinical outcomes for study endpoints, rely instead on surrogate markers of disease. Once on the market, agents receiving expedited approvals are often quickly incorporated into clinical practice, and evidence generated in the postmarket period may not necessarily address the evidentiary limitations at the time of market entry. Furthermore, not all pathways require additional postmarket studies. Evidence suggests that drugs in expedited approval programs are associated with a greater likelihood that the Food and Drug Administration will take a safety action following market entry. There are several opportunities to improve the timeliness, information value, and validity of the pre- and postmarket studies of therapeutic agents receiving expedited approvals. When use of nonrandomized and uncontrolled studies cannot

  6. 76 FR 67783 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change To Amend...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65646, File No. SR-BATS-2011-033] Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change To Amend and Restate the Second Amended and Restated Certificate of Incorporation of BATS Global Markets, Inc. October 27, 2011. I...

  7. 76 FR 55148 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change To Adopt...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  8. 77 FR 48570 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  9. 75 FR 69491 - Self-Regulatory Organizations; Order Approving Proposed Rule Change by New York Stock Exchange...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  10. 77 FR 67851 - Self-Regulatory Organizations; BOX Options Exchange LLC; Order Approving Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  11. 78 FR 75437 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  12. 76 FR 8793 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  13. 76 FR 2182 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  14. 76 FR 52729 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65149; File No. SR-Phlx-2011-89] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule Change Relating to Alpha Index Options August 17, 2011. I. Introduction On June 23, 2011, NASDAQ OMX PHLX LLC (the...

  15. 75 FR 9988 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Granting Approval of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  16. 76 FR 4400 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-25

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63731; File No. SR-BX-2010-083] Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change Relating to the Price Improvement... (``BOX'') to permit an Options Participant initiating a Price Improvement Period (``PIP'') to designate a...

  17. 77 FR 56894 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-14

    ...-Regulatory Organizations; New York Stock Exchange LLC; Order Approving Proposed Rule Change Amending NYSE... 611--Compliant Tool for Floor Brokers September 10, 2012. I. Introduction On July 13, 2012, New York... provide Floor Brokers with a new functionality through which to effect manual cross transactions of block...

  18. 76 FR 79262 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-21

    ...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed Rule Change To... Select Markets December 15, 2011. I. Introduction On August 30, 2011, The NASDAQ Stock Market LLC... Global and Global Select Markets. The proposed rule change was published in the Federal Register on...

  19. 76 FR 71411 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change, as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65728, File No. SR-BATS-2011-035] Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change, as Modified by Partial Amendment No. 1, To Amend and Restate the Amended and Restated Bylaws of BATS Global Markets, Inc. November 10, 2011. I. Introduction On September 7,...

  20. 76 FR 71394 - Self-Regulatory Organizations; The Depository Trust Company; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65721; File No. SR-DTC-2011-07] Self-Regulatory Organizations; The Depository Trust Company; Order Approving a Proposed Rule Change as Modified by Amendment Nos. 1 and 2 Relating To a New Daily Report Subscription for Security Position Reports November 10, 2011. I. Introduction On August 24, 201...

  1. How Data Packages Lacking Phase III Pivotal Trial Data Can Support Regulatory Approval and Reimbursement for Oncologics in Australia.

    PubMed

    Macaulay, Richard; Siddiqui, Mohammad Kashif; Stoddart, Samuel

    2015-05-01

    Oncology drugs lacking supportive phase III trial data have achieved Food and Drug Administration (FDA) and European Medicines Agency (EMA) regulatory approval and even European reimbursement approval where no therapeutic alternative exists and early-stage data indicate dramatic clinical benefits. This research aimed to compare under what circumstances oncologics can obtain both regulatory and reimbursement approval in Australia on this basis. Therapeutic Goods Administration (TGA) Australian Public Assessment Reports, EMA, FDA, and Pharmaceutical Benefits Advisory Committee (PBAC) Public Summary Documents were extracted for any oncologic indication appraised in Australia on a pivotal trial package lacking phase III data, excluding pediatric indications and new formulations. Australian Public Assessment Reports were available for six TGA-appraised oncologics across seven indications on such a data package: five of seven approved, one of seven restricted, and one of seven rejected. The EMA and the FDA issued recommendations on these indications an average of 1 and 2 years earlier, respectively. The PBAC appraised six oncologics across 10 indications on such a data package, with four (nilotinib, dasatinib, imatinib, and brentuximab vedotin) approved and two rejected (cetuximab and bevacizumab). Seven of the eight approved indications required multiple submissions, with inadequate clinical data frequently cited as key. Six of the eight PBAC-approved indications included economic modeling on a cost-benefit approach. The TGA will approve oncologics that offer potentially substantial clinical benefits on the basis of an indirect comparison of single-arm trials but at a delay versus the EMA and the FDA. The PBAC reimbursement approval also requires more rigorous supportive clinical data and acceptable cost-effectiveness as demonstrated on a cost-benefit or cost-quality-adjusted life-year metric. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes

  2. 75 FR 1439 - Self-Regulatory Organizations; NYSE Amex LLC; Order Approving a Proposed Rule Change Rescinding...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ...-Regulatory Organizations; NYSE Amex LLC; Order Approving a Proposed Rule Change Rescinding NYSE Information Memoranda 04-27 and 07-66 and Issuing a New Information Memo Concerning the Exchange's Gap Quote Policy... NYSE Information Memoranda 04-27 and 07-66 and issue a new Information Memo that provides updated...

  3. 77 FR 23294 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving a Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-18

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66808; File No. SR-BATS-2012-013] Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving a Proposed Rule Change To Amend BATS Exchange, Inc. Rule 2.12 To Make Permanent the Pilot Program That Permits BATS Exchange, Inc. To Receive Inbound...

  4. 76 FR 38712 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving a Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-01

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64754; File No. SR-BATS-2011-015] Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving a Proposed Rule Change To Amend BATS Rule 11.9, Entitled ``Orders and Modifiers'' and BATS Rule 11.13, Entitled ``Order Execution'' June 27, 2011. I...

  5. 77 FR 42533 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-19

    ...-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change Amending Its Rules... Ownership Structure of the Exchange July 13, 2012. I. Introduction On May 14, 2012, NYSE Arca, Inc. (``NYSE... Holdings from the ownership structure of the Exchange (the ``Merger''). The proposed rule changes were...

  6. 78 FR 15394 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  7. 75 FR 48391 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Approving a Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-10

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62639; File No. SR-Phlx-2010-89] Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Approving a Proposed Rule Change Relating to Pricing... proposed rule change to establish pricing for 10Gb direct circuit connections and codify pricing for 10Gb...

  8. 75 FR 48390 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-10

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62638; File No. SR-BX-2010-043] Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change Relating to Pricing for Direct... establish pricing for 10Gb direct circuit connections and codify pricing for 1Gb direct circuit connections...

  9. 77 FR 43618 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-25

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67468; File No. SR-NASDAQ-2012-062] Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change To Modify Its Corporate Governance Rules July 19, 2012. I. Introduction On May 17, 2012, The NASDAQ Stock Market LLC...

  10. 78 FR 31993 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving Proposed Rule Change Relating...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-28

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69607; File No. SR-BX-2013-029] Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving Proposed Rule Change Relating to Board of Director Qualifications May 20, 2013. On March 27, 2013, NASDAQ OMX BX, Inc. (``BX'' or ``Exchange'') filed with the...

  11. 77 FR 49034 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... to react to the execution (an effect known as ``market impact'' or ``information leakage''). As a...' shares will avoid the deleterious effect of market impact discussed above and result in overall faster...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change To Amend Rule...

  12. 78 FR 22001 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Accelerated Approval of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69344; File No. SR-Phlx-2013-29] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Accelerated Approval of a Proposed Rule Change... not be a true reflection of the value of the series being quoted. In response to these concerns, the...

  13. 78 FR 42988 - Self-Regulatory Organizations; New York Stock Exchange LLC; NYSE MKT LLC; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-18

    ...-2012-58] Self-Regulatory Organizations; New York Stock Exchange LLC; NYSE MKT LLC; Order Approving... Related Supplementary Material July 12, 2013. I. Introduction On October 26, 2012, the New York Stock... cover the position only pursuant to a new order, which must be time-recorded upstairs and upon receipt...

  14. 75 FR 43217 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change, as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-23

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62524; File No. SR-BATS-2010-008] Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change, as Modified by Amendment No. 1 Thereto, To Amend BATS Rules 2.5 and 17.2 To Establish a Registration Requirement for Principals July 16, 2010. I. Introduction On April 9,...

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

    PubMed

    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.

  16. 77 FR 38877 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-29

    ...-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change, as Modified by...\\ and Rule 19b-4 thereunder,\\2\\ a proposed rule change to allow certain cross trades effected on the...-substantive changes to its rules. The proposed rule change was published for comment in the Federal Register...

  17. 75 FR 1438 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ...-Regulatory Organizations; New York Stock Exchange LLC; Order Approving a Proposed Rule Change Rescinding Information Memoranda 04-27 and 07-66 and Issuing a New Information Memo Concerning the Exchange's Gap Quote... proposed rule change to rescind NYSE Information Memoranda 04-27 and 07-66 and issue a new Information Memo...

  18. 75 FR 12590 - Self-Regulatory Organizations; The Chicago Stock Exchange, Inc.; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  19. 75 FR 20018 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving a Proposed Rule Change, As...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-16

    ... mechanisms for two different prices.\\42\\ NASDAQ OMX then cites two of its own proposed rule changes and...-Regulatory Organizations; BATS Exchange, Inc.; Order Approving a Proposed Rule Change, As Amended, To Offer...\\ thereunder, a proposed rule change to offer certain new Exchange data products to Exchange Members \\3\\ and...

  20. 78 FR 40255 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Order Granting Approval to Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-03

    ...-Regulatory Organizations; BATS Y-Exchange, Inc.; Order Granting Approval to Proposed Rule Change Amending and Restating the Amended and Restated By-Laws of BATS Y-Exchange, Inc. June 27, 2013. I. Introduction On April 29, 2013, BATS Y-Exchange, Inc. (the ``Exchange'' or ``BYX'') filed with the Securities and Exchange...

  1. 78 FR 21982 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Granting Accelerated Approval of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69343; File No. SR-BX-2013-026] Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Granting Accelerated Approval of a Proposed Rule Change To Adopt... not be a true reflection of the value of the series being quoted. In response to these concerns, the...

  2. 77 FR 61649 - Self-Regulatory Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-10

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67970; File No. SR-ICC-2012-12] Self-Regulatory Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To Amend Schedule 502 of the ICE Clear..., 2012. I. Introduction On August 9, 2012, ICE Clear Credit LLC (``ICC'') filed with the Securities and...

  3. 78 FR 4914 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Approving Proposed Rule Change To Amend...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-23

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68574; File No. SR-Phlx-2012-130] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Approving Proposed Rule Change To Amend Performance Evaluations With Respect to Quote Submissions of Streaming Quote Traders and Remote Streaming Quote Traders...

  4. 75 FR 6072 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-05

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61446; File No. SR-NASDAQ-2009-077] Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving Proposed Rule Change To Modify the Procedures Followed When a Listed Company Falls Below Certain Listing Requirements January 29, 2010. I. Introduction On August 17, 2009, The NASDAQ...

  5. 77 FR 26066 - Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-02

    ...-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change to Provide for a T+1 Settlement of the Initial Payment Related to the CDS Contracts Cleared by ICE Clear Europe Limited April 26, 2012. I. Introduction On March 6, 2012, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the...

  6. 75 FR 80553 - Self-Regulatory Organizations; NYSE Amex LLC; Order Approving a Proposed Rule Change Relating to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  7. 75 FR 13629 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-22

    ... contained in Rule 5250(b)(2) that a company must issue a press release announcing the receipt of an audit... Rules. Nasdaq noted in its Notice, however, that if a company fails to include the audit opinion in its...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed Rule Change To...

  8. 75 FR 47651 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62605; File No. SR-NASDAQ-2010-068] Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change to Establish a Revenue Sharing Program With Correlix, Inc. July 30, 2010. On June 8, 2010, The NASDAQ Stock Market LLC (``NASDAQ'' or the ``Exchange'') filed wit...

  9. 75 FR 49543 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-13

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62663; File No. SR-NASDAQ-2010-077] Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change Relating to Pricing for Direct Circuit Connections August 9, 2010. On June 21, 2010, The NASDAQ Stock Market LLC (``NASDAQ'' or the ``Exchange'') filed with the...

  10. 77 FR 15826 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-16

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66576; File No. SR-NYSE-2012-01] Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving a Proposed Rule Change To Establish an NYBX Immediate-or- Cancel Order March 12, 2012. I. Introduction On January 11, 2012, the New York Stock Exchange LLC (``NYSE'' or ``Exchange'') file...

  11. 76 FR 71396 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Order Approving Proposed Rule Change, as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65729, File No. SR-BYX-2011-022] Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Order Approving Proposed Rule Change, as Modified by Partial Amendment No. 1, To Amend and Restate the Amended and Restated Bylaws of BATS Global Markets, Inc. November 10, 2011. I. Introduction On September 7...

  12. 77 FR 27254 - Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-09

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66911; File No. SR-ICEEU-2012-05] Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change To Amend the ICE Clear Europe Limited CDS Procedures, Finance Procedures, and Rules With Respect to the Calculation and Payment of Interest on Mark-To-Market Margin on...

  13. 75 FR 62443 - Self-Regulatory Organizations; NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-08

    ...-Regulatory Organizations; NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change To Adopt a..., Section 1 (Definitions) of the rules of the Nasdaq Options Market (``NOM'') to adopt a definition of... business days. This is similar to the process of other options exchanges that have adopted a Professional...

  14. 75 FR 38584 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Approving a Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  15. 75 FR 65541 - Self-Regulatory Organizations; Order Approving Proposed Rule Change by NASDAQ OMX PHLX, Inc. To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  16. 75 FR 25889 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-10

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62019; File No. SR-NYSEArca-2010-16] Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Approval of Proposed Rule Change Amending Rule 6.37A and Rule 6.64 April 30, 2010. On March 11, 2010, NYSE Arca, Inc. (``NYSE Arca'' or ``Exchange'') filed with the Securities and Exchange...

  17. 76 FR 32004 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-02

    ...-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule Change To Expand the Number of Components in the PHLX Gold/Silver Sector\\SM\\ Known as XAU\\SM\\, on Which Options Are Listed and... Act of 1934 (``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ a proposed rule change to expand the number of...

  18. 76 FR 78057 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-15

    ...\\ and Rule 19b-4 thereunder,\\2\\ a proposed rule change to introduce the Minimum Life Order as new order... proposes, by amending its rules to add Rule 3301(f)(11), to introduce the Minimum Life Order as a new order...-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule Change, as Modified...

  19. 77 FR 75239 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Approving a Proposed Rule Change, as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68430; File No. SR-NYSEArca-2012-111] Self-Regulatory Organizations; NYSE Arca, Inc.; Order Approving a Proposed Rule Change, as Modified by Amendment No. 1, To List and Trade Units of the Sprott Physical Platinum and Palladium Trust Pursuant to NYSE Arca Equities Rule 8.201 December 13, 2012. I...

  20. 77 FR 23300 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Order Approving a Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-18

    ...-Regulatory Organizations; BATS Y-Exchange, Inc.; Order Approving a Proposed Rule Change To Amend BATS Y-Exchange, Inc. Rule 2.12 to Make Permanent the Pilot Program That Permits BATS Y-Exchange, Inc. To Receive Inbound Routes of Equities Orders Through BATS Trading, Inc., BATS Y-Exchange's Routing Broker-Dealer...

  1. 75 FR 38585 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  2. Harmonization of reimbursement and regulatory approval processes: a systematic review of international experiences.

    PubMed

    Tsoi, Bernice; Masucci, Lisa; Campbell, Kaitryn; Drummond, Michael; O'Reilly, Daria; Goeree, Ron

    2013-08-01

    A considerable degree of overlap exists between reimbursement and regulatory approval of health technologies, and harmonization of certain aspects is both possible and feasible. Various models to harmonization have been suggested in which a number of practical attempts have been drawn from. Based on a review of the literature, approaches can be categorized into those focused on reducing uncertainty and developing economies of scale in the evidentiary requirements; and/or aligning timeframes and logistical aspects of the review process. These strategies can further be classified based on the expected level of structural and organizational change required to implement them into the existing processes. Passive processes require less modification, whereas active processes are associated with greater restructuring. Attempts so far at harmonization have raised numerous legal and practical issues and these must be considered when introducing a more harmonized framework into the existing regulatory and reimbursement arrangements.

  3. Prospective Activities outlined for Regulatory Approval in Ghana Overview

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abrefah, R.G.; Odoi, H.C.; Mo, S.C.

    The Ghana Research Reactor-1 (GHARR-1) is one of Chinese’s Miniature Neutron Source Reactor (MNSR) which was purchased under a tripartite agreement between Ghana, China and the IAEA. The reactor was installed in 1994 and has since been in operation without any incident. It has been used chiefly for Neutron Activation Analysis (NAA) and Training of students in the field of Nuclear Engineering. The GHARR-1 has been earmarked for the Conversion of Core from HEU to LEU which is in accordance with the GTRI program and other related and/or associated programs. Over the past few years the National Nuclear Research Institutemore » (NNRI), the Operating Organization of the Research Reactor for the Ghana Atomic Energy Commission (GAEC), has undertaken various tasks in order to implement the replacement of the reactor core. After completion, of the neutronic calculations, results showed that that an LEU fuel of 12.5% enrichment was desirable. However, recent developments have shown that an LEU fuel with 13% enrichment will be fabricated by the manufacturers, which is captured in a fuel specification document sent to NNRI by the CIAE. It is therefore imperative that all neutronic and thermal hydraulic calculation be done again to help acquire regulatory approval. Furthermore, the radiation exposure to personnel involved in the conversion must be estimated to help convince our regulators. This paper outlines the processes and activities that will enable us meet regulatory requirements.« less

  4. [Requirements for drug approval and additional benefits assessment: Regulatory aspects and experiences].

    PubMed

    Broich, K; Löbker, W; Schulte, A; Beinlich, P; Müller, T

    2016-04-01

    The early assessment of benefits of newly approved drugs with novel active substances or new applications, which came into force on 1 January 2011 still represents a challenge to all parties involved. This article highlights the definitions, regulatory requirements and interaction between drug marketing approval and early assessment of benefits in Germany. The constellation of an extensively harmonized European and even international drug authorization process with a predominantly national regulation of drug reimbursement situation inevitably causes friction, which could be markedly reduced through early joint advisory discussions during the planning phase for pivotal clinical trials. During the year 2015 the Federal Institute for Drugs and Medical Devices (BfArM) carried out 300 scientific advice procedures of which 34 were concerned with applications in the field of indications for the central nervous system (CNS). In comparison 98 advisory meetings were held by the Federal Joint Committee (G-BA) of which the BfArM provided advice in 12 instances and in 2 cases on CNS indications. Study design, endpoints and appropriate comparative therapies are the key issues in exchanges and discussions between the BfArM, the G‑BA and applicants. Under these aspects the BfArM and G‑BA promote an early and consistent involvement in early advice procedures regarding the prerequisites for drug approval and assessment of additional benefits.

  5. 77 FR 22032 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Granting Approval of a Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ...-Regulatory Organizations; New York Stock Exchange LLC; Order Granting Approval of a Proposed Rule Change... proposed rule change to amend NYSE Rule 476A to update its ``List of Exchange Rule Violations and Fines Applicable Thereto Pursuant to Rule 476A.'' The proposed rule change was published for comment in the Federal...

  6. 75 FR 65044 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval to a Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-21

    ... market value of publicly held shares for common stock on the Capital Market range from $5 million to $15...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval to a Proposed Rule Change To Modify the Eligibility Criteria for the Second Compliance Period for a Bid Price Deficiency on the Nasdaq...

  7. 76 FR 9065 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Approving a Proposed Rule Change To List...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-16

    ...-Regulatory Organizations; NYSE Arca, Inc.; Order Approving a Proposed Rule Change To List and Trade Shares of...,\\2\\ a proposed rule change to list and trade shares (``Shares'') of the SPDR Nuveen S&P High Yield... shares (``Shares'') under NYSE Arca Equities Rule 5.2(j)(3), Commentary .02, which governs the listing...

  8. 77 FR 23532 - Self-Regulatory Organizations; NYSE Amex LLC; Order Granting Approval of a Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-19

    ...-Regulatory Organizations; NYSE Amex LLC; Order Granting Approval of a Proposed Rule Change Amending NYSE Amex... Securities Exchange Act of 1934 (``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ a proposed rule change to amend....'' The proposed rule change was published for comment in the Federal Register on March 5, 2012.\\3\\ The...

  9. Determinants of Pregnant Women’s Online Self-Regulatory Activities for Appropriate Gestational Weight Gain

    PubMed Central

    Kim, Hye Kyung; Niederdeppe, Jeff; Guillory, Jamie; Graham, Meredith; Olson, Christine; Gay, Geri

    2015-01-01

    This study examined psychosocial and socio-demographic factors associated with pregnant women’s use of web-based tools to set and monitor personal goals for healthy diet and physical activity. These tools were made available to women participating in a randomized trial testing a web-based intervention to promote appropriate gestational weight gain. We used data from a baseline survey of pregnant women assigned to the intervention group and log data on women’s use of various intervention features (N = 873). Women who believed that appropriate gestational weight gain would lead to healthy outcomes for their child were more likely to engage in online goal-setting and self-monitoring. Less positive outcome expectancy beliefs about the relationship between their own weight and baby’s health partially explains why some at risk subpopulations (e.g., African-American women) were less likely to utilize online self-regulatory tools. This study specifies key psychosocial and motivational factors that guide the construction and monitoring of goals among pregnant women. These findings offer guidance for the design of interventions to promote self-regulatory techniques by identifying groups for whom those features are most likely to be useful, as well as psychological determinants of their use. PMID:25205417

  10. 76 FR 5630 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Approving a Proposed Rule Change, as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-01

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63777; File No. SR-Phlx-2010-157] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Approving a Proposed Rule Change, as Modified by Amendment Nos. 1 and 2, Relating to Complex Orders January 26, 2011. I. Introduction On November 29, 2010, NASDAQ OMX PHLX LLC (``Phlx'' or the ``Exchange'...

  11. 46 CFR 11.302 - Course approval.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 1 2013-10-01 2013-10-01 false Course approval. 11.302 Section 11.302 Shipping COAST... ENDORSEMENTS Training Schools with Approved Courses § 11.302 Course approval. (a) The Coast Guard approves courses satisfying regulatory requirements and those that substitute for a Coast Guard examination or a...

  12. 46 CFR 11.302 - Course approval.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Course approval. 11.302 Section 11.302 Shipping COAST... ENDORSEMENTS Training Schools with Approved Courses § 11.302 Course approval. (a) The Coast Guard approves courses satisfying regulatory requirements and those that substitute for a Coast Guard examination or a...

  13. 46 CFR 11.302 - Course approval.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Course approval. 11.302 Section 11.302 Shipping COAST... ENDORSEMENTS Training Schools with Approved Courses § 11.302 Course approval. (a) The Coast Guard approves courses satisfying regulatory requirements and those that substitute for a Coast Guard examination or a...

  14. 46 CFR 11.302 - Course approval.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Course approval. 11.302 Section 11.302 Shipping COAST... ENDORSEMENTS Training Schools with Approved Courses § 11.302 Course approval. (a) The Coast Guard approves courses satisfying regulatory requirements and those that substitute for a Coast Guard examination or a...

  15. 75 FR 7532 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-19

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... is hereby given that on February 4, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA...) (SEC Approves Consolidated FINRA Rules Governing Financial Responsibility). FINRA announced in...

  16. 77 FR 43620 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-25

    ... self-regulatory organization consents, the Commission shall either approve the proposed rule change...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer Period for Commission Action on Proposed Rule Change Relating to the Handling of Stop and Stop Limit...

  17. Ten years of marketing approvals of anticancer drugs in Europe: regulatory policy and guidance documents need to find a balance between different pressures

    PubMed Central

    Apolone, G; Joppi, R; Bertele', V; Garattini, S

    2005-01-01

    Despite important progress in understanding the molecular factors underlying the development of cancer and the improvement in response rates with new drugs, long-term survival is still disappointing for most common solid tumours. This might be because very little of the modest gain for patients is the result of the new compounds discovered and marketed recently. An assessment of the regulatory agencies' performance may suggest improvements. The present analysis summarizes and evaluates the type of studies and end points used by the EMEA to approve new anticancer drugs, and discusses the application of current regulations. This report is based on the information available on the EMEA web site. We identified current regulatory requirements for anticancer drugs promulgated by the agency and retrieved them in the relevant directory; information about empirical evidence supporting the approval of drugs for solid cancers through the centralised procedure were retrieved from the European Public Assessment Report (EPAR). We surveyed documents for drug applications and later extensions from January 1995, when EMEA was set up, to December 2004. We identified 14 anticancer drugs for 27 different indications (14 new applications and 13 extensions). Overall, 48 clinical studies were used as the basis for approval; randomised comparative (clinical) trial (RCT) and Response Rate were the study design and end points most frequently adopted (respectively, 25 out of 48 and 30 out of 48). In 13 cases, the EPAR explicitly reported differences between arms in terms of survival: the range was 0–3.7 months, and the mean and median differences were 1.5 and 1.2 months. The majority of studies (13 out of 27, 48%) involved the evaluation of complete and/or partial tumour responses, with regard to the end points supporting the 27 indications. Despite the recommendations of the current EMEA guidance documents, new anticancer agents are still often approved on the basis of small single arm

  18. Ten years of marketing approvals of anticancer drugs in Europe: regulatory policy and guidance documents need to find a balance between different pressures.

    PubMed

    Apolone, G; Joppi, R; Bertele', V; Garattini, S

    2005-09-05

    Despite important progress in understanding the molecular factors underlying the development of cancer and the improvement in response rates with new drugs, long-term survival is still disappointing for most common solid tumours. This might be because very little of the modest gain for patients is the result of the new compounds discovered and marketed recently. An assessment of the regulatory agencies' performance may suggest improvements. The present analysis summarizes and evaluates the type of studies and end points used by the EMEA to approve new anticancer drugs, and discusses the application of current regulations. This report is based on the information available on the EMEA web site. We identified current regulatory requirements for anticancer drugs promulgated by the agency and retrieved them in the relevant directory; information about empirical evidence supporting the approval of drugs for solid cancers through the centralised procedure were retrieved from the European Public Assessment Report (EPAR). We surveyed documents for drug applications and later extensions from January 1995, when EMEA was set up, to December 2004. We identified 14 anticancer drugs for 27 different indications (14 new applications and 13 extensions). Overall, 48 clinical studies were used as the basis for approval; randomised comparative (clinical) trial (RCT) and Response Rate were the study design and end points most frequently adopted (respectively, 25 out of 48 and 30 out of 48). In 13 cases, the EPAR explicitly reported differences between arms in terms of survival: the range was 0-3.7 months, and the mean and median differences were 1.5 and 1.2 months. The majority of studies (13 out of 27, 48%) involved the evaluation of complete and/or partial tumour responses, with regard to the end points supporting the 27 indications. Despite the recommendations of the current EMEA guidance documents, new anticancer agents are still often approved on the basis of small single arm

  19. 10 CFR 55.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Information collection requirements: OMB approval. 55.8 Section 55.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) OPERATORS' LICENSES General Provisions § 55.8 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission has...

  20. 10 CFR 55.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 55.8 Section 55.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) OPERATORS' LICENSES General Provisions § 55.8 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission has...

  1. Recent drug approvals from the US FDA and EMEA: what the future holds.

    PubMed

    Pevarello, Paolo

    2009-04-01

    The decreased productivity of the pharmaceutical industry in terms of new medical entities approved by the US FDA and the European Medicines Agency (EMEA) on a yearly basis has long been debated. This review will analyze overall new drug applications (NDAs) approved by both the FDA and EMEA in 2007, with the aim of finding trends (also looking at the past) that can be used to predict what the future may be. After a general introduction to the regulatory terminology, NDA approvals in 2007 are divided into categories (new applications of old medicines, metabolites, enantiomers and prodrugs, biological products, natural products and small organic molecule new molecular entities) and discussed. General aspects of the NDA approvals, such as historical trends, the length of the drug-discovery process, geography, differences among therapeutic areas, and the relative role of biotech and pharma industries are also outlined. From this analysis, a perspective is gained on some aspects that will probably influence future drug approvals. The conclusion is that 2007 may represent an inflexion point, in terms of quality if not quantity of new approvals, and that the future may be brighter than previously forecast.

  2. 10 CFR 40.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 40.8 Section 40.8 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL General Provisions § 40.8 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission has...

  3. 10 CFR 100.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Information collection requirements: OMB approval. 100.8 Section 100.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) REACTOR SITE CRITERIA § 100.8 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission has submitted the information...

  4. 10 CFR 100.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 100.8 Section 100.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) REACTOR SITE CRITERIA § 100.8 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission has submitted the information...

  5. 10 CFR 9.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Information collection requirements: OMB approval. 9.8 Section 9.8 Energy NUCLEAR REGULATORY COMMISSION PUBLIC RECORDS § 9.8 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission has submitted the information collection...

  6. 10 CFR 9.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Information collection requirements: OMB approval. 9.8 Section 9.8 Energy NUCLEAR REGULATORY COMMISSION PUBLIC RECORDS § 9.8 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission has submitted the information collection...

  7. 10 CFR 100.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Information collection requirements: OMB approval. 100.8 Section 100.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) REACTOR SITE CRITERIA § 100.8 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission has submitted the information...

  8. 10 CFR 9.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Information collection requirements: OMB approval. 9.8 Section 9.8 Energy NUCLEAR REGULATORY COMMISSION PUBLIC RECORDS § 9.8 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission has submitted the information collection...

  9. 10 CFR 20.1009 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Information collection requirements: OMB approval. 20.1009 Section 20.1009 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION General Provisions § 20.1009 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission...

  10. 10 CFR 20.1009 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 20.1009 Section 20.1009 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION General Provisions § 20.1009 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission...

  11. 10 CFR 20.1009 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Information collection requirements: OMB approval. 20.1009 Section 20.1009 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION General Provisions § 20.1009 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission...

  12. 10 CFR 20.1009 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Information collection requirements: OMB approval. 20.1009 Section 20.1009 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION General Provisions § 20.1009 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission...

  13. 10 CFR 20.1009 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Information collection requirements: OMB approval. 20.1009 Section 20.1009 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION General Provisions § 20.1009 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission...

  14. 10 CFR 9.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 9.8 Section 9.8 Energy NUCLEAR REGULATORY COMMISSION PUBLIC RECORDS § 9.8 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission has submitted the information collection...

  15. 10 CFR 9.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Information collection requirements: OMB approval. 9.8 Section 9.8 Energy NUCLEAR REGULATORY COMMISSION PUBLIC RECORDS § 9.8 Information collection requirements: OMB approval. (a) The Nuclear Regulatory Commission has submitted the information collection...

  16. 76 FR 43360 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-20

    .... The text of the proposed rule change is set forth below. Proposed new language is italicized; proposed... methodology approved by FINRA as announced in a Regulatory Notice (``approved margin methodology''). The... an Approved Margin Methodology. Members shall require as a minimum for computing customer or broker...

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

    PubMed Central

    Klein, Gregory; Carr, Lauren; Kessler, Larry; Sullivan, Sean D.

    2012-01-01

    Abstract 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. PMID:22275726

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

    PubMed

    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.

  19. 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.

    PubMed

    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.

  20. 78 FR 12405 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate...\\ 17 CFR 240.19b-4(f)(6). I. Self-Regulatory Organization's Statement of the Terms of Substance of the... Approval of Change in Ownership, Control, or Business Operations) to provide for a refund of the...

  1. Innovation under Regulatory Uncertainty: Evidence from Medical Technology

    PubMed Central

    Stern, Ariel Dora

    2016-01-01

    This paper explores how the regulatory approval process affects innovation incentives in medical technologies. Prior studies have found early mover regulatory advantages for drugs. I find the opposite for medical devices, where pioneer entrants spend 34 percent (7.2 months) longer than follow-on entrants in regulatory approval. Back-of-the- envelope calculations suggest that the cost of a delay of this length is upwards of 7 percent of the total cost of bringing a new high-risk device to market. Considering potential explanations, I find that approval times are largely unrelated to technological novelty, but are meaningfully reduced by the publication of objective regulatory guidelines. Finally, I consider how the regulatory process affects small firms’ market entry patterns and find that small firms are less likely to be pioneers in new device markets, a fact consistent with relatively higher costs of doing so for more financially constrained firms. PMID:28652646

  2. Regulatory Challenges for Cartilage Repair Technologies.

    PubMed

    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.

  3. Regulatory Challenges for Cartilage Repair Technologies

    PubMed Central

    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. PMID:26069647

  4. A rational regulatory approach for positron emission tomography imaging probes: from "first in man" to NDA approval and reimbursement.

    PubMed

    Barrio, Jorge R; Marcus, Carol S; Hung, Joseph C; Keppler, Jennifer S

    2004-01-01

    We propose a new regulatory approach for positron emission tomography (PET) molecular imaging probes, essential tools in today's medicine. Even though the focus of this paper is on positron-emitting labeled probes, it is also justified to extend this proposed regulatory approach to other diagnostic nuclear medicine radiopharmaceuticals. Key aspects of this proposal include: (1) PET molecular imaging probes would be placed in a "no significant risk" category, similar to that category for devices in current Food and Drug Administration (FDA) regulations, based on overwhelming scientific evidence that demonstrates their faultless safety profile; (2) the FDA-sanctioned Radioactive Drug Research Committee (RDRC) will oversee all diagnostic research with these probes. The newly defined RDRC should approve "first in man" use; supervise a broader spectrum of diagnostic research protocols, including those looking to demonstrate initial efficacy, as well as multicenter clinical trials and the use of molecular imaging probes as a screening tool in drug discovery. The current investigational new drug (IND) mechanism is thus eliminated for these diagnostic probes; (3) when a molecular imaging probe has demonstrated diagnostic efficacy, FDA approval (i.e., NDA) will be sought. The review will be done by a newly constituted Radioactive Drug Advisory Committee (RDAC) composed of experts chosen by the professional societies, who would provide a binding assessment of the adequacy of the safety and efficacy data. When the RDAC recommends its diagnostic use on scientific and medical grounds, the molecular imaging probe becomes FDA approved. After a molecular imaging probe is approved for a diagnostic indication, the existing mechanism to seek reimbursement will be utilized; and (4) the FDA would retain its direct oversight function for traditional manufacturers engaged in commercial distribution of the approved diagnostic molecular imaging probes (i.e., under NDA) to monitor

  5. 77 FR 32703 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-01

    ... organization consents, the Commission shall either approve the proposed rule change, disapprove the proposed...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer Period for Commission Action on Proposed Rule Change Relating to Post-Trade Transparency for Agency Pass...

  6. 78 FR 74012 - Approval and Promulgation of Implementation Plans; State of Oregon; Revised Format for Materials...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-10

    ...-regulatory and quasi-regulatory portions of the Oregon SIP. DATES: This action is effective January 9, 2014.... EPA-approved source-specific permits. 5. EPA-approved nonregulatory and quasi-regulatory provisions...

  7. 48 CFR 2022.103-4 - Approvals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Approvals. 2022.103-4 Section 2022.103-4 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION SOCIOECONOMIC PROGRAMS APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Basic Labor Policies 2022.103-4 Approvals...

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

    PubMed

    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

  9. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13.

    PubMed

    Davis, Courtney; Naci, Huseyin; Gurpinar, Evrim; Poplavska, Elita; Pinto, Ashlyn; Aggarwal, Ajay

    2017-10-04

    Objective  To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design  Retrospective cohort study. Setting  Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013. Main outcome measures  Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results  From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years' follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%). Conclusions

  10. New antirheumatic drugs: any real added value? A critical overview of regulatory criteria for their marketing approval.

    PubMed

    Bertele', Vittorio; Assisi, Alessandro; Di Muzio, Valeria; Renzo, Danila; Garattini, Silvio

    2007-09-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disorder causing chronic polyarticular synovial inflammation and progressive joint damage. New anti-rheumatic drugs, such as leflunomide, infliximab, etanercept, adalimumab and anakinra, have recently become available. The aim of this paper is to summarize and critically evaluate the type of studies and clinical endpoints accepted by the European Medicines Agency (EMEA) to approve these new drugs. Information regarding the approval of antirheumatic drugs was obtained from European Public Assessment Reports (EPARs) and published pivotal studies. Leflunomide is the only non-biological disease-modifying anti-rheumatic drug (DMARD) to receive recent approval for RA treatment, but strong evidence of its superiority over conventional therapies is lacking. Anakinra in combination with methotrexate received approval as a DMARD for RA on the basis of two pivotal trials in which American College of Rheumatology response criteria (ACR 20 response) were used as the sole primary endpoint. For easier demonstration of efficacy, studies leading to first approval of etanercept, infliximab and adalimumab were carried out on non-responders to DMARDs. Once on the market, these drugs gained an extension of the indication to methotrexate-naïve patients. Studies that provided the basis for approval were not adequately designed, given the lack of an active control and the choice of ACR response as the only clinical endpoint. Consequently, only a weak proof of efficacy emerged for the treatment of signs and symptoms of RA, and these drugs failed to show real benefit in slowing radiographic progression. Serious infections, changes in blood cell counts, severe skin and hepatic infections were the main adverse events that emerged from the clinical studies. Therefore, the unconvincing benefit of the new antirheumatic drugs can scarcely outweigh the risk associated with their use. Moreover, the monthly costs in Italy of the new biological

  11. 78 FR 52219 - State of Georgia Relinquishment of Sealed Source and Device Evaluation and Approval Authority

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-22

    ... NUCLEAR REGULATORY COMMISSION [NRC-2013-0196] State of Georgia Relinquishment of Sealed Source and... evaluate and approve sealed source and device (SS&D) applications in the State of Georgia and approved the... regulatory authority for evaluating and approving sealed source and device applications on August 20, 2013...

  12. [Clinical trials of vnorelbine in breast cancer--its scientific usefulness and development history until regulatory approval].

    PubMed

    Tominaga, Takeshi

    2006-04-01

    Vinorelbine, a novel vinca alkaloid derivative developed in France, has been widely used for the treatment of breast cancer and non-small cell lung cancer since the 1990s in many foreign countries. In Japan, it has been available for the treatment of non-small cell lung cancer since 1999, and the additional indication of breast cancer was approved in May 2005. Japanese phase I clinical trials started in 1988. A total of six trials have been conducted in patients with advanced or recurrent breast cancer, and have provided evidence of efficacy in all groups of patients, including those receiving vinorelbine as first-line monotherapy and those previously treated with both anthracyclines and taxanes. This report reviews the data from these studies and also presents the results of combination therapy evaluated outside Japan. In addition,we explain why it took 17 years for vinorelbine to be approved despite the fact that as early as the beginning of development, it was scientifically proven to be very useful in patients with breast cancer, and that the new drug application was submitted in 1993. The relationship between healthcare professionals, patients and the regulatory agency is also discussed to point out related issues.

  13. 10 CFR 72.234 - Conditions of approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Conditions of approval. 72.234 Section 72.234 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR THE INDEPENDENT STORAGE OF SPENT... Spent Fuel Storage Casks § 72.234 Conditions of approval. (a) The certificate holder and applicant for a...

  14. 78 FR 9807 - Utah Regulatory Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... DEPARTMENT OF THE INTERIOR Office of Surface Mining Reclamation and Enforcement 30 CFR Part 944... Mining Reclamation and Enforcement, Interior. ACTION: Final rule; approval of amendment. SUMMARY: We are approving an amendment to the Utah regulatory program (the ``Utah program'') under the Surface Mining...

  15. 7 CFR 1735.90 - Preliminary approvals.

    Code of Federal Regulations, 2010 CFR

    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...

  16. 10 CFR 60.8 - Information collection requirements: Approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Information collection requirements: Approval. 60.8 Section 60.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES General Provisions § 60.8 Information collection requirements: Approval. (a) The...

  17. 10 CFR 52.11 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... A, B, C, D, and N of part 52. ... 10 Energy 2 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 52.11 Section 52.11 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR...

  18. 10 CFR 52.11 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... A, B, C, D, and N of part 52. ... 10 Energy 2 2012-01-01 2012-01-01 false Information collection requirements: OMB approval. 52.11 Section 52.11 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR...

  19. Accelerating drug development and approval.

    PubMed

    Cole, Patrick

    2010-01-01

    Regulatory agencies are the gateway between the pharma/biotech industry and patients and can serve as stimulators of new drug development. This article highlights several means of doing so implemented thus far, many with already impressive histories, such as orphan drug legislation, and others of a more experimental nature, such as the FDA's priority review voucher program. These initiatives represent different approaches to finding treatments for rare and widespread but neglected diseases, as well as speeding the development process for pharmaceutical and biological agents more generally. Commercial incentives, streamlined regulatory processing, exploratory trial designs, research assistance and cash infusions are all means of promoting drug development being explored in the United States, Europe and beyond. In some cases, such as fast track designation and priority review vouchers, regulatory agencies have turned their own processes into incentives, offering advantageous alternative routes to product approval, like a faster lane on the highway for vehicles carrying multiple passengers. In 2009, regulatory agencies and the governments they represent also had to confront two tremendous challenges: the global recession and the H1N1 influenza virus pandemic. These tests have been met with increased funding in the former case and coordinated efforts to develop, approve and stockpile H1N1 vaccines in the latter.

  20. FDA approval of cardiac implantable electronic devices via original and supplement premarket approval pathways, 1979-2012.

    PubMed

    Rome, Benjamin N; Kramer, Daniel B; Kesselheim, Aaron S

    The US Food and Drug Administration (FDA) evaluates high-risk medical devices such as cardiac implantable electronic devices (CIEDs), including pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, via the premarket approval (PMA) process, during which manufacturers submit clinical data demonstrating safety and effectiveness. Subsequent changes to approved high-risk devices are implemented via "supplements," which may not require additional clinical testing. To characterize the prevalence and characteristics of changes to CIEDs made through the PMA supplement process. Using the FDA's PMA database, we reviewed all CIEDs approved as original PMAs or supplements from 1979 through 2012. For each supplement, we collected the date approved, type of supplement (panel-track, 180-day, real-time, special, and 30-day notice), and the nature of the changes. We calculated the number of supplements approved per PMA and analyzed trends relating to different supplement regulatory categories over time. For supplements approved via the 180-day regulatory pathway, which often involve significant design changes, from 2010-2012, we identified how often additional clinical data were collected. From 1979-2012, the FDA approved 77 original and 5829 supplement PMA applications for CIEDs, with a median of 50 supplements per original PMA (interquartile range [IQR], 23-87). Excluding manufacturing changes that do not alter device design, the number of supplements approved each year was stable around a mean (SD) of 2.6 (0.9) supplements per PMA per year. Premarket approvals remained active via successive supplements over a median period of 15 years (IQR, 8-20), and 79% of the 77 original PMAs approved during our study period were the subject of at least 1 supplement in 2012. Thirty-seven percent of approved supplements involved a change to the device's design. Among 180-day supplements approved from 2010-2012, 23% (15/64) included new clinical data

  1. 78 FR 41311 - Approval of Air Quality Implementation Plans; Indiana; Approval of “Infrastructure” SIP With...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-10

    ... Elements Required Under Sections 110(a)(1) and (2) for the 2006 24-Hour Fine Particle (PM 2.5 ) National... Indiana Nonregulatory and Quasi-Regulatory Provisions Title Indiana date EPA approval Explanation...

  2. 10 CFR 51.17 - Information collection requirements; OMB approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Information collection requirements; OMB approval. 51.17 Section 51.17 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) ENVIRONMENTAL PROTECTION REGULATIONS FOR DOMESTIC LICENSING AND RELATED REGULATORY FUNCTIONS National Environmental Policy Act-Regulations...

  3. 10 CFR 51.17 - Information collection requirements; OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Information collection requirements; OMB approval. 51.17 Section 51.17 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) ENVIRONMENTAL PROTECTION REGULATIONS FOR DOMESTIC LICENSING AND RELATED REGULATORY FUNCTIONS National Environmental Policy Act-Regulations...

  4. 75 FR 33678 - List of Approved Spent Fuel Storage Casks: MAGNASTOR System, Revision 1

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-15

    ... of establishing one or more technologies that the [Nuclear Regulatory] Commission may, by rule... technology approved by the Commission under Section 218(a) for use at the site of any civilian nuclear power... NUCLEAR REGULATORY COMMISSION 10 CFR Part 72 [NRC-2010-0140] RIN 3150-AI86 List of Approved Spent...

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

    PubMed

    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.

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

    PubMed

    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.

  7. 10 CFR 26.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 26.8 Section 26.8 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Administrative Provisions § 26.8 Information collection requirements: OMB approval. (a) The NRC has submitted the information...

  8. 10 CFR 26.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Information collection requirements: OMB approval. 26.8 Section 26.8 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Administrative Provisions § 26.8 Information collection requirements: OMB approval. (a) The NRC has submitted the information...

  9. 10 CFR 19.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Section 19.8 Energy NUCLEAR REGULATORY COMMISSION NOTICES, INSTRUCTIONS AND REPORTS TO WORKERS: INSPECTION... collection of information unless it displays a currently valid OMB control number. OMB has approved the information collection requirements contained in this part under control number 3150-0044. (b) The approved...

  10. 10 CFR 15.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 15.8 Section 15.8 Energy NUCLEAR REGULATORY COMMISSION DEBT COLLECTION PROCEDURES Application and Coverage § 15.8 Information collection requirements: OMB approval. This part contains no information collection...

  11. 10 CFR 26.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Information collection requirements: OMB approval. 26.8 Section 26.8 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Administrative Provisions § 26.8 Information collection requirements: OMB approval. (a) The NRC has submitted the information...

  12. 10 CFR 26.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Information collection requirements: OMB approval. 26.8 Section 26.8 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Administrative Provisions § 26.8 Information collection requirements: OMB approval. (a) The NRC has submitted the information...

  13. 10 CFR 26.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Information collection requirements: OMB approval. 26.8 Section 26.8 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Administrative Provisions § 26.8 Information collection requirements: OMB approval. (a) The NRC has submitted the information...

  14. 10 CFR 75.9 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 75.9 Section 75.9 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) SAFEGUARDS ON NUCLEAR MATERIAL-IMPLEMENTATION OF US/IAEA AGREEMENT General Provisions § 75.9 Information collection requirements: OMB approval...

  15. 10 CFR 75.9 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Information collection requirements: OMB approval. 75.9 Section 75.9 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) SAFEGUARDS ON NUCLEAR MATERIAL-IMPLEMENTATION OF US/IAEA AGREEMENT General Provisions § 75.9 Information collection requirements: OMB approval...

  16. 10 CFR 32.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 32.8 Section 32.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER...) The Nuclear Regulatory Commission has submitted the information collection requirements contained in...

  17. 10 CFR 32.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Information collection requirements: OMB approval. 32.8 Section 32.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER...) The Nuclear Regulatory Commission has submitted the information collection requirements contained in...

  18. 78 FR 37848 - ASME Code Cases Not Approved for Use

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ...The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment draft regulatory guide (DG), DG-1233, ``ASME Code Cases not Approved for Use.'' This regulatory guide lists the American Society of Mechanical Engineers (ASME) Code Cases that the NRC has determined not to be acceptable for use on a generic basis.

  19. A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part III. Countermeasures under early stages of development along with 'standard of care' medicinal and procedures not requiring regulatory approval for use.

    PubMed

    Singh, Vijay K; Hanlon, Briana K; Santiago, Paola T; Seed, Thomas M

    2017-09-01

    Terrorist attacks, with their intent to maximize psychological and economic damage as well as inflicting sickness and death on given targeted populations, are an ever-growing worldwide concern in government and public sectors as they become more frequent, violent, and sensational. If given the chance, it is likely that terrorists will use radiological or nuclear weapons. To thwart these sinister efforts, both physical and medical countermeasures against these weapons are currently being researched and developed so that they can be utilized by the first responders, military, and medical providers alike. This is the third article of a three-part series in which we have reviewed additional radiation countermeasures that are currently under early preclinical phases of development using largely animal models and have listed and discussed clinical support measures, including agents used for radiation-induced emesis, as well as countermeasures not requiring Food and Drug Administration approval. Despite the significant progress that has been made in this area during the last several years, additional effort is needed in order to push promising new agents, currently under development, through the regulatory pipeline. This pipeline for new promising drugs appears to be unreasonably slow and cumbersome; possible reasons for this inefficiency are briefly discussed. Significant and continued effort needs to be afforded to this research and development area, as to date, there is no approved radioprotector that can be administered prior to high dose radiation exposure. This represents a very significant, unmet medical need and a significant security issue. A large number of agents with potential to interact with different biological targets are under development. In the next few years, several additional radiation countermeasures will likely receive Food and Drug Administration approval, increasing treatment options for victims exposed to unwanted ionizing irradiation.

  20. Trial endpoints for drug approval in oncology: Chemoprevention.

    PubMed

    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.

  1. 10 CFR 61.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 2 2012-01-01 2012-01-01 false Information collection requirements: OMB approval. 61.8 Section 61.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.8 Information collection requirements: OMB approval. (a) The Nuclear...

  2. 10 CFR 61.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Information collection requirements: OMB approval. 61.8 Section 61.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.8 Information collection requirements: OMB approval. (a) The Nuclear...

  3. 10 CFR 61.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Information collection requirements: OMB approval. 61.8 Section 61.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.8 Information collection requirements: OMB approval. (a) The Nuclear...

  4. 10 CFR 61.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 61.8 Section 61.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.8 Information collection requirements: OMB approval. (a) The Nuclear...

  5. 10 CFR 61.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Information collection requirements: OMB approval. 61.8 Section 61.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.8 Information collection requirements: OMB approval. (a) The Nuclear...

  6. Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable.

    PubMed

    Fisher, Marc; Albers, Gregory W; Donnan, Geoffrey A; Furlan, Anthony J; Grotta, James C; Kidwell, Chelsea S; Sacco, Ralph L; Wechsler, Lawrence R

    2005-08-01

    Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval. The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed. The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies.

  7. 75 FR 24786 - List of Approved Spent Fuel Storage Casks: NUHOMS® HD System Revision 1

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-06

    ... of establishing one or more technologies that the [Nuclear Regulatory] Commission may, by rule... technology approved by the Commission under Section 218(a) for use at the site of any civilian nuclear power... NUCLEAR REGULATORY COMMISSION 10 CFR Part 72 RIN 3150-AI75 [NRC-2009-0538] List of Approved Spent...

  8. A decade of safety-related regulatory action in the Netherlands: a retrospective analysis of direct healthcare professional communications from 1999 to 2009.

    PubMed

    Mol, Peter G M; Straus, Sabine M J M; Piening, Sigrid; de Vries, Jonie T N; de Graeff, Pieter A; Haaijer-Ruskamp, Flora M

    2010-06-01

    As pre-approval trials are inherently limited in assessing the complete benefit-risk profile of a new drug, serious safety issues may emerge once a drug gains widespread use after approval. Regulators face the dilemma of balancing timely market access with the need for complete data on risks. This challenge has led to a life-cycle approach but, so far, few data are available on post-approval safety issues requiring regulatory action. The aim of this study is to determine the frequency, timing and nature of safety issues that necessitated safety-related regulatory action in the form of a Direct Healthcare Professional Communication (DHPC) issued by pharmaceutical companies in collaboration with the Dutch Medicines Evaluation Board during the past decade. All DHPCs issued in the Netherlands from 1 January 1999 to 1 January 2009 were retrospectively collected from the national regulatory authorities. Elapsed time between the approval date and the issue of the DHPC was determined. Characteristics of the action including the nature of the safety issue (according to Medical Dictionary for Regulatory Activities [MedDRA] terminology), type of drug and procedural aspects of the regulatory action taken were reviewed. DHPC characteristics were tabulated and explorative non-parametric tests were performed to study the effect of safety issue, drug class, drug type, orphan drug and first-in-class status on elapsed time from approval to the DHPC. 157 DHPCs were issued concerning 112 different active substances, approximately 9% (112/1200) of active substances available in the Netherlands in 2007. The number of DHPCs issued increased by 2.1 (95% CI 1.2, 3.1; p < 0.001) DHPCs per year over the past decade, reaching a total of 25 in 2008. The median time between approval and DHPC was 5.3 years (range 0.13-48 years). No significant trend in elapsed time to DHPC was observed in relation to the studied years (p = 0.06). One-third of all DHPCs were issued in the first 3 years after

  9. 10 CFR 170.8 - Information collection requirements: OMB approval

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Information collection requirements: OMB approval 170.8 Section 170.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FEES FOR FACILITIES, MATERIALS, IMPORT AND EXPORT LICENSES, AND OTHER REGULATORY SERVICES UNDER THE ATOMIC ENERGY ACT OF 1954, AS AMENDED General...

  10. 10 CFR 170.8 - Information collection requirements: OMB approval

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Information collection requirements: OMB approval 170.8 Section 170.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FEES FOR FACILITIES, MATERIALS, IMPORT AND EXPORT LICENSES, AND OTHER REGULATORY SERVICES UNDER THE ATOMIC ENERGY ACT OF 1954, AS AMENDED General...

  11. 10 CFR 170.8 - Information collection requirements: OMB approval

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 2 2012-01-01 2012-01-01 false Information collection requirements: OMB approval 170.8 Section 170.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FEES FOR FACILITIES, MATERIALS, IMPORT AND EXPORT LICENSES, AND OTHER REGULATORY SERVICES UNDER THE ATOMIC ENERGY ACT OF 1954, AS AMENDED General...

  12. 10 CFR 170.8 - Information collection requirements: OMB approval

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Information collection requirements: OMB approval 170.8 Section 170.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FEES FOR FACILITIES, MATERIALS, IMPORT AND EXPORT LICENSES, AND OTHER REGULATORY SERVICES UNDER THE ATOMIC ENERGY ACT OF 1954, AS AMENDED General...

  13. 10 CFR 170.8 - Information collection requirements: OMB approval

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Information collection requirements: OMB approval 170.8 Section 170.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FEES FOR FACILITIES, MATERIALS, IMPORT AND EXPORT LICENSES, AND OTHER REGULATORY SERVICES UNDER THE ATOMIC ENERGY ACT OF 1954, AS AMENDED General...

  14. An update on the clinical evidence that supports biosimilar approvals in Europe.

    PubMed

    Mielke, Johanna; Jilma, Bernd; Jones, Byron; Koenig, Franz

    2018-03-25

    Sponsors and regulators have more than 10 years of experience with the development of biosimilars in Europe. However, the regulatory pathway is still evolving. The present article provides an update on biosimilar development in practice by reviewing the clinical development programmes of recently approved biosimilars in Europe. We used the European public assessment reports (EPARs) which are published by the European Medicines Agency (EMA) for a comparison of the clinical development programmes of the 37 approved biosimilars in Europe. Here, we present novel strategies in the development of biosimilars by focusing specifically on the 17 biosimilars that have gained approval in the last year, but we also compare additional key characteristics for all approved biosimilars. The high variability of the clinical development strategies that we found previously was confirmed in the present analysis. Compared with earlier biosimilar applications, more nonstandard development strategies have been used recently. This includes, for example, applications without any studies in patients, and more complex study designs. During this study, we found that the EPARs for biosimilars seem to be improving; however, we identified important details which were still often missing. We provide a proposal for a checklist of the minimum information that should be included in biosimilar EPARs for giving the general public insights into the rationale for the approval of biosimilars. European regulators still seem to be open to consider approaches that differ from the guidelines or previous applications, as long as justification is provided. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  15. 77 FR 4461 - New Mexico Regulatory Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-30

    ... [SATS No. NM-048-FOR; Docket ID OSM-2010-0014] New Mexico Regulatory Program AGENCY: Office of Surface... approving an amendment to the New Mexico regulatory program (the ``New Mexico program'') under the Surface Mining Control and Reclamation Act of 1977 (``SMCRA'' or ``the Act''). New Mexico proposed non...

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

    PubMed Central

    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

  17. Biosimilars approval process.

    PubMed

    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.

  18. Review of oncology and hematology drug product approvals at the US Food and Drug Administration between July 2005 and December 2007.

    PubMed

    Sridhara, Rajeshwari; Johnson, John R; Justice, Robert; Keegan, Patricia; Chakravarty, Aloka; Pazdur, Richard

    2010-02-24

    The Office of Oncology Drug Products (OODP) in the Center for Drug Evaluation and Research at the US Food and Drug Administration began reviewing marketing applications for oncological and hematologic indications in July 2005. We conducted an overview of products that were reviewed by the OODP for marketing approval and the regulatory actions taken during July 2005 to December 2007. We identified all applications that were reviewed by the OODP from July 1, 2005, through December 31, 2007, and reviewed the actions that OODP took. We also sought the basis for the actions taken, including the clinical trial design, endpoints used, patient accrual in the trial(s) supporting approval, and the type of regulatory approval. During the study period, the OODP reviewed marketing applications for 60 new indications and took regulatory action on 58 indications. Regulatory action was based on a risk-benefit evaluation of the data submitted with each application. Products that demonstrated efficacy and had an acceptable risk-benefit ratio were granted either regular or accelerated marketing approval for use in the specific indication that was studied. Regular approval was based on endpoints that demonstrated that the drug provided clinical benefit as evidenced by a longer or better life or a favorable effect on an established surrogate for a longer or better life. Accelerated approval was based on a less well-established surrogate endpoint that was reasonably likely to predict a longer or better life. Of the 53 new indications that were approved during the study period, 39 received regular approval, nine received accelerated approval, and five were converted from accelerated to regular approval. Five applications were not approved, and two applications were withdrawn before any regulatory action was taken. Eighteen of the 53 indications that were approved were for new molecular entities. During the study period, regulatory action was taken on 58 of the 60 marketing applications

  19. 30 CFR 906.10 - State regulatory program approval.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Natural Resources, Division of Minerals and Geology, Centennial Building, room 215, 1313 Sherman Street..., the Colorado Department of Natural Resources was deemed the regulatory authority in Colorado for...

  20. Canadian regulatory perspectives on genome engineered crops

    PubMed Central

    Smyth, Stuart J.

    2017-01-01

    ABSTRACT New breeding techniques in plant agriculture exploded upon the scene about two years ago, in 2014. While these innovative plant breeding techniques, soon to be led by CRISPR/Cas9, initially appear to hold tremendous promise for plant breeding, if not a revolution for the industry, the question of how the products of these technologies will be regulated is rapidly becoming a key aspect of the technology's future potential. Regulation of innovative technologies and products has always lagged that of the science, but in the past decade, regulatory systems in many jurisdictions have become gridlocked as they try to regulate genetically modified (GM) crops. This regulatory incapability to efficiently assess and approve innovative new agricultural products is particularly important for new plant breeding techniques as if these techniques are classified as genetically modified breeding techniques, then their acceptance and future will diminish considerably as they will be rejected by the European Union. Conversely, if the techniques are accepted as conventional plant breeding, then the future is blindingly bright. This article examines the international debate about the regulation of new plant breeding techniques and then assesses how the Canadian regulatory system has approached the regulation of these technologies through two more public product approvals, GM apples and GM potatoes, then discusses other crop variety approval and those in the regulatory pipeline. PMID:27858499

  1. 78 FR 15383 - Approval of Direct Transfer of Licenses and Issuance of License Amendment To Effectuate Such...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-11

    ... NUCLEAR REGULATORY COMMISSION [Docket Nos. 70-7003 and 70-7004; NRC-2010-0355] Approval of Direct... Operating, LLC AGENCY: Nuclear Regulatory Commission. ACTION: Notice of approval of direct transfer of control and issuance of license amendments to effectuate such transfers. SUMMARY: The U.S. Nuclear...

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

    PubMed Central

    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. PMID:29184849

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

    PubMed

    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.

  4. 30 CFR 935.10 - State regulatory program approval.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...: (a) Ohio Department of Natural Resources, Division of Reclamation, Building H-2, 1855 Fountain Square..., the Department of Natural Resources shall be deemed the regulatory authority in Ohio for all surface...

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

    PubMed

    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.

  6. 30 CFR 938.15 - Approval of Pennsylvania regulatory program amendments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Subsidence and Land 2001 Conservation Act: Repeal of Section 4 (52 P.S. 1406.4); 5(b)(partial approval); 5.1...)); 5.2(a)(1), (2), and (3) (52 P.S. 1406.5b(a)(1), (2), and (3)); 5.2(b)(1) (52 P.S. 1406.5b(b)(1)); 5... approval); 5.4(a)(1), (2) and (4) (52 P.S. 1406.5d(a)(1), (2) and (4)); 5.4(b) (52 P.S. 1406.5d(b)); 5.5(a...

  7. 30 CFR 938.15 - Approval of Pennsylvania regulatory program amendments.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Subsidence and Land 2001 Conservation Act: Repeal of Section 4 (52 P.S. 1406.4); 5(b)(partial approval); 5.1...)); 5.2(a)(1), (2), and (3) (52 P.S. 1406.5b(a)(1), (2), and (3)); 5.2(b)(1) (52 P.S. 1406.5b(b)(1)); 5... approval); 5.4(a)(1), (2) and (4) (52 P.S. 1406.5d(a)(1), (2) and (4)); 5.4(b) (52 P.S. 1406.5d(b)); 5.5(a...

  8. 30 CFR 938.15 - Approval of Pennsylvania regulatory program amendments.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Subsidence and Land 2001 Conservation Act: Repeal of Section 4 (52 P.S. 1406.4); 5(b)(partial approval); 5.1...)); 5.2(a)(1), (2), and (3) (52 P.S. 1406.5b(a)(1), (2), and (3)); 5.2(b)(1) (52 P.S. 1406.5b(b)(1)); 5... approval); 5.4(a)(1), (2) and (4) (52 P.S. 1406.5d(a)(1), (2) and (4)); 5.4(b) (52 P.S. 1406.5d(b)); 5.5(a...

  9. 30 CFR 938.15 - Approval of Pennsylvania regulatory program amendments.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Subsidence and Land 2001 Conservation Act: Repeal of Section 4 (52 P.S. 1406.4); 5(b)(partial approval); 5.1...)); 5.2(a)(1), (2), and (3) (52 P.S. 1406.5b(a)(1), (2), and (3)); 5.2(b)(1) (52 P.S. 1406.5b(b)(1)); 5... approval); 5.4(a)(1), (2) and (4) (52 P.S. 1406.5d(a)(1), (2) and (4)); 5.4(b) (52 P.S. 1406.5d(b)); 5.5(a...

  10. Regulatory Considerations for the Approval of Drugs Against Histomoniasis (Blackhead Disease) in Turkeys, Chickens, and Game Birds in the United States.

    PubMed

    Regmi, Prajwal R; Shaw, Ashley L; Hungerford, Laura L; Messenheimer, Janis R; Zhou, Tong; Pillai, Padmakumar; Omer, Amy; Gilbert, Jeffrey M

    2016-12-01

    Histomoniasis, commonly referred to as blackhead disease, is a serious threat to the turkey and game bird industries worldwide, and it is having an increasingly negative impact on the chicken industry as well. The Food and Drug Administration's (FDA) Center for Veterinary Medicine (CVM), charged with the approval and regulation of new animal drugs in the United States, understands the rising need for the availability of therapeutic options against histomoniasis. CVM has actively engaged in discussions with the poultry industry, academic institutions, and animal health companies regarding the current status of histomoniasis in the United States and varied success of past and current management, prophylactic, and therapeutic interventions that have been used against the disease. As effective options against the disease are severely limited, CVM encourages the poultry industry, academic institutions, and animal health companies to work together to research and develop viable management, prophylactic, and therapeutic strategies, such as litter management, deworming programs, vaccines or other biologics, novel technologies, and animal drugs. CVM also recognizes the potential challenges that the poultry industry, academic institutions, and animal health companies may encounter while working towards the approval of safe and effective drug products for the treatment and control of histomoniasis. With that recognition, CVM encourages interested parties to begin discussions with CVM early in order to align research of the drug product against histomoniasis with the drug approval requirements, such that it leads to the approval of a new animal drug in an efficient and expedient manner. This article provides information about the FDA's regulatory process for the approval of new animal drugs in the United States, with especial emphasis on drug products for the treatment and control of histomoniasis in turkeys, chickens, and game birds.

  11. 10 CFR 76.8 - Information collection requirements: OMB approval not required.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Information collection requirements: OMB approval not required. 76.8 Section 76.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS General Provisions § 76.8 Information collection requirements: OMB approval not required...

  12. 10 CFR 76.8 - Information collection requirements: OMB approval not required.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 2 2012-01-01 2012-01-01 false Information collection requirements: OMB approval not required. 76.8 Section 76.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS General Provisions § 76.8 Information collection requirements: OMB approval not required...

  13. 10 CFR 76.8 - Information collection requirements: OMB approval not required.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Information collection requirements: OMB approval not required. 76.8 Section 76.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS General Provisions § 76.8 Information collection requirements: OMB approval not required...

  14. 10 CFR 76.8 - Information collection requirements: OMB approval not required.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Information collection requirements: OMB approval not required. 76.8 Section 76.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS General Provisions § 76.8 Information collection requirements: OMB approval not required...

  15. 10 CFR 76.8 - Information collection requirements: OMB approval not required.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Information collection requirements: OMB approval not required. 76.8 Section 76.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS General Provisions § 76.8 Information collection requirements: OMB approval not required...

  16. 14 CFR 1230.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... consider possible long-range effects of applying knowledge gained in the research (for example, the... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Criteria for IRB approval of research. 1230... HUMAN SUBJECTS § 1230.111 Criteria for IRB approval of research. (a) In order to approve research...

  17. 16 CFR 1028.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... consider possible long-range effects of applying knowledge gained in the research (for example, the... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Criteria for IRB approval of research. 1028... HUMAN SUBJECTS § 1028.111 Criteria for IRB approval of research. (a) In order to approve research...

  18. 30 CFR 917.16 - Required regulatory program amendments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... to clarify that the total volume of flow from the proposed permit area, during every season of the... parties to be notified of the cabinet's decision to approve or deny the application for an operator change and to require that the regulatory authority be notified when the approved change is consummated. (i...

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

    PubMed

    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.

  20. 18 CFR 131.20 - Application for approval of transfer of license.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY APPROVED FORMS, FEDERAL POWER ACT AND PUBLIC UTILITY... quadruplicate, together with one additional copy for each interested State commission) Before the Federal Energy... the Federal Energy Regulatory Commission of the transfer of the aforesaid license from the transferor...

  1. 49 CFR 11.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... long-range effects of applying knowledge gained in the research (for example, the possible effects of... 49 Transportation 1 2010-10-01 2010-10-01 false Criteria for IRB approval of research. 11.111....111 Criteria for IRB approval of research. (a) In order to approve research covered by this policy the...

  2. 15 CFR 27.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... consider possible long-range effects of applying knowledge gained in the research (for example, the... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Criteria for IRB approval of research... HUMAN SUBJECTS § 27.111 Criteria for IRB approval of research. (a) In order to approve research covered...

  3. 28 CFR 46.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... possible long-range effects of applying knowledge gained in the research (for example, the possible effects... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Criteria for IRB approval of research. 46... SUBJECTS § 46.111 Criteria for IRB approval of research. (a) In order to approve research covered by this...

  4. 22 CFR 225.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... long-range effects of applying knowledge gained in the research (for example, the possible effects of... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Criteria for IRB approval of research. 225.111....111 Criteria for IRB approval of research. (a) In order to approve research covered by this policy the...

  5. 76 FR 78706 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  6. Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010.

    PubMed

    Downing, Nicholas S; Shah, Nilay D; Aminawung, Jenerius A; Pease, Alison M; Zeitoun, Jean-David; Krumholz, Harlan M; Ross, Joseph S

    2017-05-09

    Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near-regulatory deadline approval, and regulatory review time. A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001

  7. Investigating the state of physiologically based kinetic modelling practices and challenges associated with gaining regulatory acceptance of model applications.

    PubMed

    Paini, Alicia; Leonard, Jeremy A; Kliment, Tomas; Tan, Yu-Mei; Worth, Andrew

    2017-11-01

    Physiologically based kinetic (PBK) models are used widely throughout a number of working sectors, including academia and industry, to provide insight into the dosimetry related to observed adverse health effects in humans and other species. Use of these models has increased over the last several decades, especially in conjunction with emerging alternative methods to animal testing, such as in vitro studies and data-driven in silico quantitative-structure-activity-relationship (QSAR) predictions. Experimental information derived from these new approach methods can be used as input for model parameters and allows for increased confidence in models for chemicals that did not have in vivo data for model calibration. Despite significant advancements in good modelling practice (GMP) for model development and evaluation, there remains some reluctance among regulatory agencies to use such models during the risk assessment process. Here, the results of a survey disseminated to the modelling community are presented in order to inform the frequency of use and applications of PBK models in science and regulatory submission. Additionally, the survey was designed to identify a network of investigators involved in PBK modelling and knowledgeable of GMP so that they might be contacted in the future for peer review of PBK models, especially in regards to vetting the models to such a degree as to gain a greater acceptance for regulatory purposes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. 30 CFR 948.15 - Approval of West Virginia regulatory program amendments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) except the words “other responsible party” at (e) are not approved, .5, -13, -14.5, .8, .11, .12, .14... (f); 22-3-13a, in 13a(g) the words “upon request” are not approved, in 13a(j)(2) the phrase “or the... 17, 2004 CSR 38-2-7.4.b.1.I. March 25, 2004 February 8, 2005 CSR 38-2-3.12.a.1; 7.6 (except the word...

  9. 7 CFR 1717.304 - State regulatory authority rate jurisdiction.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... GUARANTEED ELECTRIC LOANS Federal Pre-emption in Rate Making in Connection With Power Supply Borrowers § 1717... terms of the RUS wholesale power contract or other RUS documents may be subject to the approval of a state regulatory authority, the power supply borrower shall seek such required approval in a timely...

  10. 7 CFR 1717.304 - State regulatory authority rate jurisdiction.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... GUARANTEED ELECTRIC LOANS Federal Pre-emption in Rate Making in Connection With Power Supply Borrowers § 1717... terms of the RUS wholesale power contract or other RUS documents may be subject to the approval of a state regulatory authority, the power supply borrower shall seek such required approval in a timely...

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

    PubMed

    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

  12. Japan-Specific Key Regulatory Aspects for Development of New Biopharmaceutical Drug Products.

    PubMed

    Desai, Kashappa Goud; Obayashi, Hirokazu; Colandene, James D; Nesta, Douglas P

    2018-03-28

    Japan represents the third largest pharmaceutical market in the world. Developing a new biopharmaceutical drug product for the Japanese market is a top business priority for global pharmaceutical companies while aligning with ethical drivers to treat more patients in need. Understanding Japan-specific key regulatory requirements is essential to achieve successful approvals. Understanding the full context of Japan-specific regulatory requirements/expectations is challenging to global pharmaceutical companies due to differences in language and culture. This article summarizes key Japan-specific regulatory aspects/requirements/expectations applicable to new drug development, approval, and postapproval phases. Formulation excipients should meet Japan compendial requirements with respect to the type of excipient, excipient grade, and excipient concentration. Preclinical safety assessments needed to support clinical phases I, II, and III development are summarized. Japanese regulatory authorities have taken appropriate steps to consider foreign clinical data, thereby enabling accelerated drug development and approval in Japan. Other important topics summarized in this article include: Japan new drug application-specific bracketing strategies for critical and noncritical aspects of the manufacturing process, regulatory requirements related to stability studies, release specifications and testing methods, standard processes involved in pre and postapproval inspections, management of postapproval changes, and Japan regulatory authority's consultation services available to global pharmaceutical companies. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  13. 10 CFR 20.2002 - Method for obtaining approval of proposed disposal procedures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Method for obtaining approval of proposed disposal procedures. 20.2002 Section 20.2002 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2002 Method for obtaining approval of proposed disposal procedures. A licensee...

  14. 10 CFR 20.2002 - Method for obtaining approval of proposed disposal procedures.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Method for obtaining approval of proposed disposal procedures. 20.2002 Section 20.2002 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2002 Method for obtaining approval of proposed disposal procedures. A licensee...

  15. 10 CFR 20.2002 - Method for obtaining approval of proposed disposal procedures.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Method for obtaining approval of proposed disposal procedures. 20.2002 Section 20.2002 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2002 Method for obtaining approval of proposed disposal procedures. A licensee...

  16. 10 CFR 20.2002 - Method for obtaining approval of proposed disposal procedures.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Method for obtaining approval of proposed disposal procedures. 20.2002 Section 20.2002 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2002 Method for obtaining approval of proposed disposal procedures. A licensee...

  17. 10 CFR 20.2002 - Method for obtaining approval of proposed disposal procedures.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Method for obtaining approval of proposed disposal procedures. 20.2002 Section 20.2002 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2002 Method for obtaining approval of proposed disposal procedures. A licensee...

  18. 75 FR 67421 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-02

    ... change to amend its By-Laws to remove the exemption from the trading activity fee (``TAF'') for... the exemption from the TAF for transactions in exchange listed options effected by a member for whom FINRA is not the DOEA. The TAF is one of three member regulatory fees FINRA uses to fund its member...

  19. Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010

    PubMed Central

    Downing, Nicholas S.; Shah, Nilay D.; Aminawung, Jenerius A.; Pease, Alison M.; Zeitoun, Jean-David; Krumholz, Harlan M.

    2017-01-01

    Importance Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. Objectives To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Design and Setting Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Exposures Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near–regulatory deadline approval, and regulatory review time. Main Outcomes and Measures A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. Results From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for

  20. 7 CFR 1c.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... long-range effects of applying knowledge gained in the research (for example, the possible effects of... 7 Agriculture 1 2010-01-01 2010-01-01 false Criteria for IRB approval of research. 1c.111 Section... Criteria for IRB approval of research. (a) In order to approve research covered by this policy the IRB...

  1. 2016 in review: FDA approvals of new molecular entities.

    PubMed

    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.

  2. 78 FR 76829 - Approval of Application Submitted by Eastern Shoshone Tribe and Northern Arapaho Tribe for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-19

    ... regulatory authority under the Clean Air Act. DATES: EPA's decision approving the Tribes' TAS application was... Decision Document, Attachment 1 (Legal Analysis of the Wind River Indian Reservation Boundary), Attachment... decision to approve the application does not approve, Tribal authority to implement any Clean Air Act...

  3. 75 FR 15470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

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

    PubMed

    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

  5. 17 CFR 1.52 - Self-regulatory organization adoption and surveillance of minimum financial requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 1 2011-04-01 2011-04-01 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...

  6. 17 CFR 1.52 - Self-regulatory organization adoption and surveillance of minimum financial requirements.

    Code of Federal Regulations, 2010 CFR

    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...

  7. 17 CFR 1.52 - Self-regulatory organization adoption and surveillance of minimum financial requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 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...

  8. Incorporating patient-preference evidence into regulatory decision making.

    PubMed

    Ho, Martin P; Gonzalez, Juan Marcos; Lerner, Herbert P; Neuland, Carolyn Y; Whang, Joyce M; McMurry-Heath, Michelle; Hauber, A Brett; Irony, Telba

    2015-10-01

    Patients have a unique role in deciding what treatments should be available for them and regulatory agencies should take their preferences into account when making treatment approval decisions. This is the first study designed to obtain quantitative patient-preference evidence to inform regulatory approval decisions by the Food and Drug Administration Center for Devices and Radiological Health. Five-hundred and forty United States adults with body mass index (BMI) ≥ 30 kg/m(2) evaluated tradeoffs among effectiveness, safety, and other attributes of weight-loss devices in a scientific survey. Discrete-choice experiments were used to quantify the importance of safety, effectiveness, and other attributes of weight-loss devices to obese respondents. A tool based on these measures is being used to inform benefit-risk assessments for premarket approval of medical devices. Respondent choices yielded preference scores indicating their relative value for attributes of weight-loss devices in this study. We developed a tool to estimate the minimum weight loss acceptable by a patient to receive a device with a given risk profile and the maximum mortality risk tolerable in exchange for a given weight loss. For example, to accept a device with 0.01 % mortality risk, a risk tolerant patient will require about 10 % total body weight loss lasting 5 years. Patient preference evidence was used make regulatory decision making more patient-centered. In addition, we captured the heterogeneity of patient preferences allowing market approval of effective devices for risk tolerant patients. CDRH is using the study tool to define minimum clinical effectiveness to evaluate new weight-loss devices. The methods presented can be applied to a wide variety of medical products. This study supports the ongoing development of a guidance document on incorporating patient preferences into medical-device premarket approval decisions.

  9. 5 CFR 470.311 - Final project approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... MANAGEMENT RESEARCH PROGRAMS AND DEMONSTRATIONS PROJECTS Regulatory Requirements Pertaining to Demonstration Projects § 470.311 Final project approval. (a) The Office of Personnel Management will consider all timely...) The Office of Personnel Management shall provide a copy of the final version of the project plan to...

  10. 78 FR 29190 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-17

    ... entered into an order management system (including orders received via telephone or instant message) and... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69561; File No. SR-FINRA-2013-013] Self..., 2013, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange...

  11. 7 CFR 1425.4 - Approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COOPERATIVE MARKETING ASSOCIATIONS § 1425.4 Approval. (a) For a cooperative to gain CMA status to participate in a marketing assistance loan or Loan deficiency... prepared in accordance with generally accepted accounting principles; (3) A copy of the articles of...

  12. 77 FR 63311 - Acacia Natural Gas Corporation; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  13. 10 CFR 76.62 - Issuance of certificate and/or approval of compliance plan.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 2 2012-01-01 2012-01-01 false Issuance of certificate and/or approval of compliance plan. 76.62 Section 76.62 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.62 Issuance of certificate and/or approval of compliance plan. (a) Upon...

  14. 10 CFR 76.62 - Issuance of certificate and/or approval of compliance plan.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Issuance of certificate and/or approval of compliance plan. 76.62 Section 76.62 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.62 Issuance of certificate and/or approval of compliance plan. (a) Upon...

  15. 10 CFR 76.62 - Issuance of certificate and/or approval of compliance plan.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Issuance of certificate and/or approval of compliance plan. 76.62 Section 76.62 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.62 Issuance of certificate and/or approval of compliance plan. (a) Upon...

  16. 10 CFR 76.62 - Issuance of certificate and/or approval of compliance plan.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Issuance of certificate and/or approval of compliance plan. 76.62 Section 76.62 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.62 Issuance of certificate and/or approval of compliance plan. (a) Upon...

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

    PubMed

    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.

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

    PubMed

    Kozarewicz, Piotr; Loftsson, Thorsteinn

    2018-05-21

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

  19. 76 FR 48937 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-09

    ... Trading Activity Fee (``TAF''). Certain transactions and transfers of securities are not required to be... transaction fees under Section 3 or the TAF.\\6\\ \\6\\ FINRA explained that this exception was adopted to align... regulatory transaction fees under Section 3 or the TAF. \\9\\ Rule 5190 imposes certain notice requirements on...

  20. 77 FR 68118 - TexStar Transmission, LP; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-15

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [ Docket No. PR13-4-000] TexStar Transmission, LP; Notice of Petition for Rate Approval Take notice that on November 2, 2012, TexStar Transmission, LP (TexStar) filed a Petition for Rate Approval pursuant to 284.123(b)(2) of the Commissions...

  1. 7 CFR 1425.4 - Approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... methods of conducting CCC loan and LDP business. (b) A CMA must submit, on an annual basis, the following... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COOPERATIVE MARKETING ASSOCIATIONS § 1425.4 Approval. (a) For a cooperative to gain CMA status to participate in a marketing assistance loan or Loan deficiency...

  2. 7 CFR 1425.4 - Approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... methods of conducting CCC loan and LDP business. (b) A CMA must submit, on an annual basis, the following... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COOPERATIVE MARKETING ASSOCIATIONS § 1425.4 Approval. (a) For a cooperative to gain CMA status to participate in a marketing assistance loan or Loan deficiency...

  3. 7 CFR 1425.4 - Approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... methods of conducting CCC loan and LDP business. (b) A CMA must submit, on an annual basis, the following... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COOPERATIVE MARKETING ASSOCIATIONS § 1425.4 Approval. (a) For a cooperative to gain CMA status to participate in a marketing assistance loan or Loan deficiency...

  4. 7 CFR 1425.4 - Approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... methods of conducting CCC loan and LDP business. (b) A CMA must submit, on an annual basis, the following... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COOPERATIVE MARKETING ASSOCIATIONS § 1425.4 Approval. (a) For a cooperative to gain CMA status to participate in a marketing assistance loan or Loan deficiency...

  5. Meeting Regulatory Needs.

    PubMed

    Weber, Michael Fred

    2017-02-01

    The world is experiencing change at an unprecedented pace, as reflected in social, cultural, economic, political, and technological advances around the globe. Regulatory agencies, like the U.S. Nuclear Regulatory Commission (NRC), must also transform in response to and in preparation for these changes. In 2014, the NRC staff commenced Project Aim 2020 to transform the agency by enhancing efficiency, agility, and responsiveness, while accomplishing NRC's safety and security mission. Following Commission review and approval in 2015, the NRC began implementing the approved strategies, including strategic workforce planning to provide confidence that NRC will have employees with the right skills and talents at the right time to accomplish the agency's mission. Based on the work conducted so far, ensuring an adequate pipeline of radiation protection professionals is a significant need that NRC shares with states and other government agencies, private industry, academia, as well as international counterparts. NRC is working to ensure that sufficient radiation protection professionals will be available to fulfill its safety and security mission and leverage the work of the National Council on Radiation Protection and Measurements, the Conference of Radiation Control Program Directors, the Health Physics Society, the Organization of Agreement States, the International Atomic Energy Agency, the Nuclear Energy Agency, and others.

  6. Capacity for ethical and regulatory review of herbal trials in developing countries: a case study of Moringa oleifera research in HIV-infected patients.

    PubMed

    Monera-Penduka, Tsitsi G; Maponga, Charles C; Morse, Gene D; Nhachi, Charles F B

    2017-01-01

    Lack of regulatory capacity limits the conduct of ethical and rigorous trials of herbal medicines in developing countries. Sharing ethical and regulatory experiences of successful herbal trials may accelerate the field while assuring human subjects protection. The methods and timelines for the ethical and regulatory review processes for the first drug regulatory authority approved herbal trial in Zimbabwe are described in this report. The national drug regulatory authority and ethics committee were engaged for pre-submission discussions. Six applications were submitted. Application procedures and communications with the various regulatory and ethics review boards were reviewed. Key issues raised and timelines for communications were summarized. There was no special framework for the approval of herbal trials. One local institutional review committee granted an exemption. Key issues raised for revision were around pre-clinical efficacy and safety data, standardization and quality assurance of the intervention as well as consenting procedures. Approval timelines ranged between eight and 72 weeks. In the absence of a defined framework for review of herbal trials, approval processes can be delayed. Dialogue between researchers and regulators is important for successful and efficient protocol approval for herbal trials in developing countries. The study was registered prospectively on August 3, 2011 with clinicaltrials.gov (NCT01410058).

  7. Glycoconjugate Vaccines: The Regulatory Framework.

    PubMed

    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.

  8. 78 FR 6356 - Notice of Consideration of Approval of Application Regarding Proposed Indirect Transfer of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ... NUCLEAR REGULATORY COMMISSION [Docket No. 070-3098; NRC-2011-0081] Notice of Consideration of Approval of Application Regarding Proposed Indirect Transfer of Control of the Construction Authorization for the Mixed Oxide Fuel Fabrication Facility in Aiken, SC; Correction AGENCY: Nuclear Regulatory...

  9. Translation of proteomic biomarkers into FDA approved cancer diagnostics: issues and challenges

    PubMed Central

    2013-01-01

    Tremendous efforts have been made over the past few decades to discover novel cancer biomarkers for use in clinical practice. However, a striking discrepancy exists between the effort directed toward biomarker discovery and the number of markers that make it into clinical practice. One of the confounding issues in translating a novel discovery into clinical practice is that quite often the scientists working on biomarker discovery have limited knowledge of the analytical, diagnostic, and regulatory requirements for a clinical assay. This review provides an introduction to such considerations with the aim of generating more extensive discussion for study design, assay performance, and regulatory approval in the process of translating new proteomic biomarkers from discovery into cancer diagnostics. We first describe the analytical requirements for a robust clinical biomarker assay, including concepts of precision, trueness, specificity and analytical interference, and carryover. We next introduce the clinical considerations of diagnostic accuracy, receiver operating characteristic analysis, positive and negative predictive values, and clinical utility. We finish the review by describing components of the FDA approval process for protein-based biomarkers, including classification of biomarker assays as medical devices, analytical and clinical performance requirements, and the approval process workflow. While we recognize that the road from biomarker discovery, validation, and regulatory approval to the translation into the clinical setting could be long and difficult, the reward for patients, clinicians and scientists could be rather significant. PMID:24088261

  10. 30 CFR 795.8 - Application approval and notice.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Application approval and notice. 795.8 Section 795.8 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR SMALL OPERATOR ASSISTANCE PERMANENT REGULATORY PROGRAM-SMALL OPERATOR ASSISTANCE PROGRAM § 795.8...

  11. Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

    PubMed

    Gonçalves, Joana P; Aires, Ricardo S; Francisco, Alexandre P; Madeira, Sara C

    2012-01-01

    Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched

  12. Regulatory Snapshots: Integrative Mining of Regulatory Modules from Expression Time Series and Regulatory Networks

    PubMed Central

    Gonçalves, Joana P.; Aires, Ricardo S.; Francisco, Alexandre P.; Madeira, Sara C.

    2012-01-01

    Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched

  13. The Ethics and Politics of Ethics Approval

    ERIC Educational Resources Information Center

    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…

  14. 18 CFR 12.34 - Approval of independent consultant.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... consultant. 12.34 Section 12.34 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT SAFETY OF WATER POWER PROJECTS AND... Director of the Office of Energy Projects Licensing for approval, with a copy to the Regional Engineer, a...

  15. 18 CFR 12.34 - Approval of independent consultant.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... consultant. 12.34 Section 12.34 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT SAFETY OF WATER POWER PROJECTS AND... Director of the Office of Energy Projects Licensing for approval, with a copy to the Regional Engineer, a...

  16. 18 CFR 12.34 - Approval of independent consultant.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... consultant. 12.34 Section 12.34 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT SAFETY OF WATER POWER PROJECTS AND... Director of the Office of Energy Projects Licensing for approval, with a copy to the Regional Engineer, a...

  17. 18 CFR 12.34 - Approval of independent consultant.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... consultant. 12.34 Section 12.34 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT SAFETY OF WATER POWER PROJECTS AND... Director of the Office of Energy Projects Licensing for approval, with a copy to the Regional Engineer, a...

  18. 18 CFR 12.34 - Approval of independent consultant.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... consultant. 12.34 Section 12.34 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT SAFETY OF WATER POWER PROJECTS AND... Director of the Office of Energy Projects Licensing for approval, with a copy to the Regional Engineer, a...

  19. 18 CFR 300.10 - Application for confirmation and approval.

    Code of Federal Regulations, 2010 CFR

    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...

  20. 10 CFR 34.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Information collection requirements: OMB approval. 34.8 Section 34.8 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS General Provisions § 34.8 Information collection...

  1. 10 CFR 34.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Information collection requirements: OMB approval. 34.8 Section 34.8 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS General Provisions § 34.8 Information collection...

  2. 10 CFR 34.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Information collection requirements: OMB approval. 34.8 Section 34.8 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS General Provisions § 34.8 Information collection...

  3. 10 CFR 34.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Information collection requirements: OMB approval. 34.8 Section 34.8 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS General Provisions § 34.8 Information collection...

  4. 10 CFR 34.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 34.8 Section 34.8 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS General Provisions § 34.8 Information collection...

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

    PubMed

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

    2018-05-08

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

  6. Regulatory element-based prediction identifies new susceptibility regulatory variants for osteoporosis.

    PubMed

    Yao, Shi; Guo, Yan; Dong, Shan-Shan; Hao, Ruo-Han; Chen, Xiao-Feng; Chen, Yi-Xiao; Chen, Jia-Bin; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

    2017-08-01

    Despite genome-wide association studies (GWASs) have identified many susceptibility genes for osteoporosis, it still leaves a large part of missing heritability to be discovered. Integrating regulatory information and GWASs could offer new insights into the biological link between the susceptibility SNPs and osteoporosis. We generated five machine learning classifiers with osteoporosis-associated variants and regulatory features data. We gained the optimal classifier and predicted genome-wide SNPs to discover susceptibility regulatory variants. We further utilized Genetic Factors for Osteoporosis Consortium (GEFOS) and three in-house GWASs samples to validate the associations for predicted positive SNPs. The random forest classifier performed best among all machine learning methods with the F1 score of 0.8871. Using the optimized model, we predicted 37,584 candidate SNPs for osteoporosis. According to the meta-analysis results, a list of regulatory variants was significantly associated with osteoporosis after multiple testing corrections and contributed to the expression of known osteoporosis-associated protein-coding genes. In summary, combining GWASs and regulatory elements through machine learning could provide additional information for understanding the mechanism of osteoporosis. The regulatory variants we predicted will provide novel targets for etiology research and treatment of osteoporosis.

  7. 18 CFR 11.13 - Energy gains calculations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Energy gains calculations. 11.13 Section 11.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT ANNUAL CHARGES UNDER PART I OF THE...

  8. 18 CFR 11.13 - Energy gains calculations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Energy gains calculations. 11.13 Section 11.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT ANNUAL CHARGES UNDER PART I OF THE...

  9. 18 CFR 11.13 - Energy gains calculations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Energy gains calculations. 11.13 Section 11.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT ANNUAL CHARGES UNDER PART I OF THE...

  10. 18 CFR 11.13 - Energy gains calculations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Energy gains calculations. 11.13 Section 11.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT ANNUAL CHARGES UNDER PART I OF THE...

  11. 18 CFR 11.13 - Energy gains calculations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Energy gains calculations. 11.13 Section 11.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT ANNUAL CHARGES UNDER PART I OF THE...

  12. Accelerated approval of oncology products: a decade of experience.

    PubMed

    Dagher, Ramzi; Johnson, John; Williams, Grant; Keegan, Patricia; Pazdur, Richard

    2004-10-20

    We review the regulatory history of the accelerated approval process and summarize the U.S. Food and Drug Administration experience with accelerated approvals in oncology. The accelerated approval regulations, promulgated in 1992, allow approval of drugs for serious or life-threatening diseases on the basis of a surrogate endpoint that is reasonably likely to predict clinical benefit, such as survival or symptom benefit, pending completion of studies designed to confirm clinical benefit, referred to as phase 4 commitments, which are required to be conducted with due diligence. From 1992 to 2004, 22 applications involving anticancer drugs or biologics were approved. Of these 22 applications, accelerated approval was granted to 15 on the basis of findings from studies without an active comparator (i.e., single-arm studies or studies comparing two dose levels) and to the remaining seven on the basis of one or more randomized studies. Of the 22 approved applications, six (i.e., applications for dexrazoxane, irinotecan, capecitabine, docetaxel, imatinib mesylate, and oxaliplatin) have had one or more indications converted to regular approval. This review reports information that was presented at an Oncologic Drugs Advisory Committee meeting held in March 2003; it also presents a discussion of accelerated approval study designs, the study populations evaluated in the accelerated approval and confirmatory settings, and the integration of accelerated approval into a comprehensive drug development plan.

  13. Regulatory considerations in the clinical development of vaccines indicated for use during pregnancy.

    PubMed

    Roberts, Jeffrey N; Gruber, Marion F

    2015-02-18

    Despite supportive public health policies (e.g., ACIP recommendations), the potential for providing clinical benefit through maternal immunization has yet to be fully realized. For vaccines already licensed and approved for use in adults, specific FDA approval for use during pregnancy to prevent disease in the mother and/or infant may have a significant impact on uptake and usage in pregnant women. In addition, for either a licensed vaccine or a novel vaccine, FDA approval for use during pregnancy would result in labeling that would serve as a resource for practitioners and would facilitate the safe and effective use of the vaccine during pregnancy. In the U.S., while many vaccines are approved for use in adults and most are not contraindicated for use in pregnant women, no vaccine is licensed for use specifically during pregnancy. Among the perceived obstacles hindering the clinical development of vaccines for use in pregnancy, regulatory issues are frequently cited. One aim of this article is to address the perceived regulatory obstacles. General concepts and regulatory considerations for clinical safety and effectiveness evaluations for vaccines indicated for use during pregnancy will be discussed. This discussion is not intended to establish data requirements or to articulate agency policy or guidance regarding specific vaccine products. Published by Elsevier Ltd.

  14. Goals-feedback conditions and episodic memory: Mechanisms for memory gains in older and younger adults.

    PubMed

    West, Robin L; Dark-Freudeman, Alissa; Bagwell, Dana K

    2009-02-01

    Research has established that challenging memory goals always lead to score increases for younger adults, and can increase older adults' scores under supportive conditions. This study examined beliefs and on-task effort as potential mechanisms for these self-regulatory gains, in particular to learn whether episodic memory gains across multiple trials of shopping list recall are controlled by the same factors for young and old people. Goals with feedback led to higher recall and strategic categorisation than a control condition. Strategy usage was the strongest predictor of gains over trials for both age groups. Age, goal condition, and effort also predicted scores across the entire sample. Older adults' gains, but not younger adults' gains, were affected significantly by the interaction of self-efficacy beliefs and goal condition, and condition interacted with locus of control to predict younger adult gains. These results emphasise the importance of self-regulatory effort and positive beliefs for facilitating goal-related memory gains.

  15. An FDA Perspective on the Regulatory Implications of Complex Signatures to Predict Response to Targeted Therapies

    PubMed Central

    Beaver, Julia A.; Tzou, Abraham; Blumenthal, Gideon M.; McKee, Amy E.; Kim, Geoffrey; Pazdur, Richard; Philip, Reena

    2016-01-01

    As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation. We also will review the potential regulatory pathways for clearance, approval, or acceptance of complex signatures by the U.S. Food and Drug Administration (FDA). These regulatory pathways include regulations applicable to in vitro diagnostic devices, including companion diagnostic devices, the potential for labeling as a complementary diagnostic, and the biomarker qualification program. PMID:27993967

  16. 30 CFR 934.15 - Approval of North Dakota regulatory program amendments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... dates amendments were submitted to OSM, the dates when the Director's decision approving all, or..., Wetlands standards. II-I, Recreational land use standards for tree and shrub stocking. III-D, Methods for...

  17. 77 FR 12089 - Proposed Generic Communication; Regulatory Issue Summary 2012-XX: Developing Inservice Testing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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. 18 CFR 300.21 - Final confirmation and approval.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Final confirmation and approval. 300.21 Section 300.21 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... reasonable number of years after first meeting the Administrator's other costs. (ii) The rates must be based...

  19. 18 CFR 300.21 - Final confirmation and approval.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Final confirmation and approval. 300.21 Section 300.21 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... reasonable number of years after first meeting the Administrator's other costs. (ii) The rates must be based...

  20. 10 CFR 33.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 33.8 Section 33.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT..., 1997; 67 FR 67099, Nov. 4, 2002] Specific Licenses of Broad Scope ...

  1. 10 CFR 33.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Information collection requirements: OMB approval. 33.8 Section 33.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT..., 1997; 67 FR 67099, Nov. 4, 2002] Specific Licenses of Broad Scope ...

  2. 10 CFR 33.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Information collection requirements: OMB approval. 33.8 Section 33.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT..., 1997; 67 FR 67099, Nov. 4, 2002] Specific Licenses of Broad Scope ...

  3. 10 CFR 33.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Information collection requirements: OMB approval. 33.8 Section 33.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT..., 1997; 67 FR 67099, Nov. 4, 2002] Specific Licenses of Broad Scope ...

  4. 10 CFR 33.8 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Information collection requirements: OMB approval. 33.8 Section 33.8 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT..., 1997; 67 FR 67099, Nov. 4, 2002] Specific Licenses of Broad Scope ...

  5. 76 FR 11776 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-03

    ... Activities; Submission to OMB for Review and Approval; Comment Request; Regulatory Pilot Projects (Renewal... Management and Budget (OMB), Attention: Desk Officer for EPA, 725 17th Street, NW., Washington, DC 20503. FOR... information about the electronic docket, go to http://www.regulations.gov . Title: Regulatory Pilot Projects...

  6. Avelumab: First Global Approval.

    PubMed

    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.

  7. Case studies with new excipients: development, implementation and regulatory approval.

    PubMed

    Koo, Otilia M Y; Varia, Sailesh A

    2011-07-01

    The purpose of this article is to describe the process whereby new excipients become accepted and to describe three case studies to illustrate the process. New excipients are defined according to the 2005 FDA Guidance on Nonclinical Safety Evaluation of New Excipients. The requirements for safety data submission for new excipients used in different classes of products for different durations are outlined in the guidance. Currently, the development of new excipients is linked to the development and approval of new drug products that contain them. New excipients that are used in US-approved drug products become listed in the FDA Inactive Ingredients Guide (IIG) database. Thereafter, US Pharmacopeia monographs for the new excipients are proposed. New excipients are reviewed and become accepted in the same way in Europe and Japan, except that there is no equivalent IIG database. Therefore, the focus of this article will be on the FDA review process. Three case studies, polyoxyl 15 hydroxystearate, sulfobutyl ether cyclodextrin and silicified microcrystalline cellulose, are used to illustrate how new excipients are accepted and implemented.

  8. A comparison of new drugs approved by the FDA, the EMA, and Swissmedic: an assessment of the international harmonization of drugs.

    PubMed

    Zeukeng, Minette-Joëlle; Seoane-Vazquez, Enrique; Bonnabry, Pascal

    2018-06-01

    This study compared the characteristics of new human drugs approved by the Food and Drug Administration (FDA), the European Medicine Agency (EMA), and Swissmedic (SMC) in the period 2007 to 2016. The list of new drugs and therapeutic biologics approved by the FDA, the EMA, and SMC in the period 2007 to 2016 was collected from websites of those agencies. The study included regulatory information, approval date, and indication for each drug. Descriptive statistical t tests and x 2 -tests were performed for the analysis. From 2007 to 2016, 134 new drugs were approved by all three regulatory agencies. Overall, 66.4% of the drugs were first approved by the FDA, 30.6% by the EMA, and 3.0% by SMC. The difference in approval dates between SMC and the EMA, SMC and the FDA, and the FDA and the EMA were statistically significant. The indications approved by the FDA, the EMA, and SMC for the same drugs were similar in content for 23.1% drugs and different in 76.9% of the drugs. Significant differences in indications existed between the FDA and SMC and the FDA and the EMA, but not between the EMA and SMC. There were differences in the characteristics of new drugs approved by the EMA, the FDA, and SMC in the period 2007-2016. Overall, two thirds of the new drugs were first approved by the FDA. Differences in indications were found in three out of four new drugs approved by the three regulatory agencies. Despite international drug regulation harmonization efforts, significant differences in the characteristics of new drugs approved by different agencies persist.

  9. Impact of regulatory assessment on clinical studies in Brazil.

    PubMed

    Russo, Luis Augusto Tavares; Eliaschewitz, Freddy Goldberg; Harada, Vitor; Trefiglio, Roberta Pereira; Picciotti, Raffaella; Machado, Paula Goulart Pinheiro; Kesselring, Gustavo Luiz Ferreira

    2016-01-01

    Despite the recent expansion of clinical studies allocated to Brazil, the delay of local regulatory deadlines directly impacts their completion. This article examines the allocation process of clinical studies to Brazil in comparison with other countries, as well as the financial impact of studies not completed due to interruption caused by the delay in the regulatory process. The allocation processes of studies were compared in nine countries with similar stages of economic development and countries in Latin America using the websites http://data.worldbank.org/data-catalog/GDP-rankings-table and http://worldpopulationreview.com and clinicaltrials.gov, comprising 185 countries. The 46 studies sponsored by the pharmaceutical industry underwent an analysis of the regulatory review process. 46 studies sponsored by the industry and submitted in the country between June 2007 and June 2013 were analyzed; 18 (39%) were discontinued due to the delay in obtaining the necessary approvals. For the approved studies, patient recruitment began an average of 11 months after the other countries. It is estimated that 530 Brazilians patients did not have the opportunity to participate in these studies. Financial losses were to the order of 14.6 million dollars for the country, including patient, medication and supplies costs, and expenses. Brazil has enormous potential for the realization of clinical studies. Researchers, associations of disabled people and patients with chronic diseases, sponsors and the authorities must work together to develop an approval process that is efficient, predictable and, most of all, transparent. The current regulatory environment must and can be improved and optimized in order to result in tangible benefits for patients, society and the country's scientific development.

  10. Divergent genome evolution caused by regional variation in DNA gain and loss between human and mouse

    PubMed Central

    Kortschak, R. Daniel

    2018-01-01

    The forces driving the accumulation and removal of non-coding DNA and ultimately the evolution of genome size in complex organisms are intimately linked to genome structure and organisation. Our analysis provides a novel method for capturing the regional variation of lineage-specific DNA gain and loss events in their respective genomic contexts. To further understand this connection we used comparative genomics to identify genome-wide individual DNA gain and loss events in the human and mouse genomes. Focusing on the distribution of DNA gains and losses, relationships to important structural features and potential impact on biological processes, we found that in autosomes, DNA gains and losses both followed separate lineage-specific accumulation patterns. However, in both species chromosome X was particularly enriched for DNA gain, consistent with its high L1 retrotransposon content required for X inactivation. We found that DNA loss was associated with gene-rich open chromatin regions and DNA gain events with gene-poor closed chromatin regions. Additionally, we found that DNA loss events tended to be smaller than DNA gain events suggesting that they were able to accumulate in gene-rich open chromatin regions due to their reduced capacity to interrupt gene regulatory architecture. GO term enrichment showed that mouse loss hotspots were strongly enriched for terms related to developmental processes. However, these genes were also located in regions with a high density of conserved elements, suggesting that despite high levels of DNA loss, gene regulatory architecture remained conserved. This is consistent with a model in which DNA gain and loss results in turnover or “churning” in regulatory element dense regions of open chromatin, where interruption of regulatory elements is selected against. PMID:29677183

  11. 77 FR 75243 - Self-Regulatory Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    ... modeling and risk management procedures (``Risk Management Proposal'') \\9\\ is approved by the Commission.... The enhancements are part of OCC's ongoing efforts to test and improve its risk management operations... Index Options,\\12\\ and only subject to the filing and approval of the Risk Management Proposal, as...

  12. 77 FR 74043 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-12

    ... (``OCC'') submitted to the Securities and Exchange Commission (``Commission''), pursuant to Rule 9b-1... of trading standardized options. In September 2012, the Commission approved proposed rule changes...\\ The Commission recently approved a proposed rule change by the OCC to make similar changes to its By...

  13. 10 CFR 72.9 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Information collection requirements: OMB approval. 72.9 Section 72.9 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR THE INDEPENDENT STORAGE OF SPENT NUCLEAR FUEL, HIGH-LEVEL RADIOACTIVE WASTE, AND REACTOR-RELATED GREATER THAN CLASS C...

  14. 10 CFR 72.9 - Information collection requirements: OMB approval.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Information collection requirements: OMB approval. 72.9 Section 72.9 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR THE INDEPENDENT STORAGE OF SPENT NUCLEAR FUEL, HIGH-LEVEL RADIOACTIVE WASTE, AND REACTOR-RELATED GREATER THAN CLASS C...

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

    PubMed

    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.

  16. 77 FR 55887 - Self-Regulatory Organizations; the Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-11

    ... Organizations; the Options Clearing Corporation; Order Approving Proposed Rule Change To Amend OCC's By-Laws To... would amend OCC's By-Laws to allow the Corporation to approve OCC's form of clearing member application.... OCC's By- Laws and Rules set forth the qualifications and requirements for clearing membership at OCC...

  17. 77 FR 20870 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ... Definition of Approved Person To Exclude Foreign Affiliates, Eliminating the Application Process for Approved... to exclude foreign affiliates, eliminate the application process for approved persons, and make... Rules 304, 308, and 311. The Exchange also proposed to eliminate use of the Forms AP-1 and AD-G. The...

  18. The Regulatory Perspectives on Endoscopic Devices for Obesity.

    PubMed

    Marrone, April K; Antonino, Mark J; Silverstein, Joshua S; Betz, Martha W; Venkataraman-Rao, Priya; Golding, Martin; Cordray, Diane; Cooper, Jeffrey W

    2017-04-01

    The recent increase in US Food and Drug Administration-approved weight-loss devices has diversified obesity treatment options. The regulatory pathways for endoscopically placed weight-loss devices and considerations for clinical trials are discussed, including the benefit-risk paradigm intended to aid in weight-loss-device trial development. Also discussed is the benefit-risk analysis of recently approved endoscopic devices. A strategic priority of the FDA Center for Devices and Radiological Health is to increase the use of patient input in decision making. Thus, we consider how endoscopic weight-loss devices with profiles similar to those that have been approved may be viewed in a patient preference study. Published by Elsevier Inc.

  19. 77 FR 56241 - Notice of Withdrawal of Final Design Approval; Westinghouse Electric Company; Advanced Passive 1000

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-12

    ... NUCLEAR REGULATORY COMMISSION [NRC-2010-0131] Notice of Withdrawal of Final Design Approval... final design approval (FDA) for the Advanced Passive 1000 (AP1000) design upon the completion of rulemaking for the amendment to the AP1000 design and the issuance of the amended AP1000 design certification...

  20. Sebelipase alfa: first global approval.

    PubMed

    Shirley, Matt

    2015-11-01

    Sebelipase alfa (Kanuma™) is a recombinant human lysosomal acid lipase (LAL) developed by Synageva BioPharma Corp. (now Alexion Pharmaceuticals, Inc.) for long-term enzyme replacement therapy in patients with LAL deficiency. The agent, administered by intravenous infusion once weekly or once every other week, acts to replace the deficient enzyme activity in patients with LAL deficiency, reducing lysosomal lipid accumulation, and thereby improving disease-related abnormalities such as dyslipidaemia and liver abnormalities. Sebelipase alfa received its first global approval, in the EU, in August 2015 for long-term enzyme replacement therapy in patients of all ages with LAL deficiency. Regulatory submissions have also been filed in the USA, Mexico and Japan for use in this indication. This article summarizes the milestones in the development of sebelipase alfa leading to this first approval for the treatment of LAL deficiency.

  1. Regulatory pathways in the European Union.

    PubMed

    Kohler, Manuela

    2011-01-01

    In principle, there are three defined procedures to obtain approval for a medicinal product in the European Union. As discussed in this overview of the procedures, the decision on which regulatory pathway to use will depend on the nature of the active substance, the target indication(s), the history of product and/or the marketing strategy.

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

    PubMed

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

    2018-05-16

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

  3. Safinamide: first global approval.

    PubMed

    Deeks, Emma D

    2015-04-01

    Safinamide (Xadago(®)) is an oral α-aminoamide derivative developed by Newron for the treatment of Parkinson's disease (PD). The drug has both dopaminergic properties (highly selective and reversible inhibition of monoamine oxidase-B) and non-dopaminergic properties (selective sodium channel blockade and calcium channel modulation, with consequent inhibition of excessive glutamate release). Safinamide is approved in the EU, Iceland, Lichtenstein and Norway, as an add-on therapy to stable-dose levodopa, alone or in combination with other PD therapies in mid- to late-stage fluctuating PD patients; regulatory submissions have also been filed in the USA and Switzerland for its use in this indication. Additional submissions have been made in the USA, Iceland, Lichtenstein, Norway and Switzerland for early-stage PD. Safinamide has also undergone phase II investigation in PD patients with drug-induced dyskinesia (France, Germany, Austria, Canada and South Africa) or cognitive impairment (USA and Spain). This article summarizes the milestones in the development of safinamide leading to its first approval for PD.

  4. Semaglutide: First Global Approval.

    PubMed

    Dhillon, Sohita

    2018-02-01

    Novo Nordisk has developed a subcutaneous formulation of semaglutide (Ozempic ® ), a modified human glucagon-like peptide-1 (GLP-1) analogue, for the treatment of type 2 diabetes mellitus. It has been developed using Novo Nordisk's proprietary protein-acylation technology, and is administered using an injection device. Semaglutide lowers blood glucose by stimulating the release of insulin and also lowers body weight. Once-weekly subcutaneous semaglutide has recently been approved in the US, Puerto Rico and Canada, and has received a positive opinion in the EU for the treatment of patients with type 2 diabetes. It will be launched as the Ozempic ® Pen, a pre-filled device. Semaglutide is also under regulatory review in Japan and Switzerland for the treatment of type 2 diabetes. Clinical development for obesity, non-alcoholic steatohepatitis and non-alcoholic fatty liver disease is underway worldwide. This article summarizes the milestones in the development of semaglutide leading to this first approval for type 2 diabetes.

  5. Biosimilars: a regulatory perspective from America.

    PubMed

    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.

  6. School Site Selection and Approval Guide.

    ERIC Educational Resources Information Center

    California State Dept. of Education, Sacramento. Div. of School Facilities Planning.

    This guide is designed to assist school districts in selecting school sites that provide both a safe and supportive environment for the instructional program and the learning process, and gain state approval for the selected sites. The guide includes a set of selection criteria that have proven helpful to site selection teams, information about…

  7. Characteristics of rare disease marketing applications associated with FDA product approvals 2006-2010.

    PubMed

    Pariser, Anne R; Slack, Daniel J; Bauer, Larry J; Warner, Catherine A; Tracy, LaRee A

    2012-08-01

    New drug and biologic product marketing applications submitted to FDA's Center for Drug Evaluation and Research (CDER) between 2006 and 2010 were analyzed to identify rare disease application characteristics associated with higher approval rates. The results show that approval rates were similar for rare and common disease applications. Larger company size, prior regulatory experience and priority review designation were associated with higher approval rates. The study findings show that rare disease product development is feasible, and increased interactions between product developers and FDA in early investigational phases can facilitate product development. Published by Elsevier Ltd.

  8. The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb

    PubMed Central

    Cotney, Justin; Leng, Jing; Yin, Jun; Reilly, Steven K.; DeMare, Laura E.; Emera, Deena; Ayoub, Albert E.; Rakic, Pasko; Noonan, James P.

    2013-01-01

    SUMMARY The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human-specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis-regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find that 13% of promoters and 11% of enhancers have gained activity on the human lineage since the human-rhesus divergence. These gains largely arose by modification of ancestral regulatory activities in the limb or potential co-option from other tissues and are likely to have heterogeneous genetic causes. Most enhancers that exhibit gain of activity in humans originated in mammals. Gains at promoters and enhancers in the human limb are associated with increased gene expression, suggesting they include molecular drivers of human morphological evolution. PMID:23827682

  9. 76 FR 33651 - Approval and Promulgation of Implementation Plans; ID

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-09

    ... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [EPA-R10-OAR-2007-0406, FRL-9316-7] Approval and Promulgation of Implementation Plans; ID AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule... provide the Idaho Department of Environmental Quality (IDEQ) the regulatory authority to address regional...

  10. 78 FR 55765 - Compensatory and Alternative Regulatory Measures for Nuclear Power Plant Fire Protection (CARMEN...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-11

    ... Nuclear Power Plant Fire Protection (CARMEN-FIRE) AGENCY: Nuclear Regulatory Commission. ACTION: Draft..., ``Compensatory and Alternative Regulatory Measures for Nuclear Power Plant Fire Protection (CARMEN-FIRE).'' In... integral part of NRC-approved fire protection programs. However, compensatory measures are not expected to...

  11. 76 FR 81466 - Notice of Request for Extension of Approval of an Information Collection; Importation of Small...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... Seed AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Extension of approval of an... approval of an information collection associated with regulations for the importation of small lots of seed... Delivery: Send your comment to Docket No. APHIS-2011-0118, Regulatory Analysis and Development, PPD, APHIS...

  12. 10 CFR 70.23 - Requirements for the approval of applications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... and use special nuclear material in a plutonium processing and fuel fabrication plant. 3 The criteria... Section 70.23 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING OF SPECIAL NUCLEAR... a license will be approved if the Commission determines that: (1) The special nuclear material is to...

  13. 10 CFR 70.23 - Requirements for the approval of applications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and use special nuclear material in a plutonium processing and fuel fabrication plant. 3 The criteria... Section 70.23 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING OF SPECIAL NUCLEAR... a license will be approved if the Commission determines that: (1) The special nuclear material is to...

  14. 10 CFR 70.23 - Requirements for the approval of applications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... to possess and use special nuclear material in a plutonium processing and fuel fabrication plant. 3... Section 70.23 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING OF SPECIAL NUCLEAR... a license will be approved if the Commission determines that: (1) The special nuclear material is to...

  15. 10 CFR 70.23 - Requirements for the approval of applications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... and use special nuclear material in a plutonium processing and fuel fabrication plant. 3 The criteria... Section 70.23 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING OF SPECIAL NUCLEAR... a license will be approved if the Commission determines that: (1) The special nuclear material is to...

  16. Regulatory considerations for clinical development of cancer vaccines.

    PubMed

    Heelan, Bridget Theresa

    2014-01-01

    Cancer vaccines are aimed at stimulating an immune response to tumor tissue. There is a high level of clinical activity in this rapidly advancing field with over 1,400 trials registered on Clincaltrials.gov. The recent approval of Sipuleucel-T which is the first cancer vaccine approved in the US and EU has encouraged developers in this field. In contrast to more established approaches for treating cancer such as chemotherapy, regulatory guidelines have been developed relatively recently for cancer vaccines. These guidelines advise on general clinical requirements. As there is an increase in innovative strategies with novel products, a 2-way dialog with regulators is recommended on a case-by-case basis to justify the clinical development plan, taking into account specific quality issues related to the product(s) in development. It is important that the rationale, background and justification for the planned development is convincing when interacting with the regulatory authorities, to enable drug developers and regulators to reach agreement.

  17. 77 FR 20869 - Self-Regulatory Organizations; NYSE Amex LLC; Order Approving a Proposed Rule Change Amending the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ... Equities Definition of Approved Person To Exclude Foreign Affiliates, Eliminating the Application Process... Equities definition of approved person to exclude foreign affiliates, eliminate the application process for... amend the NYSE Amex Equities definition of ``approved person'' to exclude foreign affiliates, eliminate...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-06-01

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

  20. Overview of FDA approval paths optical surgical navigation

    NASA Astrophysics Data System (ADS)

    Jacobs, Paula M.

    2017-02-01

    The development of drugs and devices to guide surgical resection of tumors in the United States requires the approval of the US Food and Drug Administration. Because these combine a drug and a device, the regulatory pathways can be confusing, particularly to academics or small companies. This paper discusses some of the issues and provides some guidance in this area.

  1. Gender-specific Regulatory Challenges to Product Approval: A Panel Discussion

    PubMed Central

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

    2015-01-01

    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. PMID:25443664

  2. 30 CFR 938.12 - State statutory, regulatory, and proposed program amendment provisions not approved.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... provisions of the proposed program amendment that Pennsylvania submitted on July 29, 1998: (1) Section 5.1(b) (52 P.S. 1406.5a(b)) of BMSLCA is not approved to the extent noted in 30 CFR 938.13(a)(1). (2)-(4... BMSLCA is not approved to the extent noted in 30 CFR 938.13(a)(5). (13) Section 5.5(b) (52 P.S. 1406.5e(b...

  3. 30 CFR 938.12 - State statutory, regulatory, and proposed program amendment provisions not approved.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... provisions of the proposed program amendment that Pennsylvania submitted on July 29, 1998: (1) Section 5.1(b) (52 P.S. 1406.5a(b)) of BMSLCA is not approved to the extent noted in 30 CFR 938.13(a)(1). (2)-(4... BMSLCA is not approved to the extent noted in 30 CFR 938.13(a)(5). (13) Section 5.5(b) (52 P.S. 1406.5e(b...

  4. 30 CFR 938.12 - State statutory, regulatory, and proposed program amendment provisions not approved.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... provisions of the proposed program amendment that Pennsylvania submitted on July 29, 1998: (1) Section 5.1(b) (52 P.S. 1406.5a(b)) of BMSLCA is not approved to the extent noted in 30 CFR 938.13(a)(1). (2)-(4... BMSLCA is not approved to the extent noted in 30 CFR 938.13(a)(5). (13) Section 5.5(b) (52 P.S. 1406.5e(b...

  5. 30 CFR 938.12 - State statutory, regulatory, and proposed program amendment provisions not approved.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... provisions of the proposed program amendment that Pennsylvania submitted on July 29, 1998: (1) Section 5.1(b) (52 P.S. 1406.5a(b)) of BMSLCA is not approved to the extent noted in 30 CFR 938.13(a)(1). (2)-(4... BMSLCA is not approved to the extent noted in 30 CFR 938.13(a)(5). (13) Section 5.5(b) (52 P.S. 1406.5e(b...

  6. Regulatory withdrawal of medicines marketed with uncertain benefits: the bevacizumab case study.

    PubMed

    Vitry, Agnes; Nguyen, Tuan; Entwistle, Vikky; Roughead, Elizabeth

    2015-01-01

    Withdrawal of conditional regulatory approval or subsidization of new medicines when subsequent evidence does not confirm early trial results may not be well understood or accepted by the public. We present a case study of the US Food and Drug Administration (FDA)'s decision to withdraw the indication of bevacizumab for the treatment of advanced breast cancer and include an analysis of the reactions of stakeholders with a view to identifying opportunities for improving risk management for new medicines with conditional approval or funding. We drew on a range of information sources, including FDA documents, medical journals and media reports, to describe the evidentiary basis of the FDA decisions. We analysed the reactions and perspectives of the stakeholders. In 2008 bevacizumab was granted conditional approval for treatment of advanced breast cancer by the FDA pending submission of supplementary satisfactory evidence. In 2011 the FDA decision to withdraw the indication was met with a hostile reaction from many clinicians and cancer survivors. There were different interpretations of the therapeutic value of bevacizumab with strong beliefs among cancer survivors that the medicine was effective and potential harm was manageable. High expectations of the public may have been encouraged by overly positive media reports and limited understanding by the public of the complexity of the scientific evaluation of new medicines and of the regulatory processes. Improving understanding and acceptance of approval or coverage schemes conditional to evidence development may require the development of risk management plans by regulatory and funding institutions. They may include a range of strategies such as requirements for formal patient acknowledgment of the conditional availability of the medicine, 'black-triangle' equivalent labels that identify full approval is based on pending evidence, and ongoing communication with the media, public and health professionals.

  7. Biosimilars: a regulatory perspective from America

    PubMed Central

    2011-01-01

    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. PMID:21586106

  8. Digital Therapeutics: An Integral Component of Digital Innovation in Drug Development.

    PubMed

    Sverdlov, Oleksandr; van Dam, Joris; Hannesdottir, Kristin; Thornton-Wells, Tricia

    2018-07-01

    Digital therapeutics represent a new treatment modality in which digital systems such as smartphone apps are used as regulatory-approved, prescribed therapeutic interventions to treat medical conditions. In this article we provide a critical overview of the rationale for investing in such novel modalities, including the unmet medical needs addressed by digital therapeutics and the potential for reducing current costs of medical care. We also discuss emerging pathways to regulatory approval and how innovative business models are enabling further growth in the development of digital therapeutics. We conclude by providing some recent examples of digital therapeutics that have gained regulatory approval and highlight opportunities for the near future. © 2018 American Society for Clinical Pharmacology and Therapeutics.

  9. 75 FR 69150 - Self-Regulatory Organizations; The Depository Trust Company; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-10

    ... Process in Providing Trustee Access to the Security Position Report Service November 4, 2010. I.... The current review process to approve a trustee's access to the SPR service for a security is done... a trustee's access to DTC's SPR service for an issue with an automated approval process, DTC will be...

  10. Regulatory issues for computerized electrocardiographic devices.

    PubMed

    Muni, Neal I; Ho, Charles; Mallis, Elias

    2004-01-01

    Computerized electrocardiogram (ECG) devices are regulated in the U.S. by the FDA Center for Devices and Radiological Health (CDRH). This article aims to highlight the salient points of the FDA regulatory review process, including the important distinction between a "tool" claim and a "clinical" claim in the intended use of a computerized ECG device. Specifically, a tool claim relates to the ability of the device to accurately measure a certain ECG parameter, such as T-wave alternans (TWA), while a clinical claim imputes a particular health hazard associated with the identified parameter, such as increased risk of ventricular tachyarrhythmia or sudden death. Given that both types of claims are equally important and receive the same regulatory scrutiny, the manufacturer of a new ECG diagnostic device should consider the distinction and regulatory pathways for approval between the two types of claims discussed in this paper.

  11. Regulatory frameworks for mobile medical applications.

    PubMed

    Censi, Federica; Mattei, Eugenio; Triventi, Michele; Calcagnini, Giovanni

    2015-05-01

    A mobile application (app) is a software program that runs on mobile communication devices such as a smartphone. The concept of a mobile medical app has gained popularity and diffusion but its reference regulatory context has raised discussion and concerns. Theoretically, a mobile app can be developed and uploaded easily by any person or entity. Thus, if an app can have some effects on the health of the users, it is mandatory to identify its reference regulatory context and the applicable prescriptions.

  12. 78 FR 18402 - Self-Regulatory Organizations; New York Stock Exchange LLC; NYSE MKT LLC; Notice of Designation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ...-4 thereunder,\\2\\ proposed rule changes to allow Retail Member Organizations (``RMOs'') to attest...-regulatory organization consents, the Commission shall either approve the proposed rule change, disapprove...-07] Self-Regulatory Organizations; New York Stock Exchange LLC; NYSE MKT LLC; Notice of Designation...

  13. 78 FR 32077 - List of Approved Spent Fuel Storage Casks: MAGNASTOR® System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-29

    ... Fuel Storage Casks: MAGNASTOR[supreg] System AGENCY: Nuclear Regulatory Commission. ACTION: Direct... final rule that would have revised its spent fuel storage regulations to include Amendment No. 3 to... All-purpose Storage (MAGNASTOR[supreg]) System listing within the ``List of Approved Spent Fuel...

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

    NASA Astrophysics Data System (ADS)

    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

  15. Scientific and regulatory reasons for delay and denial of FDA approval of initial applications for new drugs, 2000-2012.

    PubMed

    Sacks, Leonard V; Shamsuddin, Hala H; Yasinskaya, Yuliya I; Bouri, Khaled; Lanthier, Michael L; Sherman, Rachel E

    Some new drug applications fail because of inadequate drug performance and others are not approved because the information submitted to the US Food and Drug Administration (FDA) is unsatisfactory to make that determination. Resubmission of failed applications is costly, delaying marketing approval and the availability of new drugs to patients. To identify the reasons that FDA marketing approval for new drugs was delayed or denied. A retrospective review of FDA documents and extraction of data were performed. We examined all drug applications first submitted to the FDA between 2000 and 2012 for new molecular entities (NMEs), which are active ingredients never before marketed in the United States in any form. Using FDA correspondence and reviews, we investigated the reasons NMEs failed to obtain FDA approval. Reasons for delayed FDA approval or nonapproval of NME applications. Of the 302 identified NME applications, 151 (50%) were approved when first submitted and 222 (73.5%) were ultimately approved. Seventy-one applications required 1 or more resubmissions before approval, with a median delay to approval of 435 days following the first unsuccessful submission. Of the unsuccessful first-time applications, 24 (15.9%) included uncertainties related to dose selection, 20 (13.2%) choice of study end points that failed to adequately reflect a clinically meaningful effect, 20 (13.2%) inconsistent results when different end points were tested, 17 (11.3%) inconsistent results when different trials or study sites were compared, and 20 (13.2%) poor efficacy when compared with the standard of care. The frequency of safety deficiencies was similar among never-approved drugs compared with those with delayed approval (43 of 80 never approved [53.8%] vs 37 of 71 eventually approved [52.1%]; difference, 1.7% [95% CI, -14.86% to 18.05%]; P = .87). However, efficacy deficiencies were significantly more frequent among the never-approved drugs than among those with delayed approvals

  16. 76 FR 40415 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing of Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ... interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's.... \\10\\ 15 U.S.C. 78f(b). \\11\\ 15 U.S.C. 78f(b)(5). B. Self-Regulatory Organization's Statement on Burden...) as to which the self-regulatory organization consents, the Commission will: (A) By order approve or...

  17. 78 FR 937 - Cranberry Pipeline Corporation; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-07

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR13-19-000] Cranberry Pipeline Corporation; Notice of Petition for Rate Approval Take notice that on December 18, 2012, Cranberry Pipeline Corporation (Cranberry) filed pursuant to 284.123 of the Commissions regulations a petition for...

  18. 75 FR 60158 - Self-Regulatory Organizations; The Depository Trust Company; Notice of Filing of a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-29

    ... Process in Providing Trustee Access to the Security Position Report Service September 24, 2010. Pursuant...'') service with an automated approval process. II. Self-Regulatory Organization's Statement of the Purpose of... approve a Trustee's access to the SPR service for a security is done manually, and the process is...

  19. Safety assessment of FDA-approved (orlistat and lorcaserin) anti-obesity medications.

    PubMed

    Halpern, Bruno; Halpern, Alfredo

    2015-02-01

    Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors. This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo. Research, development and approval of new anti-obesity drugs are necessary for improved management of this chronic condition. Orlistat and lorcaserin are two FDA-approved drugs with limited overall efficacy. Nevertheless they are useful weapons for at least some obese individuals. Orlistat has a long and solid safety profile, whereas the safety of lorcaserin is still a matter of debate, mainly due to a lack of long-term data. However, lorcaserin's selective agonism on 5HT2c serotonin receptors diminishes concerns about valvulopathy associated with other serotonin agonists, such as fenfluramine.

  20. 76 FR 72492 - Self-Regulatory Organizations; BATS Exchange, Inc.; BATS Y-Exchange, Inc.; NASDAQ OMX BX, Inc...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-23

    ...-regulatory organization consents, the Commission shall either approve the proposed rule change, disapprove...-NYSEAmex-2011-73; SR- NYSEArca-2011-68; SR-Phlx-2011-129] Self-Regulatory Organizations; BATS Exchange, Inc... PHLX LLC; Notice of a Designation of a Longer Period for Commission Action on Proposed Rule Changes...

  1. US FDA perspective on regulatory issues affecting circulatory assist devices.

    PubMed

    Sapirstein, Wolf; Chen, Eric; Swain, Julie; Zuckerman, Bram

    2006-11-01

    There has been a rapid development in mechanical circulatory support systems in the decade since the US FDA first approved a mechanical device to provide the circulatory support lacking from a failing heart. Devices are presently approved for marketing by the FDA to replace a failing ventricle, the Ventricular Assist Device or the entire heart, Total Artificial Heart. Contemporaneous with, and permitted by, improvement in technology and design, devices have evolved from units located extracorporeally to paracorporeal systems and totally implanted devices. Clinical studies have demonstrated a parallel improvement in the homeostatic adequacy of the circulatory support provided. Thus, while the circulatory support was initially tolerated for short periods to permit recovery of cardiac function, this technology eventually provided effective circulatory support for increasing periods that permitted the FDA to approve devices for bridging patients in end-stage cardiac failure awaiting transplant and eventually a device for destination therapy where patients in end-stage heart failure are not cardiac transplant candidates. The approved devices have relied on displacement pumps that mimic the pulsatility of the physiological system. Accelerated development of more compact devices that rely on alternative pump mechanisms have challenged both the FDA and device manufacturers to assure that the regulatory requirements for safety and effectiveness are met for use of mechanical circulatory support systems in expanded target populations. An FDA regulatory perspective is reviewed of what can be a potentially critical healthcare issue.

  2. Factors related to drug approvals: predictors of outcome?

    PubMed

    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.

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

    PubMed

    2000-01-01

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

  4. Lorcaserin: drug profile and illustrative model of the regulatory challenges of weight-loss drug development.

    PubMed

    Bays, Harold E

    2011-03-01

    Lorcaserin is a selective 5-hydroxytryptamine receptor 2c agonist developed as a weight-loss drug. Phase II and III clinical trials support lorcaserin as not only reducing adiposity (i.e., fat mass), but also as improving the metabolic diseases commonly associated with adiposopathy (i.e., fat dysfunction). At the time of this writing, regulatory processes continue towards evaluating lorcaserin as a potentially marketed weight-loss and weight-maintenance agent. Some of the challenges facing lorcaserin are similar to the difficulties encountered by all investigational weight-loss therapeutic agents, which include evolving paths towards approval. While important for clinicians to understand approval hurdles for all therapeutics, it is especially critical for researchers and developers to grasp the unique regulatory complexities of anti-obesity agents. This article profiles lorcaserin as an illustrative example of general drug development regulatory processes, and specifically details the unique challenge of weight-loss drug development.

  5. European union regulatory developments for new vaccine adjuvants and delivery systems.

    PubMed

    Sesardic, Dorothea; Dobbelaer, Roland

    2004-06-23

    Interest in vaccine adjuvants and new delivery systems has grown rapidly over the past few years. New vaccine candidates have emerged, which, because of their poor immunogenicity, rely on adjuvants to improve their presentation and targeting and to potentiate their protective immune response. Better understandings of the mechanisms of action, together with logistic and economical considerations have resulted in an explosion of technologies. However, there have been few new registered products for human use, and antigens incorporated into immunostimulating reconstituted influenza virosomes have only relatively recently been licensed in European Union (EU) countries. Influenza vaccine, adjuvanted with water in oil emulsion containing squalene (adjuvant MF59C1) is now also approved. Although current EU regulations focus on traditional adjuvants, notably aluminium and calcium salts, advances have been made in regulatory considerations. The European agency for the evaluation of medicinal products, through its working parties, is actively drafting guidance on requirements for the evaluation of new adjuvants in vaccines. This paper summarises the new developments in EU regulatory aspects relevant to adjuvant quality at development stages, during the manufacturing process, and at the final bulk stage of adjuvant with antigen, and also summarises regulatory expectation regarding safety at pre-clinical and clinical stages. The paper highlights the regulatory concerns and existing bottlenecks that have led to slow approval of new technologies.

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

    PubMed

    Shimazawa, Rumiko; Ikeda, Masayuki

    2016-03-01

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

  7. Side effects of cytokines approved for therapy.

    PubMed

    Baldo, Brian A

    2014-11-01

    Cytokines, currently known to be more than 130 in number, are small MW (<30 kDa) key signaling proteins that modulate cellular activities in immunity, infection, inflammation and malignancy. Key to understanding their function is recognition of their pleiotropism and often overlapping and functional redundancies. Classified here into 9 main families, most of the 20 approved cytokine preparations (18 different cytokines; 3 pegylated), all in recombinant human (rh) form, are grouped in the hematopoietic growth factor, interferon, platelet-derived growth factor (PDGF) and transforming growth factor β (TGFβ) families. In the hematopoietin family, approved cytokines are aldesleukin (rhIL-2), oprelvekin (rhIL-11), filgrastim and tbo-filgrastim (rhG-CSF), sargramostim (rhGM-CSF), metreleptin (rh-leptin) and the rh-erythropoietins, epoetin and darbepoietin alfa. Anakinra, a recombinant receptor antagonist for IL-1, is in the IL-1 family; recombinant interferons alfa-1, alfa-2, beta-1 and gamma-1 make up the interferon family; palifermin (rhKGF) and becaplermin (rhPDGF) are in the PDGF family; and rhBMP-2 and rhBMP-7 represent the TGFβ family. The main physicochemical features, FDA-approved indications, modes of action and side effects of these approved cytokines are presented. Underlying each adverse events profile is their pleiotropism, potency and capacity to release other cytokines producing cytokine 'cocktails'. Side effects, some serious, occur despite cytokines being endogenous proteins, and this therefore demands caution in attempts to introduce individual members into the clinic. This caution is reflected in the relatively small number of cytokines currently approved by regulatory agencies and by the fact that 14 of the FDA-approved preparations carry warnings, with 10 being black box warnings.

  8. Drug Lag and Key Regulatory Barriers in the Emerging Markets

    PubMed Central

    Wileman, Harriet; Mishra, Arun

    2010-01-01

    There have been numerous investigations targeted at identifying whether a drug lag exists in the mature markets of the US, EU and Japan. This work focuses on the emerging markets because of the potential they hold for the future of the pharmaceutical industry as a consequence of rapid economic and political development. The aims of this work are to ascertain whether a drug lag exists in the emerging markets and how it has changed over time from the 1960s to the 2000s. It will also highlight key regulatory barriers which may contribute to drug lag. The date of the marketing authorisation (MA) approval by the US Food and Drug Administration (FDA) was used as a reference point. A comparison against the company database regarding emerging market specific approval enabled the difference in time and thus the drug lag for that particular market to be calculated. 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. PMID:21829782

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

    PubMed

    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.

  10. 78 FR 11638 - NorthWestern Corporation; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-19

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR13-27-000] NorthWestern Corporation; Notice of Petition for Rate Approval Take notice that on January 31, 2013, NorthWestern Corporation (NorthWestern) filed a Rate Election pursuant to 284.123(b)(1) of the Commissions regulations...

  11. 76 FR 34975 - Atmos Pipeline-Texas; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR11-112-000] Atmos Pipeline-Texas; Notice of Petition for Rate Approval Take notice that on June 6, 2011, Atmos Pipeline-Texas (APT... transportation service. APT states the rate election reflects its cost-based transportation rates on file with...

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

    PubMed

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

    2017-01-01

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

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

    PubMed

    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.

  14. Trainees' Perceived Knowledge Gain Unrelated to the Training Domain: The Joint Action of Impression Management and Motives

    ERIC Educational Resources Information Center

    Chiaburu, Dan S.; Huang, Jason L.; Hutchins, Holly M.; Gardner, Richard G.

    2014-01-01

    Trainees' knowledge gains represent an important outcome in human resource development. In this research, we tested a model examining the joint influence of social desirability (impression management, self-deception) and motives (need for power, need for approval) on trainees' self-reported knowledge gain. We conducted a study with…

  15. Orthopaedic Device Approval Through the Premarket Approval Process: A Financial Feasibility Analysis for a Single Center.

    PubMed

    Yang, Brian W; Iorio, Matthew L; Day, Charles S

    2017-03-15

    The 2 main routes of medical device approval through the U.S. Food and Drug Administration are the premarket approval (PMA) process, which requires clinical trials, and the 510(k) premarket notification, which exempts devices from clinical trials if they are substantially equivalent to an existing device. Recently, there has been growing concern regarding the safety of devices approved through the 510(k) premarket notification. The PMA process decreases the potential for device recall; however, it is substantially more costly and time-consuming. Investors and medical device companies are only willing to invest in devices if they can expect to recoup their investment within a timeline of roughly 7 years. Our study utilizes financial modeling to assess the financial feasibility of approving various orthopaedic medical devices through the 510(k) and PMA processes. The expected time to recoup investment through the 510(k) process ranged from 0.585 years to 7.715 years, with an average time of 2.4 years; the expected time to recoup investment through the PMA route ranged from 2.9 years to 24.5 years, with an average time of 8.5 years. Six of the 13 orthopaedic device systems that we analyzed would require longer than our 7-year benchmark to recoup the investment costs of the PMA process. With the 510(k) premarket notification, only 1 device system would take longer than 7 years to recoup its investment costs. Although the 510(k) premarket notification has demonstrated safety concerns, broad requirements for PMA authorization may limit device innovation for less-prevalent orthopaedic conditions. As a result, new approval frameworks may be beneficial. Our report demonstrates how current regulatory policies can potentially influence orthopaedic device innovation.

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

    PubMed Central

    Sinebo, Woldeyesus; Maredia, Karim

    2016-01-01

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

  17. 77 FR 22569 - NorthWestern Corporation; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-16

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR12-20-000] NorthWestern Corporation; Notice of Petition for Rate Approval Take notice that on April 2, 2012, NorthWestern Corporation (NorthWestern) filed a Rate Election pursuant to 284.123(b)(1) of the Commissions regulations and to...

  18. 77 FR 48976 - NorthWestern Corporation; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR12-32-000] NorthWestern Corporation; Notice of Petition for Rate Approval Take notice that on July 31, 2012, NorthWestern Corporation (NorthWestern) filed a Rate Election pursuant to 284.123(b)(1) of the Commissions regulations and to...

  19. 78 FR 16667 - Peoples TWP LLC; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-18

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR13-42-000] Peoples TWP LLC; Notice of Petition for Rate Approval Take notice that on March 1, 2013, Peoples TWP LLC (Peoples TWP... rates that are the same as those contained in Peoples TWP's Rate Schedule FTS--Field Transportation...

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

    PubMed

    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.

  1. 18 CFR 131.20 - Application for approval of transfer of license.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... REGULATORY POLICIES ACT OF 1978 FORMS § 131.20 Application for approval of transfer of license. (See §§ 9.1... Commission certified copies of the instruments of such conveyance (see par. 6 of this form). The transferor shall at the same time make payment of annual charges to the date of the conveyance (see par. 6 of this...

  2. 78 FR 1854 - Minnesota Energy Resources Corporation; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-09

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR13-21-000] Minnesota..., Minnesota Energy Resources Corporation (MERC) filed a rate election pursuant to section 284.123(b)(1) of the... that conform to the recently revised rates approved by the Minnesota Public Utilities Commission, as...

  3. Gaining and Maintaining Cyberspace Superiority: A Quest for the Holy Grail

    DTIC Science & Technology

    2009-06-01

    GAINING AND MAINTAINING CYBERSPACE SUPERIORITY: QUEST FOR A HOLY GRAIL? BY MERNA H. H. HSU A THESIS PRESENTED TO THE FACULTY OF THE SCHOOL...especially those at the foundation of the militarys decision making for operations and requirements. This thesis examined whether cyberspace can be...APPROVAL The undersigned certify that this thesis meets masters-level standards of research

  4. How to Get JDRP Approval of Career Education Activities.

    ERIC Educational Resources Information Center

    Hamilton, Jack A.

    The purpose of this monograph is to aid practitioners in gaining federal Joint Dissemination Review Panel (JDRP) approval of career education projects. It helps them understand the importance of designing and implementing a sound evaluation from the early stages of the program, alerts them to common errors or omissions that weaken or destroy…

  5. 75 FR 64771 - Self-Regulatory Organizations; Order Approving Minor Rule Violation Plan for BATS Y-Exchange, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-20

    ... 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... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63113; File No. 4-616] Self-Regulatory...

  6. Miracle drug: Brazil approves never-tested cancer medicine.

    PubMed

    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.

  7. 77 FR 14861 - Approval and Promulgation of Implementation Plans; State of Nevada; Revised Format for Materials...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-13

    ...EPA is revising the format for materials submitted by the State of Nevada that are incorporated by reference (IBR) into the Nevada State Implementation Plan (SIP). The regulations affected by this format change have all been previously submitted by the State of Nevada and approved by EPA. This format revision will primarily affect the ``Identification of plan'' section, as well as the format of the SIP materials that will be available for public inspection at the National Archives and Records Administration (NARA), the Air and Radiation Docket and Information Center located at EPA Headquarters in Washington, DC, and the EPA Regional Office. EPA is also adding a table in the ``Identification of plan'' section which summarizes the approval actions that EPA has taken on the non-regulatory and quasi-regulatory portions of the Nevada SIP.

  8. A look backward and forward in the regulatory and treatment history of multiple myeloma: Approval of novel-novel agents, new drug development, and longer patient survival.

    PubMed

    Kazandjian, Dickran; Landgren, Ola

    2016-12-01

    The past decade has seen significant advances in our understanding and treatment of multiple myeloma (MM) and its precursor diseases. These advances include gains in knowledge of the underlying pathobiology including molecular and cellular prognostic factors for disease progression. In parallel we have witnessed the availability of novel therapeutics. Together these advances have translated into improvements in long-term clinical benefit and survival in MM. Indeed, it has been shown that patients diagnosed in the last decade have experienced almost doubling of median survival time. We aim to review and give further insight into drug development and novel drug approvals that have revolutionized the treatment of MM. Published by Elsevier Inc.

  9. Individual differences in regulatory focus predict neural response to reward.

    PubMed

    Scult, Matthew A; Knodt, Annchen R; Hanson, Jamie L; Ryoo, Minyoung; Adcock, R Alison; Hariri, Ahmad R; Strauman, Timothy J

    2017-08-01

    Although goal pursuit is related to both functioning of the brain's reward circuits and psychological factors, the literatures surrounding these concepts have often been separate. Here, we use the psychological construct of regulatory focus to investigate individual differences in neural response to reward. Regulatory focus theory proposes two motivational orientations for personal goal pursuit: (1) promotion, associated with sensitivity to potential gain, and (2) prevention, associated with sensitivity to potential loss. The monetary incentive delay task was used to manipulate reward circuit function, along with instructional framing corresponding to promotion and prevention in a within-subject design. We observed that the more promotion oriented an individual was, the lower their ventral striatum response to gain cues. Follow-up analyses revealed that greater promotion orientation was associated with decreased ventral striatum response even to no-value cues, suggesting that promotion orientation may be associated with relatively hypoactive reward system function. The findings are also likely to represent an interaction between the cognitive and motivational characteristics of the promotion system with the task demands. Prevention orientation did not correlate with ventral striatum response to gain cues, supporting the discriminant validity of regulatory focus theory. The results highlight a dynamic association between individual differences in self-regulation and reward system function.

  10. Regulatory and clinical considerations for biosimilar oncology drugs

    PubMed Central

    Bennett, Charles L; Chen, Brian; Hermanson, Terhi; Wyatt, Michael D; Schulz, Richard M; Georgantopoulos, Peter; Kessler, Samuel; Raisch, Dennis W; Qureshi, Zaina P; Lu, Z Kevin; Love, Bryan L; Noxon, Virginia; Bobolts, Laura; Armitage, Melissa; Bian, John; Ray, Paul; Ablin, Richard J; Hrushesky, William J; Macdougall, Iain C; Sartor, Oliver; Armitage, James O

    2015-01-01

    Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents—molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs—provide opportunities both to improve healthcare access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns. PMID:25456378

  11. Food irradiation—US regulatory considerations

    NASA Astrophysics Data System (ADS)

    Morehouse, Kim M.

    2002-03-01

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

  12. 76 FR 70795 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice and Order Granting Accelerated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-15

    ...-Regulatory Organizations; New York Stock Exchange LLC; Notice and Order Granting Accelerated Approval to..., New York Stock Exchange LLC (``NYSE'' or ``Exchange'') filed with the Securities and Exchange... 70796

  13. Isolation of CD4+CD25+ regulatory T cells for clinical trials.

    PubMed

    Hoffmann, Petra; Boeld, Tina J; Eder, Ruediger; Albrecht, Julia; Doser, Kristina; Piseshka, Biserka; Dada, Ashraf; Niemand, Claudia; Assenmacher, Mario; Orsó, Evelyn; Andreesen, Reinhard; Holler, Ernst; Edinger, Matthias

    2006-03-01

    The adoptive transfer of donor CD4+CD25+ regulatory T cells has been shown to protect from lethal graft-versus-host disease after allogeneic bone marrow transplantation in murine disease models. Efficient isolation strategies that comply with good manufacturing practice (GMP) guidelines are prerequisites for the clinical application of human CD4+CD25+ regulatory T cells. Here we describe the isolation of CD4+CD25+ T cells with regulatory function from standard leukapheresis products by using a 2-step magnetic cell-separation protocol performed under GMP conditions. The generated cell products contained on average 49.5% CD4+CD25high T cells that phenotypically and functionally represented natural CD4+CD25+ regulatory T cells and showed a suppressive activity comparable to that of CD4+CD25+ regulatory T-cell preparations purified by non-GMP-approved fluorescence-activated cell sorting.

  14. 76 FR 20066 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-11

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64189; File No. SR-CBOE-2011-008] Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting Approval of Proposed... Chicago Board Options Exchange, Incorporated (``CBOE'' or ``Exchange'') filed with the Securities and...

  15. 77 FR 70432 - Washington Gas Light Company; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-26

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket Nos. PR13-6-000; PR13-7-000] Washington Gas Light Company; Notice of Petition for Rate Approval Take notice that on November 9, 2012, Washington Gas Light Company (Washington Gas) filed its Lost and unaccounted-for Gas (LAUF) as provided for...

  16. 34 CFR 97.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... possible long-range effects of applying knowledge gained in the research (for example, the possible effects... 34 Education 1 2010-07-01 2010-07-01 false Criteria for IRB approval of research. 97.111 Section... Federal Policy for the Protection of Human Subjects (Basic ED Policy for Protection of Human Research...

  17. 40 CFR 26.1111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Criteria for IRB approval of research...

  18. 40 CFR 26.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... possible long-range effects of applying knowledge gained in the research (for example, the possible effects... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Criteria for IRB approval of research... HUMAN SUBJECTS Basic EPA Policy for Protection of Subjects in Human Research Conducted or Supported by...

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

    PubMed

    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.

  20. 76 FR 37867 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  1. The regulatory sciences for stem cell-based medicinal products.

    PubMed

    Yuan, Bao-Zhu; Wang, Junzhi

    2014-06-01

    Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced. More relevantly, the stem cell regulatory sciences need to be established or improved to more effectively evaluate quality, safety and efficacy of stem cell products, and for building up the appropriate regulatory framework. In this review, we summarize some new achievements in stem cell studies, especially the preclinical and clinical studies, the existing regulations, and the associated challenges, and we then propose some considerations for improving stem cell regulatory sciences with a goal of promoting the steadfast growth of the well-regulated stem cell therapies abreast of evolvement of stem cell sciences and technologies.

  2. 75 FR 29787 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting Accelerated Approval of Proposed Rule Change To Permit $1 Strikes for Options on Trust Issued Receipts May 20, 2010. I. Introduction On April 13, 2010, the Chicago Board Options Exchange, Incorporated (``CBOE'' or ``Exchange...

  3. 75 FR 73155 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-29

    ...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting Approval of Proposed Rule Change To Amend Certain Rules Pertaining to Credit Options November 19, 2010. I. Introduction On September 20, 2010, the Chicago Board Options Exchange, Incorporated (``CBOE'' or ``Exchange'') filed with...

  4. 45 CFR 46.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... applying knowledge gained in the research (for example, the possible effects of the research on public... 45 Public Welfare 1 2010-10-01 2010-10-01 false Criteria for IRB approval of research. 46.111... HUMAN SUBJECTS Basic HHS Policy for Protection of Human Research Subjects § 46.111 Criteria for IRB...

  5. 21 CFR 56.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among... included in the study to protect the rights and welfare of these subjects. (c) In order to approve research...

  6. 10 CFR 745.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among... 10 Energy 4 2010-01-01 2010-01-01 false Criteria for IRB approval of research. 745.111 Section 745...

  7. 32 CFR 219.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks... 32 National Defense 2 2010-07-01 2010-07-01 false Criteria for IRB approval of research. 219.111...

  8. 45 CFR 690.111 - Criteria for IRB approval of research.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that... 45 Public Welfare 3 2010-10-01 2010-10-01 false Criteria for IRB approval of research. 690.111...

  9. 75 FR 41855 - Enogex L.L.C.; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  10. Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Wink, Logan K.; Adams, Ryan; Pedapati, Ernest V.; Dominick, Kelli C.; Fox, Emma; Buck, Catherine; Erickson, Craig A.

    2017-01-01

    Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming increasingly common, placing individuals at risk for antipsychotic-induced weight gain and associated complications. Metformin hydrochloride, a biguanide medication FDA-approved for treatment of type-2 diabetes in youth, may hold promise for treatment of…

  11. Sequence information gain based motif analysis.

    PubMed

    Maynou, Joan; Pairó, Erola; Marco, Santiago; Perera, Alexandre

    2015-11-09

    The detection of regulatory regions in candidate sequences is essential for the understanding of the regulation of a particular gene and the mechanisms involved. This paper proposes a novel methodology based on information theoretic metrics for finding regulatory sequences in promoter regions. This methodology (SIGMA) has been tested on genomic sequence data for Homo sapiens and Mus musculus. SIGMA has been compared with different publicly available alternatives for motif detection, such as MEME/MAST, Biostrings (Bioconductor package), MotifRegressor, and previous work such Qresiduals projections or information theoretic based detectors. Comparative results, in the form of Receiver Operating Characteristic curves, show how, in 70% of the studied Transcription Factor Binding Sites, the SIGMA detector has a better performance and behaves more robustly than the methods compared, while having a similar computational time. The performance of SIGMA can be explained by its parametric simplicity in the modelling of the non-linear co-variability in the binding motif positions. Sequence Information Gain based Motif Analysis is a generalisation of a non-linear model of the cis-regulatory sequences detection based on Information Theory. This generalisation allows us to detect transcription factor binding sites with maximum performance disregarding the covariability observed in the positions of the training set of sequences. SIGMA is freely available to the public at http://b2slab.upc.edu.

  12. 76 FR 53529 - Agency Information Collection Activities: Requests for Comments; Clearance of Renewed Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-26

    ... intention to request the Office of Management and Budget (OMB) approval for to renew an information... collected allows the FAA to evaluate its certification standards, maintenance programs, and regulatory... of Management and Budget. Comments should be addressed to the attention of the Desk Officer...

  13. 30 CFR 916.12 - State regulatory program and proposed program amendment provisions not approved.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... approved. (a) The following provisions of the Kansas Administrative Regulations (K.A.R.) as submitted on April 23, 1986, and January 26, 1988, are disapproved: Paragraphs (c) and (d) of K.A.R. 47-9-1 insofar...

  14. 30 CFR 916.12 - State regulatory program and proposed program amendment provisions not approved.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... approved. (a) The following provisions of the Kansas Administrative Regulations (K.A.R.) as submitted on April 23, 1986, and January 26, 1988, are disapproved: Paragraphs (c) and (d) of K.A.R. 47-9-1 insofar...

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

    PubMed

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

    2014-01-01

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

  16. Integration of new technology into clinical practice after FDA approval.

    PubMed

    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.

  17. 76 FR 47280 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-04

    ...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting Approval of Proposed Rule Change To List and Trade Single Stock Dividend Options July 29, 2011. On May 31, 2011, the Chicago Board Options Exchange, Incorporated (``Exchange'' or ``CBOE'') filed with the Securities and Exchange...

  18. 77 FR 528 - Self-Regulatory Organizations; The National Securities Clearing Corporation; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-05

    ...-Regulatory Organizations; The National Securities Clearing Corporation; Order Granting Approval of a Proposed Rule Change To Amend Rules Relating To the Creation of a Service To Provide Post-Trade Information... trading activity of their organizations, their correspondent firms, or both through review of post-trade...

  19. 77 FR 35448 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67152; File No. SR-CBOE-2012-013] Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting Approval of a Proposed Rule Change To Adopt Self-Trade Prevention Modifiers on the CBOE Stock Exchange June 7, 2012. I...

  20. The European Regulatory Environment of RNA-Based Vaccines.

    PubMed

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

    2017-01-01

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

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

    PubMed

    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.

  2. 76 FR 47085 - Effective Date of Requirement for Premarket Approval for a Pacemaker Programmer

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-04

    .... FDA-2011-N-0526] Effective Date of Requirement for Premarket Approval for a Pacemaker Programmer... programmers. The agency is also summarizing its proposed findings regarding the degree of risk of illness or.... Background--Regulatory Authorities The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the...

  3. Overview of the Regulatory Oversight Implemented by the French Regulatory Authorities for the Clinical Investigation of Gene Therapy and Cell Therapy Products.

    PubMed

    Lucas-Samuel, Sophie; Ferry, Nicolas; Trouvin, Jean-Hugues

    2015-01-01

    Advanced therapy medicinal products, a new class of products with promising therapeutic effects, have been classified as medicinal products and as such should be developed according to a well-structured development plan, to establish their quality, safety and efficacy profile and conclude, at the time of the marketing authorisation evaluation, on a positive risk/benefit balance for patients. An important part of this development plan is achieved through clinical trials, which have also to be approved according to a well-established regulatory process, prior any initiation. This chapter is dedicated to describe the regulatory pathway to be followed in France, before initiating any clinical trial with those investigational advanced therapy medicinal products. In France, to get the final authorisation to initiate a clinical trial, the legislation imposes to run in parallel two independent but complementary authorisation procedures. The first procedure is aimed at assessing the ethical aspect of the biomedical research, while the second has to review the safety and regulatory aspects. A third procedure has to be envisaged where in case the investigational product consists or contains a genetically modified organism. The French system herein described is in line with the EU regulation on clinical trial and follows the respective deadlines for granting the final approval. The complexity of the procedure is in fact more due to the complexity of the products and protocols to be assessed than to the procedure itself which is now very close to the well-known procedure applied routinely for more conventional chemical or biological candidate medicinal products.

  4. 77 FR 24585 - List of Approved Spent Fuel Storage Casks: HI-STORM 100, Revision 8

    Federal Register 2010, 2011, 2012, 2013, 2014

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-13

    ... Fuel Storage Casks: NUHOMS[supreg] HD System Revision 1 AGENCY: Nuclear Regulatory Commission. ACTION... amend its spent fuel storage cask regulations by revising the Transnuclear, Inc. (TN) NUHOMS[supreg] HD System listing within the ``List of Approved Spent Fuel Storage Casks'' to include Amendment No. 1 to...

  6. 76 FR 23339 - Notice of Issuance of License Amendment Regarding Decommission Plan Approval; University of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-26

    ... NUCLEAR REGULATORY COMMISSION [Docket No. 50-113; NRC-2009-0549] Notice of Issuance of License Amendment Regarding Decommission Plan Approval; University of Arizona Research Reactor The U.S. Nuclear... located within the University of Arizona Nuclear Reactor Laboratory (NRL) on the 325-acre campus of the...

  7. 76 FR 46322 - Agency Information Collection Activities Under OMB Review; Renewal of a Currently Approved...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  8. 77 FR 3828 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... Organizations; The Options Clearing Corporation; Order Granting Approval of Accelerated Delivery of Supplement to the Options Disclosure Document Reflecting Certain Changes to Disclosure Regarding Relative Performance Options January 19, 2012. On August 15, 2011, The Options Clearing Corporation (``OCC'') submitted...

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

    PubMed

    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.

  10. 76 FR 13442 - Joint Industry Plan; Order Approving Amendment No. 25 to the Joint Self-Regulatory Organization...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  11. FDA's Flexibility in Subpart H Approvals: Assessing Quantum of Effectiveness Evidence.

    PubMed

    Sasinowski, Frank J; Varond, Alexander J

    2016-08-01

    This article examines the strength of scientific and clinical evidence for FDA's nineteen non-AIDS, non-cancer Subpart H approval determinations over the Accelerated Approval program's twenty-four year existence. The authors researched the bases for FDA's determinations when an unvalidated surrogate or intermediate clinical endpoint is "reasonably likely to predict clinical benefit." The four key factors set forth in FDA's "Guidance for Industry, Expedited Programs for Serious Conditions - Drugs and Biologics" were applied to past Subpart H approvals. For the nineteen precedents, the authors found wide variances between the quantum and quality of evidence on each of the four factors, indicating that a lack of evidence on any single factor was not disqualifying in and of itself. The results of this study, therefore, show that FDA exercises extraordinarily more regulatory flexibility than either FDA's foundational statutes or even FDA' s most recent 2014 Expedited Programs Guidance explicitly express. Given recent legislative exhortations and the increasing promise of personalized medicine and translational sciences, the authors conclude that Subpart H should be further explored and utilized. The authors provide a detailed analysis of the orecedents established in the nineteen approvals.

  12. 77 FR 24380 - Treatment of Gain Recognized With Respect to Stock in Certain Foreign Corporations Upon...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-24

    ... Services and Enforcement. Approved: April 13, 2012. Emily S. McMahon, Acting Assistant Secretary of the... been determined that 5 U.S.C. 553(b) and (d) do not apply to these regulations. Pursuant to the Regulatory Flexibility Act (5 U.S.C. 601 et seq.), it is hereby certified that this rule will not have a...

  13. The New Drug Conditional Approval Process in China: Challenges and Opportunities.

    PubMed

    Yao, Xuefang; Ding, Jinxi; Liu, Yingfang; Li, Penghui

    2017-05-01

    Our aim was to characterize the newly established new drug conditional approval process in China and discuss the challenges and opportunities with respect to new drug research and development and registration. We examined the new approval program through literature review, law analysis, and data analysis. Data were derived from published materials, such as journal articles, government publications, press releases, and news articles, along with statistical data from INSIGHT-China Pharma Databases, the China Food and Drug Administration website, the Center for Drug Evaluation website, the US Food and Drug Administration website, and search results published by Google. Currently, there is a large backlog of New Drug Applications in China, mainly because of the prolonged review time at the China Food and Drug Administration, resulting in a lag in drug approvals. In 2015, the Chinese government implemented the drug review and registration system reform and tackled this issue through various approaches, such as setting up a drug review fee system, adjusting the drug registration classification, and establishing innovative review pathways, including the conditional approval process. In Europe and the United States, programs comparable to the conditional approval program in China have been well developed. The conditional approval program recently established in China is an expedited new drug approval process that is expected to affect new drug development at home and abroad and profoundly influence the public health and the pharmaceutical industry in China. Like any program in its initial stage, the conditional approval program is facing several challenges, including setting up a robust system, formatting new drug clinical research requirements, and improving the regulatory agency's function for drug review and approval. The program is expected to evolve and improve as part of the government mandate of the drug registration system reform. Copyright © 2017 Elsevier HS

  14. Is the GAIN Act a turning point in new antibiotic discovery?

    PubMed

    Brown, Eric D

    2013-03-01

    The United States GAIN (Generating Antibiotic Incentives Now) Act is a call to action for new antibiotic discovery and development that arises from a ground swell of concern over declining activity in this therapeutic area in the pharmaceutical sector. The GAIN Act aims to provide economic incentives for antibiotic drug discovery in the form of market exclusivity and accelerated drug approval processes. The legislation comes on the heels of nearly two decades of failure using the tools of modern drug discovery to find new antibiotic drugs. The lessons of failure are examined herein as are the prospects for a renewed effort in antibiotic drug discovery and development stimulated by new investments in both the public and private sector.

  15. 78 FR 6378 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ... Organizations; The Options Clearing Corporation; Order Approving Proposed Rule Change To Accommodate Certain Physically- Settled Options on U.S. Treasury Securities January 23, 2013. I. Introduction On November 30, 2012, The Options Clearing Corporation (``OCC'') filed with the Securities and Exchange Commission...

  16. 75 FR 30451 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Granting Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-01

    ... May 14, 2010. The ODD currently contains general disclosures on the characteristics and risks of...-linked securities. Accordingly, the ODD disclosure only covers the characteristics and risks of options...; Order Granting Approval of Accelerated Delivery of Supplement to the Options Disclosure Document...

  17. 77 FR 53241 - Self-Regulatory Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-31

    ... Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change Relating to the Auction Process Under Options Clearing Corporation Rule 1104 August 27, 2012. I. Introduction On July 3, 2012, the Options Clearing Corporation (``OCC'') filed with the Securities and Exchange Commission (``Commission...

  18. 77 FR 43881 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting Approval of Proposed Rule Change To List and Trade CBOE S&P 500 AM/PM Basis Options July 20, 2012. I. Introduction On May 23, 2012, the Chicago Board Options Exchange, Incorporated (``Exchange'' or ``CBOE'') filed with the...

  19. Humanitarian Use Device and Humanitarian Device Exemption regulatory programs: pros and cons.

    PubMed

    Bernad, Daniel Maxwell

    2009-03-01

    The US FDA established the Humanitarian Use Device (HUD) and Humanitarian Device Exemption (HDE) program to encourage medical device firms to address rare diseases. Despite being in existence for over a decade, there has only been one peer-reviewed publication examining this field. The objective of this report is to investigate how the HUD/HDE program differs from the standard regulatory system, discuss its potential advantages and disadvantages, and to speculate which humanitarian devices will be brought to market within the next 5 years. A total of 40 semistructured interviews with stakeholders, representing approximately half (n = 20, 49%) of the firms that have successfully obtained HDE-approved products, were performed in order to acquire the primary data for this paper. There appear to be short-term gains and long-term drains associated with launching humanitarian devices to market. This report aims to provide sponsors with information that may allow them to make better decisions during their product development of humanitarian devices and may, hopefully, also play a role in encouraging other sponsors to take the necessary steps forward in helping to find treatments for patients with rare diseases.

  20. Industry funding of the FDA: effects of PDUFA on approval times and withdrawal rates.

    PubMed

    Berndt, Ernst R; Gottschalk, Adrian H B; Philipson, Tomas J; Strobeck, Matthew W

    2005-07-01

    The development of new therapies is a crucial component of efforts to improve healthcare. Because drug development and FDA regulatory review have historically been lengthy and costly processes, the US Congress passed a series of legislative acts, beginning in 1992, known collectively as the Prescription Drug User Fee Acts (PDUFA), which sought to expedite the FDA drug-review process. Here, we review data on drug approvals and drug-approval times, both as a whole and by therapeutic class, which demonstrate that implementation of the PDUFAs led to substantial incremental reductions in approval times beyond what would have been observed in the absence of these legislative acts. In addition, our preliminary examination of the trends in the number of new molecular entity withdrawals, frequently used as a proxy to assess the FDA's safety record, suggests that the proportion of approvals ultimately leading to safety withdrawals prior to PDUFA and during PDUFA I and II were not statistically different.

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