Public-private partnerships as driving forces in the quest for innovative medicines

PubMed Central

2013-01-01

Background Despite progress in translational research, we are still falling short in developing the innovative medicines required to address major public health needs. Furthermore, the failure rate, time, and cost required for registration of a new drug are pushing the economics of the industry to the breaking point. New models of drug development based on collaborative endeavours are badly needed to improve this dire situation. Findings In 2004, the US Food and Drug Administration (FDA) introduced the Critical Path Initiative with the intent of modernizing drug development by implementing public-private partnerships (PPP) to share data, expertise, and resources. In response to FDA’s initiative, in the following year the non-profit Critical Path Institute (C-Path) was formed. At the same time, the National Institutes of Health (NIH) Public-Private Partnership program was established. In Europe, the Innovative Medicines Initiative (IMI) supported jointly by the European Union and the European Federation of Pharmaceutical Industries and Associations was launched in 2008. These independent efforts have a common long-term objective, namely to facilitate the emergence of innovative medicines by developing new tools for drug discovery, new indicators for drug efficacy or safety, and new approaches for patient stratification. Herein, we present evidence that PPP already exert a positive impact on the drug development process. Conclusions Public-private partnerships represent attractive means to leverage resources dispersed across industry, academia, and voluntary health organizations in order to address multiple challenges of drug development in an era of constrained resources and increased regulatory pressure. PMID:23369569

Precompetitive Data Sharing as a Catalyst to Address Unmet Needs in Parkinson’s Disease 1

PubMed Central

Stephenson, Diane; Hu, Michele T.; Romero, Klaus; Breen, Kieran; Burn, David; Ben-Shlomo, Yoav; Bhattaram, Atul; Isaac, Maria; Venuto, Charles; Kubota, Ken; Little, Max A.; Friend, Stephen; Lovestone, Simon; Morris, Huw R.; Grosset, Donald; Sutherland, Margaret; Gallacher, John; Williams-Gray, Caroline; Bain, Lisa J.; Avilés, Enrique; Marek, Ken; Toga, Arthur W.; Stark, Yafit; Forrest Gordon, Mark; Ford, Steve

2015-01-01

Abstract Parkinson’s disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson’s UK and co-organized by Critical Path Institute’s (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson’s disease. PMID:26406139

77 FR 51814 - Draft Guidance for Industry on Generic Drug User Fee Amendments of 2012: Questions and Answers...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-27

... costs to industry. GDUFA enables FDA to assess user fees to support critical and measurable enhancements... critical and measurable enhancements to FDA's generic drugs program. GDUFA establishes fees for abbreviated... current thinking on generic drug user fee amendments of 2012. It does not create or confer any rights for...

78 FR 55261 - Draft Guidance for Industry on Generic Drug User Fee Amendments of 2012: Questions and Answers...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-10

... public and reduce costs to industry. GDUFA enables FDA to assess user fees to support critical and... assess user fees to support critical and measurable enhancements to FDA's generic drugs program. GDUFA...). The draft guidance, when finalized, will represent the Agency's current thinking on ``Generic Drug...

Biologics as countermeasures for acute radiation syndrome: where are we now?

PubMed

Singh, Vijay K; Romaine, Patricia L P; Newman, Victoria L

2015-04-01

Despite significant scientific advances toward the development of a safe, nontoxic and effective radiation countermeasure for acute radiation syndrome (ARS) over the past six decades, no drug has been approved by the US FDA. Several biologics are currently under development as radiation countermeasures for ARS, of which three have received FDA Investigational New Drug (IND) status for clinical investigation. Presently, two of these agents, entolimod (CBLB502) and HemaMax (recombinant human IL-12) are progressing with large animal studies and clinical trials. Neupogen (G-CSF, filgrastim) has recently been recommended for approval by an FDA Advisory Committee. Filgrastim, GM-CSF (Leukine, sargramostim), and PEGylated G-CSF (Neulasta) have high potential and well-documented therapeutic effects in countering myelosuppression and may receive full licensing approval by the FDA in the future. The former two biologics are available in the US Strategic National Stockpile (SNS) for use in the event of nuclear or radiological emergency. The Emergency Use Authorization (EAU) application for entolimod may be filed soon with the FDA. Biologics are attractive agents that are progressing along the path for FDA approval, to fill the unmet need for ARS countermeasures.

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.

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

Rational Selection, Criticality Assessment, and Tiering of Quality Attributes and Test Methods for Analytical Similarity Evaluation of Biosimilars.

PubMed

Vandekerckhove, Kristof; Seidl, Andreas; Gutka, Hiten; Kumar, Manish; Gratzl, Gyöngyi; Keire, David; Coffey, Todd; Kuehne, Henriette

2018-05-10

Leading regulatory agencies recommend biosimilar assessment to proceed in a stepwise fashion, starting with a detailed analytical comparison of the structural and functional properties of the proposed biosimilar and reference product. The degree of analytical similarity determines the degree of residual uncertainty that must be addressed through downstream in vivo studies. Substantive evidence of similarity from comprehensive analytical testing may justify a targeted clinical development plan, and thus enable a shorter path to licensing. The importance of a careful design of the analytical similarity study program therefore should not be underestimated. Designing a state-of-the-art analytical similarity study meeting current regulatory requirements in regions such as the USA and EU requires a methodical approach, consisting of specific steps that far precede the work on the actual analytical study protocol. This white paper discusses scientific and methodological considerations on the process of attribute and test method selection, criticality assessment, and subsequent assignment of analytical measures to US FDA's three tiers of analytical similarity assessment. Case examples of selection of critical quality attributes and analytical methods for similarity exercises are provided to illustrate the practical implementation of the principles discussed.

The first FDA marketing authorizations of next-generation sequencing technology and tests: challenges, solutions and impact for future assays.

PubMed

Bijwaard, Karen; Dickey, Jennifer S; Kelm, Kellie; Težak, Živana

2015-01-01

The rapid emergence and clinical translation of novel high-throughput sequencing technologies created a need to clarify the regulatory pathway for the evaluation and authorization of these unique technologies. Recently, the US FDA authorized for marketing four next generation sequencing (NGS)-based diagnostic devices which consisted of two heritable disease-specific assays, library preparation reagents and a NGS platform that are intended for human germline targeted sequencing from whole blood. These first authorizations can serve as a case study in how different types of NGS-based technology are reviewed by the FDA. In this manuscript we describe challenges associated with the evaluation of these novel technologies and provide an overview of what was reviewed. Besides making validated NGS-based devices available for in vitro diagnostic use, these first authorizations create a regulatory path for similar future instruments and assays.

Industry Perspective on Alopecia Areata.

PubMed

Wagner, Amanda T

2015-11-01

Recent advances in our understanding of the autoimmune basis of alopecia areata provide an opportunity to create novel effective pharmaceutical interventions. The current lack of approved therapies for alopecia areata presents a high unmet medical need, as well as a potentially attractive market opportunity. From an industry perspective, achieving clinical proof of concept (PoC) gates investments into larger approval studies. Recent investigator-initiated experience suggests that it may be possible to demonstrate rigorous PoC for new therapies in an attractive time frame with relatively fewer patients than were believed necessary in the past. However, the lack of prior regulatory approval precedent for pharmaceuticals to treat alopecia areata poses significant development challenges, and early interaction with the FDA and other stakeholders will be critically important in evaluating the path to approval and reimbursement for new treatments for this indication. This paper presents a brief industry perspective on the potential development of new alopecia areata therapeutics.

Innovative strategies for early clinical R&D.

PubMed

Butz, Robert F; Morelli, Gaetano

2008-01-01

Developments in translational medicine and regulatory initiatives associated with the FDA's Critical Path Initiative are creating new opportunities for innovation in early clinical R&D. The introduction of the exploratory IND process allows small, 'phase 0' clinical trials to be conducted prior to traditional phase I trials - sometimes requiring considerably less chemistry, manufacturing and controls, or preclinical support. Phase 0 clinical trials involving subtherapeutic, yet pharmacologically active, dose levels can provide an early demonstration of clinical proof of concept; such demonstration is of particular importance to small pharmaceutical and early-stage biotechnology companies. However, these opportunities for rapid entry into the clinic must be balanced by a consideration of the unique risks associated with first-in-human clinical trials, and by accounting for public concerns regarding drug safety in general. This feature review discusses how innovative clinical strategies can be used effectively in early drug development.

77 FR 55217 - Submission for OMB Review; Comment Request: Cognitive Testing of Instrumentation and Materials...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-07

...; Comment Request: Cognitive Testing of Instrumentation and Materials for the Population Assessment of..., unless it displays a currently valid OMB control number. Proposed Collection: Title: Cognitive Testing of... Administration (FDA). NIDA is requesting generic approval from OMB for cognitive testing of the PATH study's...

Food and Drug Administration: Helping pharmacists ensure that patients receive high-quality medicines.

PubMed

Kremzner, Mary

2016-01-01

Ensuring that the drugs patients take are safe and effective is critical to the Food and Drug Administration (FDA) mission and a major reason for testing an active pharmaceutical ingredient or currently marketed drug product. To address gaps in the assessment of drug quality, FDA's Center for Drug Evaluation and Research (CDER) has created the Office of Pharmaceutical Quality (OPQ). This newly formed "super-office" within CDER launched a concerted new strategy that enhances the surveillance of drug manufacturing and will bring a comprehensive approach to quality oversight. With OPQ and these new performance measures in place, FDA can sharpen its focus on issues critical to quality and can identify and respond to manufacturing issues before they become major systemic problems. Published by Elsevier Inc.

75 FR 47600 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

... (Tobacco Control Act), FDA must conduct research and studies relating to the control and prevention of... such research, FDA will employ formative pretests to assess the likely effectiveness of tobacco..., formative research will provide critical knowledge about target audiences such as adolescents, adults...

78 FR 69689 - Agency Information Collection Activities; Proposed Collection; Comment Request; Hazard Analysis...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-1427... Critical Control Point Procedures for the Safe and Sanitary Processing and Importing of Juice AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

Gaps, tensions, and conflicts in the FDA approval process: implications for clinical practice.

PubMed

Deyo, Richard A

2004-01-01

Despite many successes, drug approval at the Food and Drug Administration (FDA) is subject to gaps, internal tensions, and conflicts of interest. Recalls of drugs and devices and studies demonstrating advantages of older drugs over newer ones highlight the importance of these limitations. The FDA does not compare competing drugs and rarely requires tests of clinical efficacy for new devices. It does not review advertisements before use, assess cost-effectiveness, or regulate surgery (except for devices). Many believe postmarketing surveillance of drugs and devices is inadequate. A source of tension within the agency is pressure for speedy approvals. This may have resulted in "burn-out" among medical officers and has prompted criticism that safety is ignored. Others argue, however, that the agency is unnecessarily slow and bureaucratic. Recent reports identify conflicts of interest (stock ownership, consulting fees, research grants) among some members of the FDA's advisory committees. FDA review serves a critical function, but physicians should be aware that new drugs may not be as effective as old ones; that new drugs are likely to have undiscovered side effects at the time of marketing; that direct-to-consumer ads are sometimes misleading; that new devices generally have less rigorous evidence of efficacy than new drugs; and that value for money is not considered in approval.

Zero-Slack, Noncritical Paths

ERIC Educational Resources Information Center

Simons, Jacob V., Jr.

2017-01-01

The critical path method/program evaluation and review technique method of project scheduling is based on the importance of managing a project's critical path(s). Although a critical path is the longest path through a network, its location in large projects is facilitated by the computation of activity slack. However, logical fallacies in…

76 FR 23823 - Guidance for Industry on Fish and Fishery Products Hazards and Controls, Fourth Edition...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0287... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA... analysis and critical control point (HACCP) methods. DATES: Submit either electronic or written comments on...

Language and Nutrition (Mis)Information: Food Labels, FDA Policies and Meaning

ERIC Educational Resources Information Center

Taylor, Christy Marie

2013-01-01

In this dissertation, I address the ways in which food manufacturers can exploit the often vague and ambiguous nature of FDA policies concerning language and images used on food labels. Employing qualitative analysis methods (Strauss, 1987; Denzin and Lincoln, 2003; Mackey and Gass, 2005) that drew upon critical discourse analysis (Fairclough,…

Blood donation, deferral, and discrimination: FDA donor deferral policy for men who have sex with men.

PubMed

Galarneau, Charlene

2010-02-01

U.S. Food and Drug Administration (FDA) policy prohibits blood donation from men who have had sex with men (MSM) even one time since 1977. Growing moral criticism claims that this policy is discriminatory, a claim rejected by the FDA. An overview of U.S. blood donation, recent donor deferral policy, and the conventional ethical debate introduce the need for a different approach to analyzing discrimination claims. I draw on an institutional understanding of injustice to discern and describe five features of the MSM policy and its FDA context that contribute to its discriminatory effect. I note significant similarities in the 1980s policy of deferring Haitians, suggesting an historical pattern of discrimination in FDA deferral policy. Finally, I point to changes needed to move toward a nondiscriminatory deferral policy.

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status.

PubMed

Singh, Vijay K; Garcia, Melissa; Seed, Thomas M

2017-09-01

The threat of a radiological/nuclear event is a critical concern for all government agencies involved in national security and public health preparedness. Countermeasures that are safe, easily administered, and effective at diminishing or eliminating adverse health effects to individuals and the overall public health impact of radiation exposure are urgently needed. Radiation countermeasures included in this three-part series have been classified under various subheadings based specifically on their developmental stages for United States Food and Drug Administration (FDA) approval. We have included FDA-approved agents for acute radiation syndrome (ARS) in part I. This is part II in which we have reviewed FDA-approved agents for limited indications, internalized radionuclides, emesis, late effects, radiomitigators available in the strategic national stockpile (SNS), agents with FDA investigational new drug (IND) status, and those with NHP efficacy data without FDA IND. Agents discussed in part III are those agents that have been peer reviewed, published, and have demonstrated significant survival benefits in animal models of ARS. Agents investigated in in vitro models only or studied in animal models without peer-reviewed publications have not been included. The dearth of FDA-approved radiation countermeasures has prompted intensified research for a new generation of radiation countermeasures. A number of promising radiation countermeasures are currently moving forward with continued support and effort by both governmental agencies and by publicly and privately held pharmaceutical companies. There is a limited number of countermeasures which are progressing well following the Animal Rule and may get approved in the near future, thus serving to close the gap of this critically important, unmet radiobiomedical need.

Implementing the Biopharmaceutics Classification System in Drug Development: Reconciling Similarities, Differences, and Shared Challenges in the EMA and US-FDA-Recommended Approaches.

PubMed

Cardot, J-M; Garcia Arieta, A; Paixao, P; Tasevska, I; Davit, B

2016-07-01

The US-FDA recently posted a draft guideline for industry recommending procedures necessary to obtain a biowaiver for immediate-release oral dosage forms based on the Biopharmaceutics Classification System (BCS). This review compares the present FDA BCS biowaiver approach, with the existing European Medicines Agency (EMA) approach, with an emphasis on similarities, difficulties, and shared challenges. Some specifics of the current EMA BCS guideline are compared with those in the recently published draft US-FDA BCS guideline. In particular, similarities and differences in the EMA versus US-FDA approaches to establishing drug solubility, permeability, dissolution, and formulation suitability for BCS biowaiver are critically reviewed. Several case studies are presented to illustrate the (i) challenges of applying for BCS biowaivers for global registration in the face of differences in the EMA and US-FDA BCS biowaiver criteria, as well as (ii) challenges inherent in applying for BCS class I or III designation and common to both jurisdictions.

Surgeon Training in Telerobotic Surgery via a Hardware-in-the-Loop Simulator

PubMed Central

Alemzadeh, Homa; Chen, Daniel; Kalbarczyk, Zbigniew; Iyer, Ravishankar K.; Kesavadas, Thenkurussi

2017-01-01

This work presents a software and hardware framework for a telerobotic surgery safety and motor skill training simulator. The aims are at providing trainees a comprehensive simulator for acquiring essential skills to perform telerobotic surgery. Existing commercial robotic surgery simulators lack features for safety training and optimal motion planning, which are critical factors in ensuring patient safety and efficiency in operation. In this work, we propose a hardware-in-the-loop simulator directly introducing these two features. The proposed simulator is built upon the Raven-II™ open source surgical robot, integrated with a physics engine and a safety hazard injection engine. Also, a Fast Marching Tree-based motion planning algorithm is used to help trainee learn the optimal instrument motion patterns. The main contributions of this work are (1) reproducing safety hazards events, related to da Vinci™ system, reported to the FDA MAUDE database, with a novel haptic feedback strategy to provide feedback to the operator when the underlying dynamics differ from the real robot's states so that the operator will be aware and can mitigate the negative impact of the safety-critical events, and (2) using motion planner to generate semioptimal path in an interactive robotic surgery training environment. PMID:29065635

The Food and Drug Administration advisory committees and panels: how they are applied to the drug regulatory process.

PubMed

Ciociola, Arthur A; Karlstadt, Robyn G; Pambianco, Daniel J; Woods, Karen L; Ehrenpreis, Eli D

2014-10-01

Food and Drug Administration (FDA) advisory panels and committees play a critical role in advising the FDA on the safety and efficacy of medical devices and drugs marketed in the US. Advisory panel recommendations are used by the FDA to make decisions regarding medical products. Currently, the FDA utilizes over 50 advisory panels that serve the three major FDA centers, including the Centers for Biologics, Drugs and Device Products. Members of an advisory panel typically include academicians, clinicians, consumers, patients, and industry representatives. The FDA establishes the schedules for advisory panel meetings on an annual basis and a panel usually meets several times a year for two consecutive days in Washington, DC. Typically, the advisory panel discusses issues highlighted by the FDA and is then asked to vote a response to the questions posed in advance by the FDA. Advisory panel recommendations have a strong influence on FDA's decision to approve a product, as evidenced by the 214 Advisory Panels FDA convened between January 2008 to November 2012, during which advisory panel members voted to approve the product (or use of the product) ∼74% of the time, with FDA ultimately approving the medical product (or use of the product) ∼79% of the time. The ACG membership are encouraged to consider serving the public's interest by participating in an FDA advisory panel utilizing their expertise for the evaluation of a new drug or medical device, and providing advice about whether the product should be sold in the US.

Can Congress Get 'Right to Try' Right?

PubMed

Kirkner, Richard Mark

2018-05-01

A federal bill would expand access to experimental treatments to seriously ill patients, but critics say the right to try would take away FDA oversight and create a "Wild West." Proponents counter that the FDA's current process can be onerous for people with just a few months to live. Meanwhile, most states' right-to-try laws have gone unused.

In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products: Workshop Proceedings, Conclusions, and Paths Forward for In Vitro Model Use

EPA Science Inventory

In 2009, the passing of The Family Smoking Prevention and Tobacco Control Act facilitated the establishment of the FDA Center for Tobacco Products (CTP) and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed “...

Science, law, and politics in the Food and Drug Administration's genetically engineered foods policy: FDA's 1992 policy statement.

PubMed

Pelletier, David L

2005-05-01

The US Food and Drug Administration's (FDA's) 1992 policy statement was developed in the context of critical gaps in scientific knowledge concerning the compositional effects of genetic transformation and severe limitations in methods for safety testing. FDA acknowledged that pleiotropy and insertional mutagenesis may cause unintended changes, but it was unknown whether this happens to a greater extent in genetic engineering compared with traditional breeding. Moreover, the agency was not able to identify methods by which producers could screen for unintended allergens and toxicants. Despite these uncertainties, FDA granted genetically engineered foods the presumption of GRAS (Generally Recognized As Safe) and recommended that producers use voluntary consultations before marketing them.

A Critical Review of Methods to Evaluate the Impact of FDA Regulatory Actions

PubMed Central

Briesacher, Becky A.; Soumerai, Stephen B.; Zhang, Fang; Toh, Sengwee; Andrade, Susan E.; Wagner, Joann L.; Shoaibi, Azadeh; Gurwitz, Jerry H.

2013-01-01

Purpose To conduct a synthesis of the literature on methods to evaluate the impacts of FDA regulatory actions, and identify best practices for future evaluations. Methods We searched MEDLINE for manuscripts published between January 1948 and August 2011 that included terms related to FDA, regulatory actions, and empirical evaluation; the review additionally included FDA-identified literature. We used a modified Delphi method to identify preferred methodologies. We included studies with explicit methods to address threats to validity, and identified designs and analytic methods with strong internal validity that have been applied to other policy evaluations. Results We included 18 studies out of 243 abstracts and papers screened. Overall, analytic rigor in prior evaluations of FDA regulatory actions varied considerably; less than a quarter of studies (22%) included control groups. Only 56% assessed changes in the use of substitute products/services, and 11% examined patient health outcomes. Among studies meeting minimal criteria of rigor, 50% found no impact or weak/modest impacts of FDA actions and 33% detected unintended consequences. Among those studies finding significant intended effects of FDA actions, all cited the importance of intensive communication efforts. There are preferred methods with strong internal validity that have yet to be applied to evaluations of FDA regulatory actions. Conclusions Rigorous evaluations of the impact of FDA regulatory actions have been limited and infrequent. Several methods with strong internal validity are available to improve trustworthiness of future evaluations of FDA policies. PMID:23847020

Evidentiary Support in Public Comments to the FDA's Center for Tobacco Products.

PubMed

Hemmerich, Natalie; Klein, Elizabeth G; Berman, Micah

2017-08-01

Electronic Nicotine Delivery Systems (ENDS) were introduced into the US market in 2007, and until recently these devices were unregulated at the federal level. In 2014, the US Food and Drug Administration (FDA) published a Notice of Proposed Rulemaking asserting its intention to regulate ENDS and requesting public comments on numerous related issues, including potential limits on the sale of flavored ENDS. This article analyzes key comments submitted to the FDA on the issue of flavor regulation in ENDS and examines the weight and credibility of the evidence presented by both supporters and opponents of regulation. It also describes the final deeming rule, published in May 2016, and the FDA's response to the evidence submitted. This is the first study to examine public comments submitted to the FDA's Center for Tobacco Products, and it concludes that opponents of regulation were more likely to rely on sources that were not peer reviewed and that were affected by conflicts of interest. In light of these findings, the FDA and the research community should develop processes to carefully and critically analyze public comments submitted to the FDA on issues of tobacco regulation. Copyright © 2017 by Duke University Press.

High-risk medical devices, children and the FDA: regulatory challenges facing pediatric mechanical circulatory support devices.

PubMed

Almond, Christopher S D; Chen, Eric A; Berman, Michael R; Less, Joanne R; Baldwin, J Timothy; Linde-Feucht, Sarah R; Hoke, Tracey R; Pearson, Gail D; Jenkins, Kathy; Duncan, Brian W; Zuckerman, Bram D

2007-01-01

Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.

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.

The Prescription Drug User Fee Act: Cause for Concern?

PubMed

Gabay, Michael

2018-04-01

The Prescription Drug User Fee Act (PDUFA) was originally enacted into law in 1992. PDUFA provides the Food and Drug Administration (FDA) with needed revenue in the form of various fees paid by drug and biologic manufacturers. The FDA utilizes this revenue to streamline the review and approval process for medications. Since the enactment of PDUFA, the median approval time for priority new drug applications and biologics license applications has reduced significantly. The FDA views PDUFA as a successful program that provides a consistent revenue stream to the agency, improves access to medications for patients, and allows industry to have a more predictable product review timeline. However, critics of PDUFA cite concerns including the potential for a lack of FDA independence and medication safety issues involving drugs approved after the existence of PDUFA.

Simulating Mission Command for Planning and Analysis

DTIC Science & Technology

2015-06-01

mission plan. 14. SUBJECT TERMS Mission Planning, CPM , PERT, Simulation, DES, Simkit, Triangle Distribution, Critical Path 15. NUMBER OF...Battalion Task Force CO Company CPM Critical Path Method DES Discrete Event Simulation FA BAT Field Artillery Battalion FEL Future Event List FIST...management tools that can be utilized to find the critical path in military projects. These are the Critical Path Method ( CPM ) and the Program Evaluation and

Strategic Regulatory Evaluation and Endorsement of the Hollow Fiber Tuberculosis System as a Novel Drug Development Tool.

PubMed

Romero, Klaus; Clay, Robert; Hanna, Debra

2015-08-15

The first nonclinical drug development tool (DDT) advanced by the Critical Path to TB Drug Regimens (CPTR) Initiative through a regulatory review process has been endorsed by leading global regulatory authorities. DDTs with demonstrated predictive accuracy for clinical and microbiological outcomes are needed to support decision making. Regulatory endorsement of these DDTs is critical for drug developers, as it promotes confidence in their use in Investigational New Drug and New Drug Application filings. The in vitro hollow fiber system model of tuberculosis (HFS-TB) is able to recapitulate concentration-time profiles (exposure) observed in patients for single drugs and combinations, by evaluating exposure measures for the ability to kill tuberculosis in different physiologic conditions. Monte Carlo simulations make this quantitative output useful to inform susceptibility breakpoints, dosage, and optimal combination regimens in patients, and to design nonclinical experiments in animal models. The Pre-Clinical and Clinical Sciences Working Group within CPTR executed an evidence-based evaluation of the HFS-TB for predictive accuracy. This extensive effort was enabled through the collaboration of subject matter experts representing the pharmaceutical industry, academia, product development partnerships, and regulatory authorities including the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). A comprehensive analysis plan following the regulatory guidance documents for DDT qualification was developed, followed by individual discussions with the FDA and the EMA. The results from the quantitative analyses were submitted to both agencies, pursuing regulatory DDT endorsement. The EMA Qualification Opinion for the HFS-TB DDT was published 26 January 2015 (available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000319.jsp). © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Real-World Evidence, Public Participation, and the FDA.

PubMed

Schwartz, Jason L

2017-11-01

For observers of pharmaceutical regulation and the Food and Drug Administration, these are uncertain times. Events in late 2016 raised concerns that the FDA's evidentiary standards were being weakened, compromising the agency's ability to adequately perform its regulatory and public health responsibilities. Two developments most directly contributed to these fears-the approval of eteplirsen, a treatment for Duchenne muscular dystrophy, against the recommendations of both FDA staff and an advisory committee and the December 2016 signing of the 21st Century Cures Act, which encouraged greater use by the FDA of "real-world" evidence not obtained through randomized controlled trials. The arrival of the Trump administration-with its deregulatory, industry-friendly approach-has only amplified concerns over the future of the FDA. It is too early to know whether the recent developments are truly harbingers of an FDA less likely to prevent unsafe or ineffective products from reaching the market. But elements in the two events-the role of patient narratives in deliberations regarding eteplirsen and the enthusiasm for real-world evidence in the 21st Century Cures Act-raise critical issues for the future of evidence in the FDA's work. The rigorous, inclusive approach under way to consider issues related to real-world evidence provides a model for a similarly needed inquiry regarding public participation in FDA decision-making. © 2017 The Hastings Center.

Pharmacogenomics in the assessment of therapeutic risks versus benefits: inside the United States Food and Drug Administration.

PubMed

Zineh, Issam; Pacanowski, Michael A

2011-08-01

Pharmacogenomics is the study of how genetic variations influence responses to drugs, diagnostics, or biologic agents. The field of pharmacogenomics has significant potential to enhance drug development and aid in making regulatory decisions. The United States Food and Drug Administration (FDA) has supported pharmacogenomics for nearly a decade by providing regulatory advice and reviewing applications, with the intent of discovering and applying genetic determinants of treatment effects. The FDA will continue to develop policies and processes centered on genomics and individualized therapeutics to guide rational drug development. It will also continue to inform the public of clinically relevant pharmacogenomic issues through various mechanisms of communication, such as drug labeling. In this review, we provide a perspective on several pharmacogenomic activities at the FDA. In addition, we attempt to clarify what we believe are several misperceptions regarding the FDA's pharmacogenomic initiatives. We hope this perspective provides a window into some ways in which the FDA is enabling individualized therapeutics through its mission-critical activities.

Price, performance, and the FDA approval process: the example of home HIV testing.

PubMed

Paltiel, A David; Pollack, Harold A

2010-01-01

The Food and Drug Administration (FDA) is considering approval of an over-the-counter, rapid HIV test for home use. To support its decision, the FDA seeks evidence of the test's performance. It has asked the manufacturer to conduct field studies of the test's sensitivity and specificity when employed by untrained users. In this article, the authors argue that additional information should be sought to evaluate the prevalence of undetected HIV in the end-user The analytic framework produces the elementary but counterintuitive finding that the performance of the home HIV test- measured in terms of its ability to correctly detect the presence and absence of HIV infection among the people who purchase it-depends critically on the manufacturer's retail price. This finding has profound implications for the FDA's approval process.

Sustainability, Innovation, and the Future of Environmental Protection

DTIC Science & Technology

2010-09-01

Sustainability, & chemical product design Coffee decaffeination using methylene chloride Coffee decaffeination using CO2 (not a “solvent” by FDA) Coffee beans ...contin.) • Materials sustainability – Trace metals • Security of supply chain • Appropriate selection and use • Mass balance on use, reuse, and...Design • Transdisciplinary Collaboration and Integrative Systems • Innovation and Catalysis Scientific Values for the Path Forward 17 Office of

The U.S. Food and Drug Administration's Evaluation of the Safety of Animal Clones: A Failure to Recognize the Normativity of Risk Assessment Projects

ERIC Educational Resources Information Center

Meghani, Zahra; de Melo-Martin, Inmaculada

2009-01-01

The U.S. Food and Drug Administration (FDA) announced recently that food products derived from some animal clones and their offspring are safe for human consumption. In response to criticism that it had failed to engage with ethical, social, and economic concerns raised by livestock cloning, the FDA argued that addressing normative issues prior to…

FDA regulation of tobacco: blessing or curse for FDA professionals?

PubMed

O'Reilly, James T

2009-01-01

Upwards of 400,000 Americans will die that year from the effects of cigarettes, which FDA will now "regulate" very gently, with its hands tied by a slick statutory protection for the largest existing tobacco marketers. Career FDA professionals will be criticized as enablers of mega-marketers' continued sales, working at the margins, arranging the paperwork for protection of megafirms' market share, and sitting by as the deaths and addictive behaviors continue. "Join the Public Health Service, inspired by a public health mission," they were told, and yet they will be unable to do much regulating of the addictive and fatal products for which they now have titular responsibility. This essay observes that these fine FDA professionals are handed the sticky remains of a messy bargain, negotiated in a distracted Congress by expensive lawyers with clients who were potent contributors to political action committees. The only formula that is not secret about the 2009 law is the way in which industry purchased sufficient allegiance to gather the votes for its adoption. The remaining mystery is how FDA could be expected to do these tasks without losing its best and brightest professionals to other fields.

Compounding pharmacy conundrum: "we cannot live without them but we cannot live with them" according to the present paradigm.

PubMed

Guharoy, Roy; Noviasky, John; Haydar, Ziad; Fakih, Mohamad G; Hartman, Christian

2013-04-01

Compounding pharmacies serve a critical role in modern health care to meet special patient care needs. Although the US Food and Drug Administration (FDA) has clearly delineated jurisdiction over drug companies and products manufactured under Good Manufacturing Practice (GMP) regulations to ensure quality, potency, and purity, compounding pharmacies are regulated by the State Boards and are not registered by the FDA. In recent years, some compounding pharmacies acted like a manufacturer, preparing large amounts of injectable drugs with interstate activities. Multiple outbreaks have been linked to compounding pharmacies, including a recent outbreak of fungal meningitis related to contaminated methylprednisolone, exposing > 14,000 patients in multiple states. This tragedy underscores the urgency of addressing safety related to compounding pharmacies. There is a call for action at the federal and state levels to set minimum production standards, impose new labeling conditions on compounded drugs, and require large-scale compounders be regulated by the FDA. "Industrial" compounding must come under FDA oversight, require those pharmacies to meet GMP standards, and ensure quality and safe products for patient use. Moreover, compliance with the Institute for Safe Medication Practices 2011 recommendations that any type of sterile compounding must be in compliance with the United States Pharmacopoeia chapter 797 guidelines will reduce the risk of patient harm from microbial contamination. Finally, other critical factors that require close attention include addressing injectable products compounded in hospitals and other outpatient health-care centers. The FDA and State Boards of Pharmacy must be adequately funded to exercise the oversight effectively.

Use of a High-Flow Oxygen Delivery System in a Critically Ill Patient with Dementia

DTIC Science & Technology

2008-12-01

February 1, 2007. http://www.fda.gov/ cdrh /safety/ 020107_vapotherm.html. Accessed October 7, 2008. HIGH-FLOW OXYGEN IN A CRITICALLY ILL PATIENT WITH DEMENTIA RESPIRATORY CARE • DECEMBER 2008 VOL 53 NO 12 1743

Regulatory perspectives and research activities at the FDA on the use of phantoms with in vivo diagnostic devices

NASA Astrophysics Data System (ADS)

Agrawal, Anant; Gavrielides, Marios A.; Weininger, Sandy; Chakrabarti, Kish; Pfefer, Joshua

2008-02-01

For a number of years, phantoms have been used to optimize device parameters and validate performance in the primary medical imaging modalities (CT, MRI, PET/SPECT, ultrasound). Furthermore, the FDA under the Mammography Quality Standards Act (MQSA) requires image quality evaluation of mammography systems using FDA-approved phantoms. The oldest quantitative optical diagnostic technology, pulse oximetry, also benefits from the use of active phantoms known as patient simulators to validate certain performance characteristics under different clinically-relevant conditions. As such, guidance provided by the FDA to its staff and to industry on the contents of pre-market notification and approval submissions includes suggestions on how to incorporate the appropriate phantoms in establishing device effectiveness. Research at the FDA supports regulatory statements on the use of phantoms by investigating how phantoms can be designed, characterized, and utilized to determine critical device performance characteristics. These examples provide a model for how novel techniques in the rapidly growing field of optical diagnostics can use phantoms during pre- and post-market regulatory testing.

Network-Based Real-time Integrated Fire Detection and Alarm (FDA) System with Building Automation

NASA Astrophysics Data System (ADS)

Anwar, F.; Boby, R. I.; Rashid, M. M.; Alam, M. M.; Shaikh, Z.

2017-11-01

Fire alarm systems have become increasingly an important lifesaving technology in many aspects, such as applications to detect, monitor and control any fire hazard. A large sum of money is being spent annually to install and maintain the fire alarm systems in buildings to protect property and lives from the unexpected spread of fire. Several methods are already developed and it is improving on a daily basis to reduce the cost as well as increase quality. An integrated Fire Detection and Alarm (FDA) systems with building automation was studied, to reduce cost and improve their reliability by preventing false alarm. This work proposes an improved framework for FDA system to ensure a robust intelligent network of FDA control panels in real-time. A shortest path algorithmic was chosen for series of buildings connected by fiber optic network. The framework shares information and communicates with each fire alarm panels connected in peer to peer configuration and declare the network state using network address declaration from any building connected in network. The fiber-optic connection was proposed to reduce signal noises, thus increasing large area coverage, real-time communication and long-term safety. Based on this proposed method an experimental setup was designed and a prototype system was developed to validate the performance in practice. Also, the distributed network system was proposed to connect with an optional remote monitoring terminal panel to validate proposed network performance and ensure fire survivability where the information is sequentially transmitted. The proposed FDA system is different from traditional fire alarm and detection system in terms of topology as it manages group of buildings in an optimal and efficient manner.Introduction

The Human Space Life Sciences Critical Path Roadmap Project: A Strategy for Human Space Flight through Exploration-Class Missions

NASA Technical Reports Server (NTRS)

Sawin, Charles F.

1999-01-01

The product of the critical path roadmap project is an integrated strategy for mitigating the risks associated with human exploration class missions. It is an evolving process that will assure the ability to communicate the integrated critical path roadmap. Unlike previous reports, this one will not sit on a shelf - it has the full support of the JSC Space and Life Sciences Directorate (SA) and is already being used as a decision making tool (e.g., budget and investigation planning for Shuttle and Space Station mission). Utility of this product depends on many efforts, namely: providing the required information (completed risk data sheets, critical question information, technology data). It is essential to communicate the results of the critical path roadmap to the scientific community - this meeting is a good opportunity to do so. The web site envisioned for the critical path roadmap will provide the capability to communicate to a broader community and to track and update the system routinely.

Interpreting labels of abuse-deterrent opioid analgesics.

PubMed

Webster, Lynn R

To provide an overview of available abuse-deterrent opioids (ADOs) and the labeling text that describes abuse-deterrent (AD) properties. A nonsystematic review of ADO literature and regulatory documents guiding their development. A critical assessment and discussion of common routes of opioid abuse, AD methods and properties, US Food and Drug Administration (FDA) study requirements to achieve AD labeling, and brief guide to understanding AD labels. The FDA has issued guidance as incentive and direction to industry to develop ADOs as one component of a multi-pronged public-health strategy to combat opioid abuse and misuse. The guidance describes separate categories of premarket and postmarket studies and makes recommendations for claims that may be made based on study findings. Ten ADOs have FDA-approved labeling attesting to AD properties. Available formulations that fail to conform to FDA guidance in study and labeling recommendations cannot be considered ADO. Formulations with AD properties are expected to reduce risk compared to the same agents without AD properties but cannot prevent all abuse and adverse clinical outcomes.

Regulatory Underpinnings of Global Health Security: FDA's Roles in Preventing, Detecting, and Responding to Global Health Threats

PubMed Central

Bond, Katherine C.; Maher, Carmen

2014-01-01

In February 2014, health officials from around the world announced the Global Health Security Agenda, a critical effort to strengthen national and global systems to prevent, detect, and respond to infectious disease threats and to foster stronger collaboration across borders. With its increasing global roles and broad range of regulatory responsibilities in ensuring the availability, safety, and security of medical and food products, the US Food and Drug Administration (FDA) is engaged in a range of efforts in support of global health security. This article provides an overview of FDA's global health security roles, focusing on its responsibilities related to the development and use of medical countermeasures (MCMs) for preventing, detecting, and responding to global infectious disease and other public health emergency threats. The article also discusses several areas—antimicrobial resistance, food safety, and supply chain integrity—in which FDA's global health security roles continue to evolve and extend beyond MCMs and, in some cases, beyond traditional infectious disease threats. PMID:25254912

Regulatory underpinnings of Global Health security: FDA's roles in preventing, detecting, and responding to global health threats.

PubMed

Courtney, Brooke; Bond, Katherine C; Maher, Carmen

2014-01-01

In February 2014, health officials from around the world announced the Global Health Security Agenda, a critical effort to strengthen national and global systems to prevent, detect, and respond to infectious disease threats and to foster stronger collaboration across borders. With its increasing global roles and broad range of regulatory responsibilities in ensuring the availability, safety, and security of medical and food products, the US Food and Drug Administration (FDA) is engaged in a range of efforts in support of global health security. This article provides an overview of FDA's global health security roles, focusing on its responsibilities related to the development and use of medical countermeasures (MCMs) for preventing, detecting, and responding to global infectious disease and other public health emergency threats. The article also discusses several areas-antimicrobial resistance, food safety, and supply chain integrity-in which FDA's global health security roles continue to evolve and extend beyond MCMs and, in some cases, beyond traditional infectious disease threats.

Preliminary investigation into the analytical potential of a multiwavelength fiber drop analyzer with special reference to applications in medical diagnostics

NASA Astrophysics Data System (ADS)

McMillan, Norman D.; O'Mongain, Eon; Walsh, James E.; Breen, Liam; McMillan, Duncan G.; Power, Michael J.; O'Dea, John P.; Kinsella, Seamus M.; Kelly, Mairead P.; Hammil, Conor; Orr, Dermot

1994-12-01

A preliminary investigation into the use of multiwavelength fiber drop analyzer (FDA) for the measurement of viscosity, spectral absorbance and refractive index is made with a view to obtaining conservative estimates of the instrumental capability of the FDA for these measurands. Some important new insights into drop vibrations are made from studies on the fiber drop traces (FDTs) of mechanically excited damped vibrations in drops with a set volume. A brief description of the feasibility measurements on the first application of the FDA in the diagnosis of disease in synovial fluid is given. Strong experimental evidence is reported for the existence of the surface-guided wave peak of the fiber drop trace and some new insights into the nature of the FDT are suggested based on a comparative study of the FDTs from a multiple-wavelength and a single-wavelength FDA. The earlier reported drop period dependence on applied electric field is critically reexamined, a new interpretation of this effect, is suggested, and an experimental study of clarification is given. Finally, a brief review of the projected capabilities of the FDA based on the work reported here is provided.

The Use of Published Clinical Study Reports to Support U.S. Food and Drug Administration Approval of Imaging Agents.

PubMed

Rieves, Dwaine; Jacobs, Paula

2016-12-01

Pharmaceutical companies typically perform prospective, multicenter phase 3 clinical studies to support approval of a new imaging agent by the U.S. Food and Drug Administration (FDA). In uncommon situations, the FDA has approved imaging agents based solely, or in large part, on the clinical study experience described in published reports, including reports of exploratory (i.e., phase 1 or 2) studies performed at a single clinical site. We performed a survey of published reports to assess the potential of the reported information to support FDA approval of a commonly cited investigational imaging agent. Our survey revealed critical data limitations in most publications, all of which reported exploratory clinical studies. Here we summarize the precedent for FDA approval of imaging agents using effectiveness data from publications, FDA guidance, and our experience in reviewing publications. We also present a key-data checklist for investigators to consider in the design, conduct, and reporting of exploratory clinical studies for publication. We encourage editors and peer reviewers to consider requiring these key data when reviewing these reports for publication. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Think-Aloud Process Superior to Thought-Listing in Increasing Children's Critical Processing of Advertising

ERIC Educational Resources Information Center

Rozendaal, Esther; Buijzen, Moniek; Valkenburg, Patti M.

2012-01-01

This study develops and tests a model of children's critical processing of advertising. Within this model, 2 paths to reduced advertising susceptibility (i.e., attitude toward the advertised brand) were hypothesized: a cognitive path and an affective path. The secondary aim was to compare these paths for different thought verbalization processes:…

Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.

PubMed

Lacy, B E; Lembo, A J; Macdougall, J E; Shiff, S J; Kurtz, C B; Currie, M G; Johnston, J M

2014-03-01

US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies. © 2013 Ironwood Pharmaceuticals. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

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.

Methodological approaches to evaluate the impact of FDA drug safety communications.

PubMed

Kesselheim, Aaron S; Campbell, Eric G; Schneeweiss, Sebastian; Rausch, Paula; Lappin, Brian M; Zhou, Esther H; Seeger, John D; Brownstein, John S; Woloshin, Steven; Schwartz, Lisa M; Toomey, Timothy; Dal Pan, Gerald J; Avorn, Jerry

2015-06-01

When the US FDA approves a new prescription drug there is still a great deal remaining to be learned about the safe and proper use of that product. When new information addressing these topics emerges post-approval, the FDA may issue a Drug Safety Communication (DSC) to alert patients and physicians. The effectiveness of the communication-how drug safety messaging conveyed in FDA DSCs changes patient or prescriber behavior-may depend on multiple factors, including the way physicians and patients learn about the information, their understanding of the issues conveyed, and their perception of the importance of the information. In 2013, the FDA issued two DSCs addressing critical new warnings related to products containing the sedative/hypnotic zolpidem. In this article, we describe a core set of research initiatives that can be used to study how zolpidem-related DSCs affected subsequent physician and patient decision making. These research initiatives include analyzing drug utilization patterns and related health outcomes; comparing zolpidem-containing products against a comparator with similar indications [eszopiclone (Lunesta)] not covered by the 2013 DSCs; and surveying patients and qualitatively evaluating the dissemination of information regarding these drugs in traditional and social-media channels. Using an integrated, multidisciplinary approach, we can obtain information that can be used to optimize regulatory communications by seeking to understand the impact of the information contained in FDA risk communications.

Regulating nanomedicine - can the FDA handle it?

PubMed

Bawa, Raj

2011-05-01

There is enormous excitement and expectation surrounding the multidisciplinary field of nanomedicine - the application of nanotechnology to healthcare - which is already influencing the pharmaceutical industry. This is especially true in the design, formulation and delivery of therapeutics. Currently, nanomedicine is poised at a critical stage. However, regulatory guidance in this area is generally lacking and critically needed to provide clarity and legal certainty to manufacturers, policymakers, healthcare providers as well as public. There are hundreds, if not thousands, of nanoproducts on the market for human use but little is known of their health risks, safety data and toxicity profiles. Less is known of nanoproducts that are released into the environment and that come in contact with humans. These nanoproducts, whether they are a drug, device, biologic or combination of any of these, are creating challenges for the Food and Drug Administration (FDA), as regulators struggle to accumulate data and formulate testing criteria to ensure development of safe and efficacious nanoproducts (products incorporating nanoscale technologies). Evidence continues to mount that many nanoproducts inherently posses novel size-based properties and toxicity profiles. Yet, this scientific fact has been generally ignored by the FDA and the agency continues to adopt a precautionary approach to the issue in hopes of countering future potential negative public opinion. As a result, the FDA has simply maintained the status quo with regard to its regulatory policies pertaining to nanomedicine. Therefore, there are no specific laws or mechanisms in place for oversight of nanomedicine and the FDA continues to treat nanoproducts as substantially equivalent ("bioequivalent") to their bulk counterparts. So, for now nanoproducts submitted for FDA review will continue to be subjected to an uncertain regulatory pathway. Such regulatory uncertainty could negatively impact venture funding, stifle nanomedicine research and development (R&D) and erode public acceptance of nanoproducts. The end-result of this could be a delay or loss of commercialized nanoproducts. Whether the FDA eventually creates new regulations, tweaks existing ones or establishes a new regulatory center to handle nanoproducts, for the time being it should at least look at nanoproducts on a case-by-case basis. The FDA should not attempt regulation of nanomedicine by applying existing statutes alone, especially where scientific evidence suggests otherwise. Incorporating nanomedicine regulation into the current regulatory scheme is a poor idea. Regulation of nanomedicine must balance innovation and R&D with the principle of ensuring maximum public health protection and safety.

Synthetic risks, risk potency, and carcinogen regulation.

PubMed

Viscusi, W K; Hakes, J K

1998-01-01

This article analyzes a comprehensive sample of over 350 chemicals tested for carcinogenicity to assess the determinants of the probability of regulation. Controlling for differences in the risk potency and noncancer risks, synthetic chemicals have a significantly higher probability of regulation overall: this is due to the greater likelihood of U.S. Food and Drug Administration (FDA) regulation. Measures of risk potency increase the probability of regulation by the U.S. Environmental Protection Agency (EPA), have a somewhat weaker positive effect on regulation by the U.S. Occupational Safety and Health Administration (OSHA), and decrease the likelihood of regulation by the FDA. The overall regulatory pattern is one in which the FDA targets synthetic chemicals and chemicals that pose relatively minor cancer risk. The EPA particularly performed more sensibly than many critics have suggested.

Meeting the challenges of medical countermeasure development

PubMed Central

Maher, Carmen; Hu‐Primmer, Jean; MacGill, Tracy; Courtney, Brooke; Borio, Luciana

2012-01-01

Summary Despite substantial investments since the events of 2001, much work remains to prepare the nation for a chemical, biological, radiological or nuclear (CBRN) attack or to respond to an emerging infectious disease threat. Following a 2010 review of the US Public Health Emergency Medical Countermeasures Enterprise, FDA launched its Medical Countermeasures initiative (MCMi) to facilitate the development and availability of medical products to counter CBRN and emerging disease threats. As a regulatory agency, FDA has a unique and critical part to play in this national undertaking. Using a three‐pillar approach, FDA is addressing key challenges associated with the regulatory review process for medical countermeasures; gaps in regulatory science for MCM development and evaluation; and issues related to the legal, regulatory and policy framework for an effective public health response. Filling the gaps in the MCM Enterprise is a huge national undertaking, requiring the collaboration of all stakeholders, including federal partners, current and prospective developers of medical countermeasures, relevant research organizations, and state and local responders. Especially critical to success are an appreciation of the long timelines, risks and high costs associated with developing medical countermeasures – and the systems to deliver them – and the requisite support of all stakeholders, including national leadership. PMID:22925432

Regulatory administrative databases in FDA's Center for Biologics Evaluation and Research: convergence toward a unified database.

PubMed

Smith, Jeffrey K

2013-04-01

Regulatory administrative database systems within the Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) are essential to supporting its core mission, as a regulatory agency. Such systems are used within FDA to manage information and processes surrounding the processing, review, and tracking of investigational and marketed product submissions. This is an area of increasing interest in the pharmaceutical industry and has been a topic at trade association conferences (Buckley 2012). Such databases in CBER are complex, not for the type or relevance of the data to any particular scientific discipline but because of the variety of regulatory submission types and processes the systems support using the data. Commonalities among different data domains of CBER's regulatory administrative databases are discussed. These commonalities have evolved enough to constitute real database convergence and provide a valuable asset for business process intelligence. Balancing review workload across staff, exploring areas of risk in review capacity, process improvement, and presenting a clear and comprehensive landscape of review obligations are just some of the opportunities of such intelligence. This convergence has been occurring in the presence of usual forces that tend to drive information technology (IT) systems development toward separate stovepipes and data silos. CBER has achieved a significant level of convergence through a gradual process, using a clear goal, agreed upon development practices, and transparency of database objects, rather than through a single, discrete project or IT vendor solution. This approach offers a path forward for FDA systems toward a unified database.

Laboratory-based testing to evaluate abuse-deterrent formulations and satisfy the Food and Drug Administration's recommendation for Category 1 Testing.

PubMed

Altomare, Christopher; Kinzler, Eric R; Buchhalter, August R; Cone, Edward J; Costantino, Anthony

The US Food and Drug Administration (FDA) considers the development of abuse-deterrent formulations of solid oral dosage forms a public health priority and has outlined a series of premarket studies that should be performed prior to submitting an application to the Agency. Category 1 studies are performed to characterize whether the abuse-deterrent properties of a new formulation can be easily defeated. Study protocols are designed to evaluate common abuse patterns of prescription medications as well as more advanced methods that have been reported on drug abuse websites and forums. Because FDA believes Category 1 testing should fully characterize the abuse-deterrent characteristics of an investigational formulation, Category 1 testing is time consuming and requires specialized laboratory resources as well as advanced knowledge of prescription medication abuse. Recent Advisory Committee meetings at FDA have shown that Category 1 tests play a critical role in FDA's evaluation of an investigational formulation. In this article, we will provide a general overview of the methods of manipulation and routes of administration commonly utilized by prescription drug abusers, how those methods and routes are evaluated in a laboratory setting, and discuss data intake, analysis, and reporting to satisfy FDA's Category 1 testing requirements.

Meeting the challenges of medical countermeasure development.

PubMed

Maher, Carmen; Hu-Primmer, Jean; MacGill, Tracy; Courtney, Brooke; Borio, Luciana

2012-09-01

Despite substantial investments since the events of 2001, much work remains to prepare the nation for a chemical, biological, radiological or nuclear (CBRN) attack or to respond to an emerging infectious disease threat. Following a 2010 review of the US Public Health Emergency Medical Countermeasures Enterprise, FDA launched its Medical Countermeasures initiative (MCMi) to facilitate the development and availability of medical products to counter CBRN and emerging disease threats. As a regulatory agency, FDA has a unique and critical part to play in this national undertaking. Using a three-pillar approach, FDA is addressing key challenges associated with the regulatory review process for medical countermeasures; gaps in regulatory science for MCM development and evaluation; and issues related to the legal, regulatory and policy framework for an effective public health response. Filling the gaps in the MCM Enterprise is a huge national undertaking, requiring the collaboration of all stakeholders, including federal partners, current and prospective developers of medical countermeasures, relevant research organizations, and state and local responders. Especially critical to success are an appreciation of the long timelines, risks and high costs associated with developing medical countermeasures - and the systems to deliver them - and the requisite support of all stakeholders, including national leadership. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

An Interactive User Interface for Drug Labeling to Improve Readability and Decision-Making

PubMed Central

Abedtash, Hamed; Duke, Jon D.

2015-01-01

FDA-approved prescribing information (also known as product labeling or labels) contain critical safety information for health care professionals. Drug labels have often been criticized, however, for being overly complex, difficult to read, and rife with overwarning, leading to high cognitive load. In this project, we aimed to improve the usability of drug labels by increasing the ‘signal-to-noise ratio’ and providing meaningful information to care providers based on patient-specific comorbidities and concomitant medications. In the current paper, we describe the design process and resulting web application, known as myDrugLabel. Using the Structured Product Label documents as a base, we describe the process of label personalization, readability improvements, and integration of diverse evidence sources, including the medical literature from PubMed, pharmacovigilance reports from FDA adverse event reporting system (FAERS), and social media signals directly into the label. PMID:26958158

An Interactive User Interface for Drug Labeling to Improve Readability and Decision-Making.

PubMed

Abedtash, Hamed; Duke, Jon D

FDA-approved prescribing information (also known as product labeling or labels) contain critical safety information for health care professionals. Drug labels have often been criticized, however, for being overly complex, difficult to read, and rife with overwarning, leading to high cognitive load. In this project, we aimed to improve the usability of drug labels by increasing the 'signal-to-noise ratio' and providing meaningful information to care providers based on patient-specific comorbidities and concomitant medications. In the current paper, we describe the design process and resulting web application, known as myDrugLabel. Using the Structured Product Label documents as a base, we describe the process of label personalization, readability improvements, and integration of diverse evidence sources, including the medical literature from PubMed, pharmacovigilance reports from FDA adverse event reporting system (FAERS), and social media signals directly into the label.

Advancing the science for active surveillance: rationale and design for the Observational Medical Outcomes Partnership.

PubMed

Stang, Paul E; Ryan, Patrick B; Racoosin, Judith A; Overhage, J Marc; Hartzema, Abraham G; Reich, Christian; Welebob, Emily; Scarnecchia, Thomas; Woodcock, Janet

2010-11-02

The U.S. Food and Drug Administration (FDA) Amendments Act of 2007 mandated that the FDA develop a system for using automated health care data to identify risks of marketed drugs and other medical products. The Observational Medical Outcomes Partnership is a public-private partnership among the FDA, academia, data owners, and the pharmaceutical industry that is responding to the need to advance the science of active medical product safety surveillance by using existing observational databases. The Observational Medical Outcomes Partnership's transparent, open innovation approach is designed to systematically and empirically study critical governance, data resource, and methodological issues and their interrelationships in establishing a viable national program of active drug safety surveillance by using observational data. This article describes the governance structure, data-access model, methods-testing approach, and technology development of this effort, as well as the work that has been initiated.

Alarm guided critical function and success path monitoring

DOEpatents

Scarola, Kenneth; Jamison, David S.; Manazir, Richard M.; Rescorl, Robert L.; Harmon, Daryl L.

1994-01-01

The use of alarm indication on the overview (IPSO) display to initiate diagnosis of challenges to critical functions or unavailability of success paths, and further alarm-based guidance toward ultimate diagnosis.

Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

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

Valerio, Luis G.; Arvidson, Kirk B.; Chanderbhan, Ronald F.

2007-07-01

Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest ismore » MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals, comprised primarily of pharmaceutical, industrial and some natural products developed under an FDA-MDL cooperative research and development agreement (CRADA). The predictive performance for this group of dietary natural products and the control group was 97% sensitivity and 80% concordance. Specificity was marginal at 53%. This study finds that the in silico QSAR analysis employing this software's rodent carcinogenicity database is capable of identifying the rodent carcinogenic potential of naturally occurring organic molecules found in the human diet with a high degree of sensitivity. It is the first study to demonstrate successful QSAR predictive modeling of naturally occurring carcinogens found in the human diet using an external validation test. Further test validation of this software and expansion of the training data set for dietary chemicals will help to support the future use of such QSAR methods for screening and prioritizing the risk of dietary chemicals when actual animal data are inadequate, equivocal, or absent.« less

A decade of direct-to-consumer advertising of prescription drugs.

PubMed

Donohue, Julie M; Cevasco, Marisa; Rosenthal, Meredith B

2007-08-16

Evidence suggests that direct-to-consumer advertising of prescription drugs increases pharmaceutical sales and both helps to avert underuse of medicines and leads to potential overuse. Concern about such advertising has increased recently owing to the withdrawal from the market of heavily advertised drugs found to carry serious risks. Moreover, the Food and Drug Administration (FDA) has been criticized for its weak enforcement of laws regulating such advertising. We examined industry-wide trends in spending by pharmaceutical companies on direct-to-consumer advertising and promotion to physicians during the past decade. We characterized the drugs for which such advertising is used and assessed the timing of advertising after a drug is introduced. Finally, we examined trends in the FDA's regulation of drug advertising. Total spending on pharmaceutical promotion grew from $11.4 billion in 1996 to $29.9 billion in 2005. Although during that time spending on direct-to-consumer advertising increased by 330%, it made up only 14% of total promotional expenditures in 2005. Direct-to-consumer campaigns generally begin within a year after the approval of a product by the FDA. In the context of regulatory changes requiring legal review before issuing letters, the number of letters sent by the FDA to pharmaceutical manufacturers regarding violations of drug-advertising regulations fell from 142 in 1997 to only 21 in 2006. Spending on direct-to-consumer advertising has continued to increase in recent years in spite of the criticisms leveled against it. Our findings suggest that calls for a moratorium on such advertising for new drugs would represent a dramatic departure from current practices. Copyright 2007 Massachusetts Medical Society.

Maintaining Life-saving Testing for Patients With Infectious Diseases: Infectious Diseases Society of America, American Society for Microbiology, and Pan American Society for Clinical Virology Recommendations on the Regulation of Laboratory-developed Tests.

PubMed

Caliendo, Angela M; Couturier, Marc R; Ginocchio, Christine C; Hanson, Kimberly E; Miller, Melissa B; Walker, Kimberly E; Frank, Gregory M

2016-07-15

In 2014, the US Food and Drug Administration (FDA) proposed to regulate laboratory-developed tests (LDTs)-diagnostics designed, manufactured, and used within a single laboratory. The Infectious Diseases Society of America, the American Society for Microbiology, and the Pan American Society for Clinical Virology recognize that the FDA is committed to protecting patients. However, our societies are concerned that the proposed regulations will limit access to testing and negatively impact infectious diseases (ID) LDTs. In this joint commentary, our societies discuss why LDTs are critical for ID patient care, hospital infection control, and public health responses. We also highlight how the FDA's proposed regulation of LDTs could impair patient access to life-saving tests and stifle innovation in ID diagnostics. Finally, our societies make specific recommendations for the FDA's consideration to reduce the burden of the proposed new rules on clinical laboratories and protect patients' access to state-of-the art, quality LDTs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

77 FR 13513 - Modernizing the Regulation of Clinical Trials and Approaches to Good Clinical Practice; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-07

...The Food and Drug Administration (FDA) is announcing a 2-day public hearing to obtain input from interested persons on FDA's scope and direction in modernizing the regulations, policies, and practices that apply to the conduct of clinical trials of FDA-regulated products. Clinical trials are a critical source of evidence to inform medical policy and practice, and effective regulatory oversight is needed to ensure that human subjects are protected and resulting clinical trial data are credible and accurate. FDA is aware of concerns within the clinical trial community that certain regulations and policies applicable to the conduct of clinical trials may result in inefficiencies or increased cost and may not facilitate the use of innovative methods and technological advances to improve clinical trial quality. The Agency is involved in an effort to modernize the regulatory framework that governs clinical trials and approaches to good clinical practice (GCP). The purpose of this hearing is to solicit public input from a broad group of stakeholders on the scope and direction of this effort, including encouraging the use of innovative models that may enhance the effectiveness and efficiency of the clinical trial enterprise.

Project Scheduling Based on Risk of Gas Transmission Pipe

NASA Astrophysics Data System (ADS)

Silvianita; Nurbaity, A.; Mulyadi, Y.; Suntoyo; Chamelia, D. M.

2018-03-01

The planning of a project has a time limit on which must be completed before or right at a predetermined time. Thus, in a project planning, it is necessary to have scheduling management that is useful for completing a project to achieve maximum results by considering the constraints that will exists. Scheduling management is undertaken to deal with uncertainties and negative impacts of time and cost in project completion. This paper explains about scheduling management in gas transmission pipeline project Gresik-Semarang to find out which scheduling plan is most effectively used in accordance with its risk value. Scheduling management in this paper is assissted by Microsoft Project software to find the critical path of existing project scheduling planning data. Critical path is the longest scheduling path with the fastest completion time. The result is found a critical path on project scheduling with completion time is 152 days. Furthermore, the calculation of risk is done by using House of Risk (HOR) method and it is found that the critical path has a share of 40.98 percent of all causes of the occurence of risk events that will be experienced.

In vitro exposure systems and dosimetry assessment tools for inhaled tobacco products: Workshop proceedings, conclusions and paths forward for in vitro model use.

PubMed

Behrsing, Holger; Hill, Erin; Raabe, Hans; Tice, Raymond; Fitzpatrick, Suzanne; Devlin, Robert; Pinkerton, Kent; Oberdörster, Günter; Wright, Chris; Wieczorek, Roman; Aufderheide, Michaela; Steiner, Sandro; Krebs, Tobias; Asgharian, Bahman; Corley, Richard; Oldham, Michael; Adamson, Jason; Li, Xiang; Rahman, Irfan; Grego, Sonia; Chu, Pei-Hsuan; McCullough, Shaun; Curren, Rodger

2017-07-01

In 2009, the passing of the Family Smoking Prevention and Tobacco Control Act facilitated the establishment of the FDA Center for Tobacco Products (CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed 'modified risk'. On 4-6 April 2016, the Institute for In Vitro Sciences, Inc. (IIVS) convened a workshop conference entitled, In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products, to bring together stakeholders representing regulatory agencies, academia and industry to address the research priorities articulated by the FDA CTP. Specific topics were covered to assess the status of current in vitro smoke and aerosol/vapour exposure systems, as well as the various approaches and challenges to quantifying the complex exposures in in vitro pulmonary models developed for evaluating adverse pulmonary events resulting from tobacco product exposures. The four core topics covered were: a) Tobacco Smoke and E-Cigarette Aerosols; b) Air-Liquid Interface-In Vitro Exposure Systems; c) Dosimetry Approaches for Particles and Vapours/In Vitro Dosimetry Determinations; and d) Exposure Microenvironment/Physiology of Cells. The 2.5-day workshop included presentations from 20 expert speakers, poster sessions, networking discussions, and breakout sessions which identified key findings and provided recommendations to advance these technologies. Here, we will report on the proceedings, recommendations, and outcome of the April 2016 technical workshop, including paths forward for developing and validating non-animal test methods for tobacco product smoke and next generation tobacco product aerosol/vapour exposures. With the recent FDA publication of the final deeming rule for the governance of tobacco products, there is an unprecedented necessity to evaluate a very large number of tobacco-based products and ingredients. The questionable relevance, high cost, and ethical considerations for the use of in vivo testing methods highlight the necessity of robust in vitro approaches to elucidate tobacco-based exposures and how they may lead to pulmonary diseases that contribute to lung exposure-induced mortality worldwide. 2017 FRAME.

Critical path method applied to research project planning: Fire Economics Evaluation System (FEES)

Treesearch

Earl B. Anderson; R. Stanton Hales

1986-01-01

The critical path method (CPM) of network analysis (a) depicts precedence among the many activities in a project by a network diagram; (b) identifies critical activities by calculating their starting, finishing, and float times; and (c) displays possible schedules by constructing time charts. CPM was applied to the development of the Forest Service's Fire...

Technology assessment and the Food and Drug Administration

NASA Technical Reports Server (NTRS)

Kaplan, A. H.; Becker, R. H.

1972-01-01

The statutory standards underlying the activities of the FDA, and the problems the Agency faces in decision making are discussed from a legal point of view. The premarketing clearance of new drugs and of food additives, the two most publicized and criticized areas of FDA activity, are used as illustrations. The importance of statutory standards in technology assessment in a regulatory setting is developed. The difficulties inherent in the formulation of meaningful standards are recognized. For foods, the words of the statute are inadequate, and for drugs, a statutory recognition of the various other objectives would be useful to the regulator and the regulated.

Primaquine in vivax malaria: an update and review on management issues

PubMed Central

2011-01-01

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs. PMID:22152065

Primaquine in vivax malaria: an update and review on management issues.

PubMed

Fernando, Deepika; Rodrigo, Chaturaka; Rajapakse, Senaka

2011-12-12

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs.

Re-evaluating ethical concerns in planned emergency research involving critically ill patients: an interpretation of the guidance document from the United States Food and Drug Administration.

PubMed

Smischney, Nathan J; Onigkeit, James A; Hinds, Richard F; Nicholson, Wayne T

2015-01-01

U.S. federal regulations require that certain ethical elements be followed to protect human research subjects. The location and clinical circumstances of a proposed research study can differ substantially and can have significant implications for these ethical considerations. Both the location and clinical circumstances are particularly relevant for research in intensive care units (ICUs), where patients are often unable to provide informed consent to participate in a proposed research intervention. Our goal is to elaborate on the updated 2013 U.S. Food and Drug Administration (FDA) guidance document regarding an exemption from the requirement of obtaining informed consent from patients or their surrogates and to address certain elements within that document, thereby assisting clinicians in developing a framework for emergency research in accordance with the regulatory bodies at their own institutions and in the United States. Review of the 2011 and updated FDA guidance document on exemption from informed consent. The current process of obtaining informed consent within ICUs needs to be revisited, especially for research in which timely informed consent is not likely. In particular, the process of obtaining informed consent may not be appropriate or even ethical for critically ill patients in extremis who require an intervention for which there is no current acceptable standard of care and clinical equipoise exists. We provide clinicians with a viewpoint that further elaborates on the FDA guidance document. The viewpoints provided herein are those of the authors and are therefore inherently limited by the personal views of a selected few. Other clinicians or researchers may not interpret the FDA guidelines in a similar manner. Moreover, the discussion of a guideline document is a limitation in and of itself. The guidelines set forth by the FDA are precisely that-guidelines. Therefore, they may not be followed as outlined in the guidance document within one's own institution. Our goal is that, by elaborating on the guidelines for planned research involving human subjects in the ICU, institutional regulatory bodies may gain a better understanding in drafting their own document when faced with a clinician or a researcher who wishes to conduct planned research in an ICU. We believe that the interpretations provided will allow clinicians to safely undertake planned research in ICUs without endangering the main tenets of ethical research involving human participants. This research is needed for the advancement of care in the critically ill. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

Trends in internet search activity, media coverage, and patient-centered health information after the FDA safety communications on surgical mesh for pelvic organ prolapse.

PubMed

Stone, Benjamin V; Forde, James C; Levit, Valerie B; Lee, Richard K; Te, Alexis E; Chughtai, Bilal

2016-11-01

In July 2011, the US Food and Drug Administration (FDA) issued a safety communication regarding serious complications associated with surgical mesh for pelvic organ prolapse, prompting increased media and public attention. This study sought to analyze internet search activity and news article volume after this FDA warning and to evaluate the quality of websites providing patient-centered information. Google Trends™ was utilized to evaluate search engine trends for the term "pelvic organ prolapse" and associated terms between 1 January 2004 and 31 December 2014. Google News™ was utilized to quantify the number of news articles annually under the term "pelvic organ prolapse." The search results for the term "pelvic organ prolapse" were assessed for quality using the Health On the Net Foundation (HON) certification. There was a significant increase in search activity from 37.42 in 2010 to 57.75 in 2011, at the time of the FDA communication (p = 0.021). No other annual interval had a statistically significant increase in search activity. The single highest monthly search activity, given the value of 100, was August 2011, immediately following the July 2011 notification, with the next highest value being 98 in July 2011. Linear regression analysis of news articles per year since the FDA communication revealed r 2  = 0.88, with a coefficient of 186. Quality assessment demonstrated that 42 % of websites were HON-certified, with .gov sites providing the highest quality information. Although the 2011 FDA safety communication on surgical mesh was associated with increased public and media attention, the quality of relevant health information on the internet remains of poor quality. Future quality assurance measures may be critical in enabling patients to play active roles in their own healthcare.

Surface Hold Advisor Using Critical Sections

NASA Technical Reports Server (NTRS)

Law, Caleb Hoi Kei (Inventor); Hsiao, Thomas Kun-Lung (Inventor); Mittler, Nathan C. (Inventor); Couluris, George J. (Inventor)

2013-01-01

The Surface Hold Advisor Using Critical Sections is a system and method for providing hold advisories to surface controllers to prevent gridlock and resolve crossing and merging conflicts among vehicles traversing a vertex-edge graph representing a surface traffic network on an airport surface. The Advisor performs pair-wise comparisons of current position and projected path of each vehicle with other surface vehicles to detect conflicts, determine critical sections, and provide hold advisories to traffic controllers recommending vehicles stop at entry points to protected zones around identified critical sections. A critical section defines a segment of the vertex-edge graph where vehicles are in crossing or merging or opposite direction gridlock contention. The Advisor detects critical sections without reference to scheduled, projected or required times along assigned vehicle paths, and generates hold advisories to prevent conflicts without requiring network path direction-of-movement rules and without requiring rerouting, rescheduling or other network optimization solutions.

Academic and Demographic Predictors of NCLEX-RN Pass Rates in First- and Second-Degree Accelerated BSN Programs.

PubMed

Kaddoura, Mahmoud A; Flint, Elizabeth P; Van Dyke, Olga; Yang, Qing; Chiang, Li-Chi

Relatively few studies have addressed predictors of first-attempt outcomes (pass-fail) on the National Council Licensure Examination-Registered Nurses (NCLEX-RN) for accelerated BSN programs. The purpose of this study was to compare potential predictors of NCLEX outcomes in graduates of first-degree accelerated (FDA; n=62) and second-degree accelerated (SDA; n=173) BSN programs sharing a common nursing curriculum. In this retrospective study, bivariate analyses and multiple logistic regression assessed significance of selected demographic and academic characteristics as predictors of NCLEX-RN outcomes. FDA graduates were more likely than SDA graduates to fail the NCLEX-RN (P=.0013). FDA graduates were more likely to speak English as a second or additional language (P<.0001), have lower end-of-program GPA and HESI Exit Exam scores (both P<.0001), and have a higher proportions of grades ≤ C (P=.0023). All four variables were significant predictors of NCLEX-RN outcomes within both FDA and SDA programs. The only significant predictors in adjusted logistic regression of NCLEX-RN outcome for the pooled FDA+SDA graduate sample were proportion of grades ≤ C (a predictor of NCLEX-RN failure) and HESI Exit Exam score (a predictor of passing NCLEX-RN). Grades of C or lower on any course may indicate inadequate mastery of critical NCLEX-RN content and increased risk of NCLEX-RN failure. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantifying tight-gas sandstone permeability via critical path analysis

USDA-ARS?s Scientific Manuscript database

Rock permeability has been actively investigated over the past several decades by the geosciences community. However, its accurate estimation still presents significant technical challenges, especially in spatially complex rocks. In this letter, we apply critical path analysis (CPA) to estimate perm...

Implications of path tolerance and path characteristics on critical vehicle manoeuvres

NASA Astrophysics Data System (ADS)

Lundahl, K.; Frisk, E.; Nielsen, L.

2017-12-01

Path planning and path following are core components in safe autonomous driving. Typically, a path planner provides a path with some tolerance on how tightly the path should be followed. Based on that, and other path characteristics, for example, sharpness of curves, a speed profile needs to be assigned so that the vehicle can stay within the given tolerance without going unnecessarily slow. Here, such trajectory planning is based on optimal control formulations where critical cases arise as on-the-limit solutions. The study focuses on heavy commercial vehicles, causing rollover to be of a major concern, due to the relatively high centre of gravity. Several results are obtained on required model complexity depending on path characteristics, for example, quantification of required path tolerance for a simple model to be sufficient, quantification of when yaw inertia needs to be considered in more detail, and how the curvature rate of change interplays with available friction. Overall, in situations where the vehicle is subject to a wide range of driving conditions, from good transport roads to more tricky avoidance manoeuvres, the requirements on the path following will vary. For this, the provided results form a basis for real-time path following.

Who's guarding what? A poststructural feminist analysis of gardasil discourses.

PubMed

Thompson, Marie

2010-03-01

In May 2006 the Gardasil vaccine was approved for implementation in the United States to prohibit the spread of four strains of the human papillomavirus (HPV) that can lead to cervical cancer. Through a poststructural feminist reading, I critique ideologies at play throughout the Food and Drug Administration (FDA) approval hearing for this vaccine. I explore the conditions that gave rise to the adoption of the Gardasil vaccine as evidenced in the hearing transcript, and probe contradictions between choices the FDA enacted for the feminine body with those recommendations from lead scientists of Merck that urged the inclusion of males in the vaccination process. Along the way, I respond to appeals from scholars to address matters of health policy formation and implementation as critical and underexplored dimensions of health communication. I offer a vision that makes way for proactive engagement of males in reproductive and sexual health, particularly as the FDA delayed vaccine approval for males until 2009.

Introduction to HACCP.

USDA-ARS?s Scientific Manuscript database

The Hazard Analysis and Critical Control Point (HACCP) food safety inspection program is utilized by both USDA Food Safety Inspection Service (FSIS) and FDA for many of the products they regulate. This science-based program was implemented by the USDA FSIS to enhance the food safety of meat and pou...

FDA perspective on objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia.

PubMed

Kumar, Allison; Brooks, Steven S; Cavanaugh, Kenneth; Zuckerman, Bram

2009-12-01

The article by Conte et al.(1) on behalf of the Society for Vascular Surgery (SVS) in this issue of the Journal of Vascular Surgery provides guidelines for improving the consistency and interpretability of clinical trials intended to evaluate treatment options for patients with critical limb ischemia (CLI). This article identifies a number of key challenges with conducting and comparing CLI trials, including the wide spectrum of clinical presentations that CLI encompasses, the use of disparate eligibility criteria and endpoint measurements, and logistical and economic considerations that can limit study initiation and completion. The authors propose definitions for a number of performance goals derived from historical surgical literature as a means of reducing the negative impact of these factors. The current editorial reviews aspects of this proposal from the perspective of the authors in terms of their understanding of the statutory obligations of the U.S. Food and Drug Administration (FDA) to regulate the marketing of cardiovascular devices based on valid scientific evidence.

Office of Biological and Physical Research: Overview Transitioning to the Vision for Space Exploration

NASA Technical Reports Server (NTRS)

Crouch, Roger

2004-01-01

Viewgraphs on NASA's transition to its vision for space exploration is presented. The topics include: 1) Strategic Directives Guiding the Human Support Technology Program; 2) Progressive Capabilities; 3) A Journey to Inspire, Innovate, and Discover; 4) Risk Mitigation Status Technology Readiness Level (TRL) and Countermeasures Readiness Level (CRL); 5) Biological And Physical Research Enterprise Aligning With The Vision For U.S. Space Exploration; 6) Critical Path Roadmap Reference Missions; 7) Rating Risks; 8) Current Critical Path Roadmap (Draft) Rating Risks: Human Health; 9) Current Critical Path Roadmap (Draft) Rating Risks: System Performance/Efficiency; 10) Biological And Physical Research Enterprise Efforts to Align With Vision For U.S. Space Exploration; 11) Aligning with the Vision: Exploration Research Areas of Emphasis; 12) Code U Efforts To Align With The Vision For U.S. Space Exploration; 13) Types of Critical Path Roadmap Risks; and 14) ISS Human Support Systems Research, Development, and Demonstration. A summary discussing the vision for U.S. space exploration is also provided.

76 FR 41266 - Critical Path Manufacturing Sector Research Initiative (U01)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-13

... under the ``Regulatory Information'' section. The title of the page is ``Research Acquisitions... the Critical Path. Research into methods for laboratory synthesis of molecules that have been designed... accelerated by better design of the facilities where this research is conducted. Creating and making these...

FDA marketing claims, and the practitioner.

PubMed

Runner, Susan

2006-03-01

The Food and Drug Administration (FDA) is the federal agency that is tasked with regulating market entry for medical devices. The laws that govern this process are codified in the Federal Food Drug and Cosmetic Act (the Act) and the regulations are based on this law. The medical device amendments to the Act were instituted in 1976, instituting the methods for classification of medical devices and the format for the premarket review of devices. Information for practitioners on how medical devices come to market, what data are required, how specific claims are cleared, and how the practitioner can give input to the system are critical for the further development of safe and effective medical devices.

Establishment of a public docket for medical device/radiological health policy statements and operating procedure guides--FDA. Notice.

PubMed

1993-07-27

The Food and Drug Administration (FDA) is announcing that it is establishing a public docket for policy speeches, policy statements, and standard operating procedure guides pertaining to product evaluation and regulatory enforcement for its medical device and radiological health programs. The docket will operate on a 1-year trial basis and will serve both as a repository for critical policy documents generated by the Center for Devices and Radiological Health (CDRH) and as a public display mechanism for access by representatives of the industry and other interested persons. This action is one element of an overall communications initiative to ensure uniform and timely access to important information.

The principles of HACCP.

USDA-ARS?s Scientific Manuscript database

The Hazard Analysis and Critical Control Point (HACCP) food safety inspection program is utilized by both USDA Food Safety Inspection Service (FSIS) and FDA for many of the products they regulate. This science-based program was implemented by the USDA FSIS to enhance the food safety of meat and pou...

Prescription Patterns for Tigecycline in Severely Ill Patients for Non-FDA Approved Indications in a Developing Country: A Compromised Outcome

PubMed Central

Moghnieh, Rima A.; Abdallah, Dania I.; Fawaz, Ismail A.; Hamandi, Tarek; Kassem, Mohammad; El-Rajab, Nabila; Jisr, Tamima; Mugharbil, Anas; Droubi, Nabila; Al Tabah, Samaa; Sinno, Loubna; Ziade, Fouad; Daoud, Ziad; Ibrahim, Ahmad

2017-01-01

Introduction: With the rise in antibiotic resistance, tigecycline has been used frequently in off-label indications, based on its in-vitro activity against multidrug-resistant organisms. In this study, our aim was to assess its use in approved and unapproved indications. Materials and Methods: This is a retrospective chart review evaluating a 2-year experience of tigecycline use for > 72 h in 153 adult patients inside and outside critical care unit from January 2012 to December 2013 in a Lebanese tertiary-care hospital. Results: Tigecycline was mostly used in off-label indications (81%) and prescribed inside the critical care area, where the number of tigecycline cycles was 16/1,000 patient days. Clinical success was achieved in 43.4% of the patients. In the critically ill group, it was significantly higher in patients with a SOFA score <7 using multivariate analysis (Odds Ratio (OR) = 12.51 [4.29–36.51], P < 0.0001). Microbiological success was achieved in 43.3% of patients. Yet, the univariate and adjusted multivariate models failed to show a significant difference in this outcome between patients inside vs. outside critical care area, those with SOFA score <7 vs. ≥ 7, and in FDA-approved vs. off-label indications. Total mortality reached ~45%. It was significantly higher in critically ill patients with SOFA score ≥7 (OR = 5.17 [2.43–11.01], P < 0.0001) and in off-label indications (OR = 4.00 [1.30–12.31], P = 0.01) using an adjusted multivariate model. Gram-negative bacteria represented the majority of the clinical isolates (81%) and Acinetobacter baumannii predominated (28%). Carbapenem resistance was present in 85% of the recovered Acinetobacter, yet, more than two third of the carbapenem-resistant Acinetobacter species were still susceptible to tigecycline. Conclusion: In our series, tigecycline has been mostly used in off-label indications, specifically in severely ill patients. The outcome of such infections was not inferior to that of FDA-approved indications, especially inside critical care area. The use of this last resort antibiotic in complicated clinical scenarios with baseline microbiological epidemiology predominated by extensively-drug resistant pathogens ought to be organized. PMID:28396656

Conceptualizing the Critical Path Linked by Teacher Commitment

ERIC Educational Resources Information Center

Sun, Jingping

2015-01-01

Purpose: The purpose of this paper is to propose a critical path through which school leadership travels to students by highlighting the importance of teacher commitment. Design/methodology/approach: Using both meta-analytic and narrative review methods, this paper systematically reviews the evidence in the past 20 years about the…

THE CRITICAL-PATH METHOD OF CONSTRUCTION CONTROL.

ERIC Educational Resources Information Center

DOMBROW, RODGER T.; MAUCHLY, JOHN

THIS DISCUSSION PRESENTS A DEFINITION AND BRIEF DESCRIPTION OF THE CRITICAL-PATH METHOD AS APPLIED TO BUILDING CONSTRUCTION. INTRODUCING REMARKS CONSIDER THE MOST PERTINENT QUESTIONS PERTAINING TO CPM AND THE NEEDS ASSOCIATED WITH MINIMIZING TIME AND COST ON CONSTRUCTION PROJECTS. SPECIFIC DISCUSSION INCLUDES--(1) ADVANTAGES OF NETWORK TECHNIQUES,…

Assessment of critical path analyses of the relationship between permeability and electrical conductivity of pore networks

USDA-ARS?s Scientific Manuscript database

Critical path analysis (CPA) is a method for estimating macroscopic transport coefficients of heterogeneous materials that are highly disordered at the micro-scale. Developed originally to model conduction in semiconductors, numerous researchers have noted that CPA might also have relevance to flow ...

EPA Critical Path Science Plan Projects 19, 20 and 21: Human and Bovine Source Detection

EPA Science Inventory

The U.S. EPA Critical Path Science Plan Projects are: Project 19: develop novel bovine and human host-specific PCR assays and complete performance evaluation with other published methods. Project 20: Evaluate human-specific assays with water samples impacted with different lev...

Ensuring critical event sequences in high consequence computer based systems as inspired by path expressions

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

Kidd, M.E.C.

1997-02-01

The goal of our work is to provide a high level of confidence that critical software driven event sequences are maintained in the face of hardware failures, malevolent attacks and harsh or unstable operating environments. This will be accomplished by providing dynamic fault management measures directly to the software developer and to their varied development environments. The methodology employed here is inspired by previous work in path expressions. This paper discusses the perceived problems, a brief overview of path expressions, the proposed methods, and a discussion of the differences between the proposed methods and traditional path expression usage and implementation.

75 FR 40839 - Agency Information Collection Activities; Proposed Collection; Comment Request; Hazard Analysis...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0357] Agency Information Collection Activities; Proposed Collection; Comment Request; Hazard Analysis and Critical Control Point Procedures for the Safe and Sanitary Processing and Importing of Juice AGENCY: Food...

Generating Performance Models for Irregular Applications

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

Friese, Ryan D.; Tallent, Nathan R.; Vishnu, Abhinav

2017-05-30

Many applications have irregular behavior --- non-uniform input data, input-dependent solvers, irregular memory accesses, unbiased branches --- that cannot be captured using today's automated performance modeling techniques. We describe new hierarchical critical path analyses for the \\Palm model generation tool. To create a model's structure, we capture tasks along representative MPI critical paths. We create a histogram of critical tasks with parameterized task arguments and instance counts. To model each task, we identify hot instruction-level sub-paths and model each sub-path based on data flow, instruction scheduling, and data locality. We describe application models that generate accurate predictions for strong scalingmore » when varying CPU speed, cache speed, memory speed, and architecture. We present results for the Sweep3D neutron transport benchmark; Page Rank on multiple graphs; Support Vector Machine with pruning; and PFLOTRAN's reactive flow/transport solver with domain-induced load imbalance.« less

The role of critical ethnic awareness and social support in the discrimination-depression relationship among Asian Americans: path analysis.

PubMed

Kim, Isok

2014-01-01

This study used a path analytic technique to examine associations among critical ethnic awareness, racial discrimination, social support, and depressive symptoms. Using a convenience sample from online survey of Asian American adults (N = 405), the study tested 2 main hypotheses: First, based on the empowerment theory, critical ethnic awareness would be positively associated with racial discrimination experience; and second, based on the social support deterioration model, social support would partially mediate the relationship between racial discrimination and depressive symptoms. The result of the path analysis model showed that the proposed path model was a good fit based on global fit indices, χ²(2) = 4.70, p = .10; root mean square error of approximation = 0.06; comparative fit index = 0.97; Tucker-Lewis index = 0.92; and standardized root mean square residual = 0.03. The examinations of study hypotheses demonstrated that critical ethnic awareness was directly associated (b = .11, p < .05) with the racial discrimination experience, whereas social support had a significant indirect effect (b = .48; bias-corrected 95% confidence interval [0.02, 1.26]) between the racial discrimination experience and depressive symptoms. The proposed path model illustrated that both critical ethnic awareness and social support are important mechanisms for explaining the relationship between racial discrimination and depressive symptoms among this sample of Asian Americans. This study highlights the usefulness of the critical ethnic awareness concept as a way to better understand how Asian Americans might perceive and recognize racial discrimination experiences in relation to its mental health consequences.

Pilot projects for improving product tracing along the food supply system.

PubMed

Bhatt, Tejas; Hickey, Caitlin; McEntire, Jennifer C

2013-12-01

In September 2011, the U.S. Food and Drug Administration (FDA) asked the Institute of Food Technologists (IFT) to execute product tracing pilot projects as described in Section 204 of the FDA Food Safety Modernization Act (FSMA). IFT collaborated with representatives from more than 100 organizations-including the U.S. Dept. of Agriculture, state departments of agriculture and public health, industry, and consumer groups, as well as not-for-profit organizations-to implement the pilots. The objectives of the pilot projects were 1) to identify and gather information on methods to improve product tracing of foods in the supply chain and 2) to explore and evaluate methods to rapidly and effectively identify the recipient of food to prevent or mitigate a foodborne illness outbreak and to address credible threats of serious adverse health consequences or death to humans or animals as a result of such food being adulterated or misbranded. IFT conducted evaluations to determine the impact of currently available technologies, types of data and formats, and the data acquisition process, as well as the use of technology on the ability to follow product movement through the supply chain. Results from the pilots found inconsistencies in the terminology, numbering systems, formatting, legibility, and occasionally the language that sometimes required IFT to contact the submitting firm to gain clarity, thus increasing the time required to capture data before any meaningful analysis could begin. However, the pilot participants appeared to have many of the tools and processes in place which are required to allow the capture and communication of critical track and trace information (such as, key data elements) at critical points of product transfer and transformation (such as, critical tracking events). IFT determined that costs associated with implementing a product tracing system can vary widely as determined by numerous factors: the size of the firm/facility, the method of product tracing already in use (manual or electronic), and the range of each firm's capabilities to implement or improve its product tracing system, to name a few. IFT found that there are several areas (such as uniformity and standardization, improved recordkeeping, enhanced planning and preparedness, better coordination and communication, and the use of technology) in which industry improvements and enhancements to FDA's processes would enable tracebacks and traceforwards to occur more rapidly. IFT developed 10 recommendations for FDA to consider for improving the state of system-wide food product tracing. The recommendations outlined in the report will enable FDA to conduct more rapid and effective investigations during foodborne illness outbreaks and other product tracing investigations, thus significantly enhancing protection of public health. © 2013 Institute of Food Technologists®

Update on the College of American Pathologists Experience With High-Risk Human Papillomavirus Proficiency Testing for Cytology.

PubMed

Ghofrani, Mohiedean; Zhao, Chengquan; Davey, Diane D; Fan, Fang; Husain, Mujtaba; Laser, Alice; Ocal, Idris T; Shen, Rulong Z; Goodrich, Kelly; Souers, Rhona J; Crothers, Barbara A

2016-12-01

- Since 2008, the College of American Pathologists has provided the human papillomavirus for cytology laboratories (CHPV) proficiency testing program to help laboratories meet the requirements of the Clinical Laboratory Improvement Amendments of 1988. - To provide an update on trends in proficiency testing performance in the College of American Pathologists CHPV program during the 4-year period from 2011 through 2014 and to compare those trends with the preceding first 3 years of the program. - Responses of laboratories participating in the CHPV program from 2011 through 2014 were analyzed using a nonlinear mixed model to compare different combinations of testing medium and platform. - In total, 818 laboratories participated in the CHPV program at least once during the 4 years, with participation increasing during the study period. Concordance of participant responses with the target result was more than 98% (38 280 of 38 892). Overall performance with all 3 testing media-ThinPrep (Hologic, Bedford, Massachusetts), SurePath (Becton, Dickinson and Company, Franklin Lakes, New Jersey), or Digene (Qiagen, Valencia, California)-was equivalent (P = .51), and all 4 US Food and Drug Administration (FDA)-approved platforms-Hybrid Capture 2 (Qiagen), Cervista (Hologic), Aptima (Hologic), and cobas (Roche Molecular Systems, Pleasanton, California)-outperformed laboratory-developed tests, unspecified commercial kits, and other (noncommercial) methods in ThinPrep medium (P < .001). However, certain off-label combinations of platform and medium, most notably Cervista with SurePath, demonstrated suboptimal performance (P < .001). - Laboratories demonstrated proficiency in using various combinations of testing media and platforms offered in the CHPV program, with statistically significant performance differences in certain combinations. These observations may be relevant in the current discussions about FDA oversight of laboratory-developed tests.

FDA preemption of drug and device labeling: who should decide what goes on a drug label?

PubMed

Valoir, Tamsen; Ghosh, Shubha

2011-01-01

The Supreme Court decided an issue that is critical to consumer health and safety last year. In April 2009, the Supreme Court held that extensive FDA regulation of drugs did not preempt a state law claim that an additional warning on the label was necessary to make the drug reasonably safe for use. Thus, states--and even courts and juries--are now free to cast their vote on what a drug label should say. This is in direct contrast to medical devices, where the federal statute regulating medical devices expressly provides that state regulations are preempted. This Article discusses basic preemption principles and drugs, and explores the policy ramifications of pro- and anti-preemption policy in the healthcare industry.

Healthcare software assurance.

PubMed

Cooper, Jason G; Pauley, Keith A

2006-01-01

Software assurance is a rigorous, lifecycle phase-independent set of activities which ensure completeness, safety, and reliability of software processes and products. This is accomplished by guaranteeing conformance to all requirements, standards, procedures, and regulations. These assurance processes are even more important when coupled with healthcare software systems, embedded software in medical instrumentation, and other healthcare-oriented life-critical systems. The current Food and Drug Administration (FDA) regulatory requirements and guidance documentation do not address certain aspects of complete software assurance activities. In addition, the FDA's software oversight processes require enhancement to include increasingly complex healthcare systems such as Hospital Information Systems (HIS). The importance of complete software assurance is introduced, current regulatory requirements and guidance discussed, and the necessity for enhancements to the current processes shall be highlighted.

How are drugs approved? Part 1: the evolution of the Food and Drug Administration.

PubMed

Howland, Robert H

2008-01-01

The discovery, development, and marketing of drugs for clinical use is a process that is complex, arduous, expensive, highly regulated, often criticized, and sometimes controversial. In the United States, the Food and Drug Administration (FDA) is the governmental agency responsible for regulating the development and marketing of drugs, medical devices, biologics, foods, cosmetics, radiation-emitting electronic devices, and veterinary products, with the objective of ensuring their safety and efficacy. As part of a broad overview of the drug development process, this article will describe the historical evolution of the FDA. This will provide background for two subsequent articles in this series, which will describe the ethical foundations of clinical research and hethe stages of drug development.

The safety and regulation of natural products used as foods and food ingredients.

PubMed

Abdel-Rahman, Ali; Anyangwe, Njwen; Carlacci, Louis; Casper, Steve; Danam, Rebecca P; Enongene, Evaristus; Erives, Gladys; Fabricant, Daniel; Gudi, Ramadevi; Hilmas, Corey J; Hines, Fred; Howard, Paul; Levy, Dan; Lin, Ying; Moore, Robert J; Pfeiler, Erika; Thurmond, T Scott; Turujman, Saleh; Walker, Nigel J

2011-10-01

The use of botanicals and dietary supplements derived from natural substances as an adjunct to an improved quality of life or for their purported medical benefits has become increasingly common in the United States. This review addresses the safety assessment and regulation of food products containing these substances by the U.S. Food and Drug Administration (FDA). The issue of safety is particularly critical given how little information is available on the toxicity of some of these products. The first section uses case studies for stevia and green tea extracts as examples of how FDA evaluates the safety of botanical and herbal products submitted for consideration as Generally Recognized as Safe under the Federal Food, Drug, and Cosmetics Act. The 1994 Dietary Supplement Health Education Act (DSHEA) created a regulatory framework for dietary supplements. The article also discusses the regulation of this class of dietary supplements under DSHEA and addresses the FDA experience in analyzing the safety of natural ingredients described in pre-market safety submissions. Lastly, we discuss an ongoing interagency collaboration to conduct safety testing of nominated dietary supplements.

Steady Increase In Prices For Oral Anticancer Drugs After Market Launch Suggests A Lack Of Competitive Pressure.

PubMed

Bennette, Caroline S; Richards, Catherine; Sullivan, Sean D; Ramsey, Scott D

2016-05-01

The cost of treating cancer has risen to unprecedented heights, putting tremendous financial pressure on patients, payers, and society. Previous studies have documented the rising prices of cancer drugs at launch, but less critical attention has been paid to the cost of these drugs after launch. We used pharmacy claims for commercially insured individuals to examine trends in postlaunch prices over time for orally administered anticancer drugs recently approved by the Food and Drug Administration (FDA). In the period 2007-13, inflation-adjusted per patient monthly drug prices increased 5 percent each year. Certain market changes also played a role, with prices rising an additional 10 percent with each supplemental indication approved by the FDA and declining 2 percent with the FDA's approval of a competitor drug. Our findings suggest that there is currently little competitive pressure in the oral anticancer drug market. Policy makers who wish to reduce the costs of anticancer drugs should consider implementing policies that affect prices not only at launch but also later. Project HOPE—The People-to-People Health Foundation, Inc.

Time-Critical Cooperative Path Following of Multiple UAVs: Case Studies

DTIC Science & Technology

2012-10-30

control algorithm for UAVs in 3D space. Section IV derives a strategy for time-critical cooperative path following of multiple UAVs that relies on the...UAVs in 3D space, in which a fleet of UAVs is tasked to converge to and follow a set of desired feasible paths so as to meet spatial and temporal...cooperative trajectory generation is not addressed in this paper. In fact, it is assumed that a set of desired 3D time trajectories pd,i(td) : R → R3

Toys and confectionery--a legally hazardous combination?

PubMed

Eldred, J S; Pape, S M

1998-01-01

"What kind of magic has Nestlé worked on FDA?" Many in the confectionery business were asking this very question after seeing the company introduce onto the market in July 1997 - without any immediate agency intervention - a chocolate product surrounding an inedible plastic sphere enclosing a toy, bearing the moniker Nestlé Magic(R). A spate of recent publicity 1 on the controversy engendered by the new product has focused public attention on a little-known provision of the Federal Food, Drug, and Cosmetic Act (FDCA), specifically section 402(d)(1). Adding fuel to the proverbial regulatory fire was the Food and Drug Administration's (FDA's) signaling of a possible reversal of its long-standing policy prohibiting the marketing of combination "confectionery and toy" products that contain nonfunctional, nonnutritive objects. After the product was launched, FDA, in response to a petition filed by Nestlé USA, stated its intention to 1) issue a guidance document that would purport to sanction such products on an interim basis, and 2) promulgate a regulation setting safety standards for such products and thereby authorize their marketing. Although Nestlé subsequently announced its withdrawal of the product,2 questions remain about the applicable law and FDA's authority. This article critically examines the agency's authority to authorize marketing of such products through a regulation that addresses the criteria set forth in section 402(d)(1).

76 FR 4918 - Agency Information Collection Activities; Announcement of Office of Management and Budget...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0357...; Hazard Analysis and Critical Control Point Procedures for the Safe and Sanitary Processing and Importing of Juice AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

78 FR 47701 - Agency Information Collection Activities; Proposed Collection; Comment Request; Procedures for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-06

... Fishery Products--21 CFR Part 123 (OMB Control Number 0910-0354)-- Extension FDA regulations in part 123 (21 CFR part 123) mandate the application of hazard analysis and critical control point (HACCP) principles to the processing of seafood. HACCP is a preventive system of hazard control designed to help...

75 FR 18211 - Agency Information Collection Activities; Proposed Collection; Comment Request; Procedures for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

... Importing of Fish and Fishery Products--21 CFR Part 123 (OMB Control Number 0910-0354)-- Extension FDA regulations in part 123 (21 CFR part 123) mandate the application of hazard analysis and critical control point (HACCP) principles to the processing of seafood. HACCP is a preventive system of hazard control...

Overview of regulation of dietary supplements in the USA and issues of adulteration with phenethylamines (PEAs).

PubMed

Pawar, Rahul S; Grundel, Erich

2017-03-01

The multi-billion dollar dietary supplement industry is global in reach. The industry has been criticized for problems related to poor quality control, safety, misbranding, and adulteration. In this review, we describe how the US Food and Drug Administration (FDA) regulates dietary supplements within the framework of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The Dietary Supplement Health and Education Act of 1994 (DSHEA), which amended the FD&C Act, gave the FDA the authority to promulgate Good Manufacturing Practices for dietary supplements and required that manufacturers provide the FDA information supporting a conclusion that the ingredients are reasonably expected to be safe if the dietary ingredients were not marketed in the USA before 15 October 1994. Recent amendments to the FD&C Act require that serious dietary-supplement-related adverse events be reported to the FDA and provide the agency with mandatory recall authority. We discuss the presence of naturally occurring (e.g. Ephedra, Citrus aurantium, Acacia) and synthetic (e.g. β-methylphenethylamines, methylsynephrine, α-ethyl-phenethylamine) biologically active phenethylamines (PEAs) in dietary supplements and of PEA drugs (e.g. clenbuterol, fenfluramine, sibutramine, lorcaserin) in weight-loss products. Regulatory actions against manufacturers of products labelled as dietary supplements that contain the aliphatic amines 1,3-dimethylamine and 1,3-dimethylbutylamine, and PEAs such as β-methylphenethylamine, aegeline, and Dendrobium illustrate the FDA's use of its authority under the FD&C Act to promote dietary supplement safety. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience.

PubMed

Goldkind, Lawrence; Laine, Loren

2006-04-01

Drug-induced hepatotoxicity is the leading cause of acute liver failure (ALF) in the US and the most common adverse event causing drug non-approval and drug withdrawal by the U.S. Food and Drug Administration (FDA). Three different nonsteroidal anti-inflammatory drugs (NSAIDs) have been withdrawn in the UK and/or the US due to hepatotoxicity (bromfenac, ibufenac, and benoxaprofen). A systematic review of clinical trials data for these drugs was performed in an effort to identify possible early signals that could have predicted post-marketing serious hepatoxicity. There were very limited published data on benoxaprofen and none on ibufenac or bromfenac. The publicly accessible archives of the FDA provided information on bromfenac. Flu-like symptoms associated with hepatic enzyme elevation and a case of possible drug-related hepatocellular jaundice may in retrospect have been signals for serious hepatotoxicity in the database of 1195 subjects reviewed by the FDA. Following approval, rates of acute liver failure for bromfenac were estimated to be in the range of 1:10 000. In addition, the safety databases of several drugs also accessed through FDA archives have been reviewed (simvastatin, tacrine, troglitazone, and ximelagatran). These data suggest that while ALT elevations alone do not reliably signal serious hepatotoxicity, elevated transaminases in association with symptomatic hepatitis or jaundice may be predictors of an increased risk of ALF. At present, however, pre-approval databases are generally not large enough to rule out low rates of serious hepatotoxicity. Therefore, it remains critical that clinicians report such cases to the FDA through the MEDWATCH system and that active post-marketing monitoring studies be used to identify potential rare cases of hepatotoxicity. Copyright (c) 2006 John Wiley & Sons, Ltd.

Software-Related Recalls of Health Information Technology and Other Medical Devices: Implications for FDA Regulation of Digital Health.

PubMed

Ronquillo, Jay G; Zuckerman, Diana M

2017-09-01

Policy Points: Medical software has become an increasingly critical component of health care, yet the regulation of these devices is inconsistent and controversial. No studies of medical devices and software assess the impact on patient safety of the FDA's current regulatory safeguards and new legislative changes to those standards. Our analysis quantifies the impact of software problems in regulated medical devices and indicates that current regulations are necessary but not sufficient for ensuring patient safety by identifying and eliminating dangerous defects in software currently on the market. New legislative changes will further deregulate health IT, reducing safeguards that facilitate the reporting and timely recall of flawed medical software that could harm patients. Medical software has become an increasingly critical component of health care, yet the regulatory landscape for digital health is inconsistent and controversial. To understand which policies might best protect patients, we examined the impact of the US Food and Drug Administration's (FDA's) regulatory safeguards on software-related technologies in recent years and the implications for newly passed legislative changes in regulatory policy. Using FDA databases, we identified all medical devices that were recalled from 2011 through 2015 primarily because of software defects. We counted all software-related recalls for each FDA risk category and evaluated each high-risk and moderate-risk recall of electronic medical records to determine the manufacturer, device classification, submission type, number of units, and product details. A total of 627 software devices (1.4 million units) were subject to recalls, with 12 of these devices (190,596 units) subject to the highest-risk recalls. Eleven of the devices recalled as high risk had entered the market through the FDA review process that does not require evidence of safety or effectiveness, and one device was completely exempt from regulatory review. The largest high-risk recall categories were anesthesiology and general hospital, with one each in cardiovascular and neurology. Five electronic medical record systems (9,347 units) were recalled for software defects classified as posing a moderate risk to patient safety. Software problems in medical devices are not rare and have the potential to negatively influence medical care. Premarket regulation has not captured all the software issues that could harm patients, evidenced by the potentially large number of patients exposed to software products later subject to high-risk and moderate-risk recalls. Provisions of the 21st Century Cures Act that became law in late 2016 will reduce safeguards further. Absent stronger regulations and implementation to create robust risk assessment and adverse event reporting, physicians and their patients are likely to be at risk from medical errors caused by software-related problems in medical devices. © 2017 Milbank Memorial Fund.

Regulatory challenges in manufacturing of pancreatic islets.

PubMed

Linetsky, E; Ricordi, C

2008-03-01

At the present time, transplantation of pancreatic islet cells is considered an experimental therapy for a selected cohort of patients with type 1 diabetes, and is conducted under an Investigational New Drug (IND) application. Encouraging results of the Edmonton Protocol published in the year 2000 sparked a renewed interest in clinical transplantation of allogeneic islets, triggering a large number of IND applications for phase I clinical trials. Promising results reported by a number of centers since then prompted the Food and Drug Administration (FDA) to consider the possibility of licensing allogeneic islets as a therapeutic treatment for patients with type 1 diabetes. However, prior to licensure, issues such as safety, purity, efficacy, and potency of the islet product must be addressed. This is complicated by the intricate nature of pancreatic islets and limited characterization prior to transplantation. In this context, control of the manufacturing process plays a critical role in the definition of the final product. Despite significant progress made in standardization of the donor organ preservation methods, reagents used, and characterization assays performed to qualify an islet cell product, control of the isolation process remains a challenge. Within the scope of the FDA regulations, islet cells meet the definition of a biologic product, somatic cell therapy, and a drug. In addition, AABB standards that address cellular therapy products apply to manufacturing facilities accredited by this organization. Control of the source material, isolation process, and final product are critical issues that must be addressed in the context of FDA and other relevant regulations applicable to islet cell products.

Do-It-Yourself Critical Path Method.

ERIC Educational Resources Information Center

Morris, Edward P., Jr.

This report describes the critical path method (CPM), a system for planning and scheduling work to get the best time-cost combination for any particular job. With the use of diagrams, the report describes how CPM works on a step-by-step basis. CPM uses a network to show which parts of a job must be done and how they would eventually fit together…

Pharmacotherapeutics of Intranasal Scopolamine: FDA Regulations and Procedures for Clinical Applications

NASA Technical Reports Server (NTRS)

Das, H.; Daniels, V. R.; Vaksman, Z.; Boyd, J. L.; Buckey, J. C.; Locke, J. P.; Putcha, L.

2007-01-01

Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during the early flight days of a space mission. Bioavailability of oral (PO) SMS medications is often low and highly variable; additionally, physiological changes in a microgravity environment exacerbate variability and decrease bioavailability. These factors prompted NASA to develop an intranasal dosage form of scopolamine (INSCOP) suitable for the treatment of SMS. However, to assure safety and efficacy of treatment in space, NASA physicians prescribe commercially available pharmaceutical products only. Development of a pharmaceutical preparation for clinical use must follow distinct clinical phases of testing, phase I through IV to be exact, before it can be approved by the FDA for approval for clinical use. After a physician sponsored Investigative New Drug (IND) application was approved by the FDA, a phase I clinical trial of INSCOP formulation was completed in normal human subjects and results published. The current project includes three phase II clinical protocols for the assessment of pharmacokinetics and pharmacodynamics (PK/PD), efficacy, and safety of INSCOP. Three clinical protocols that were submitted to FDA to accomplish the project objectives: 1) 002-A, a FDA Phase II dose ranging study with four dose levels between 0.1 and 0.4 mg in 12 subjects to assess PK/PD, 2) 002-B, a phase II clinical efficacy study in eighteen healthy subjects to compare efficacy of 0.2 (low dose) and 0.4 mg (high dose) INSCOP for prophylactic treatment of motion-induces (off-axis vertical rotation) symptoms, and (3) 002-C, a phase II clinical study with twelve subjects to determine bioavailability and pharmacodynamics of two doses (0.2 and 0.4 mg) of INSCOP in simulated microgravity, antiorthostatic bedrest. All regulatory procedures were competed that include certification for Good laboratory Procedures by Theradex , clinical documentation, personnel training, selection of clinical research operations contractor, data capturing and management, and annual reporting of results to FDA were successfully completed. Protocol 002-A was completed and sample and data analysis is currently in progress. Protocol 002-B is currently in progress at Dartmouth Hitchcock Medical Center and Protocol 002-C has been submitted to the FDA and will be implemented at the same contractor site as 002-A. An annual report was filed as required by FDA on the results of Protocol 002-A. Once all the three Phase II protocols are completed, a New Drug Administration application will be filed with FDA for Phase III clinical assessment and approval for marketing of the formulation. A commercial vendor will be identified for this phase. This is critical for making this available for treatment of SMS in astronauts and military personnel on duty. Once approved by FDA, INSCOP can be also used by civilian population for motion sickness associated with recreational travel and other ailments that require treatment with anticholinergic drugs.

The role of quantitative safety evaluation in regulatory decision making of drugs.

PubMed

Chakravarty, Aloka G; Izem, Rima; Keeton, Stephine; Kim, Clara Y; Levenson, Mark S; Soukup, Mat

2016-01-01

Evaluation of safety is a critical component of drug review at the US Food and Drug Administration (FDA). Statisticians are playing an increasingly visible role in quantitative safety evaluation and regulatory decision-making. This article reviews the history and the recent events relating to quantitative drug safety evaluation at the FDA. The article then focuses on five active areas of quantitative drug safety evaluation and the role Division of Biometrics VII (DBVII) plays in these areas, namely meta-analysis for safety evaluation, large safety outcome trials, post-marketing requirements (PMRs), the Sentinel Initiative, and the evaluation of risk from extended/long-acting opioids. This article will focus chiefly on developments related to quantitative drug safety evaluation and not on the many additional developments in drug safety in general.

Optimizing Department of Defense Acquisition Development Test and Evaluation Scheduling

DTIC Science & Technology

2015-06-01

CPM Critical Path Method DOD Department of Defense DT&E development test and evaluation EMD engineering and manufacturing development GAMS...these, including the Program Evaluation Review Technique (PERT), the Critical Path Method ( CPM ), and the resource- constrained project-scheduling...problem (RCPSP). These are of particular interest to this thesis as the current scheduling method uses elements of the PERT/ CPM , and the test

CPM (Critical Path Method) as a Curriculum Tool.

ERIC Educational Resources Information Center

Mongerson, M. Duane

This document discusses and illustrates the use of the Critical Path Method (CPM) as a tool for developing curriculum. In so doing a brief review of the evolution of CPM as a management tool developed by E. I. duPont de Nemours Company is presented. It is also noted that CPM is only a method of sequencing learning activities and not an end unto…

Defining Advancement Career Paths and Succession Plans: Critical Human Capital Retention Strategies for High-Performing Advancement Divisions

ERIC Educational Resources Information Center

Croteau, Jon Derek; Wolk, Holly Gordon

2010-01-01

There are many factors that can influence whether a highly talented staff member will build a career within an institution or use it as a stepping stone. This article defines and explores the notions of developing career paths and succession planning and why they are critical human capital investment strategies in retaining the highest performers…

Germany's ECEC Workforce: A Difficult Path to Professionalisation

ERIC Educational Resources Information Center

Rauschenbach, Thomas; Riedel, Birgit

2016-01-01

In a European comparison, the childcare profession in Germany has taken a distinct path of development which is closely interwoven with the history of early childhood education and care (ECEC) in general. Institutional choices critical to this path are the assignment of childcare as part of social welfare, the pursuit of a maternalist tradition in…

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

PubMed

Rodwin, Marc A

2013-01-01

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

Patient autonomy and the regulation of direct-to-consumer advertising.

PubMed

Zachry, W M; Ginsburg, D B

2001-12-01

The current direction of the US Food and Drug Administration (FDA) policy on direct-to-consumer advertising (DTCA) of pharmaceuticals is a subject of debate. The literature addresses the benefits and drawbacks of DTCA, but the foundations for such policies have not been investigated in detail. This paper explores the most recent FDA guidance on broadcast DTCA based on a critical examination of the principle of autonomy. Autonomy is determined not by the ability to choose a therapy, but by the ability to actively participate in choices about health care. DTCA can be an effective tool to increase patient awareness of their therapeutic choices, encourage patients to seek more information, and help them draw closer to autonomous choices, but only if the presentations provide fair and balanced information on the benefits and risks of therapy.

The selling of olestra.

PubMed

Nestle, M

1998-01-01

The Procter & Gamble Company spent 30 years and an estimated $500 million to bring its non-digestible fat substitute, olestra, to market. The Food and Drug Administration approved olestra as a food additive but requires products containing olestra to carry a warning statement about its potential effects on gastrointestinal function. In obtaining approval for olestra, P&G conducted a lengthy, persistent, and comprehensive campaign to enlist support from members of Congress; FDA staff; and food, nutrition, and health professionals. This campaign raises larger questions about corporate influence on government policies, and the relationships of corporations to health professionals. To address these larger concerns, the author reviews the history of olestra's approval; describes P&G's campaign to obtain support from FDA and Congress, to defend olestra against critics, and to market it to professionals, the press, and consumers; and suggests implications for public health policies.

Food from cloned animals is part of our brave old world.

PubMed

Miller, Henry I

2007-05-01

When confronted by pressure from activists and Congress, the US Food and Drug Administration (FDA) has not always adopted policies and made decisions about individual products that accord with the scientific evidence. An example was the unnecessarily and markedly prolonged review of the veterinary drug bovine somatotropin (bST), or bovine growth hormone, during the 1980s. The FDA now faces a similar situation surrounding the question of whether meat and milk from cloned animals and their offspring are safe for human consumption. Having made a preliminary decision in the affirmative - based on an exhaustive analysis of scientific articles, health records, blood samples and studies of the composition of meat and milk - the agency has been beleaguered by criticisms. It remains to be seen whether, ultimately, science will trump anti-technology, anti-consumer activism.

Teaching as a Political Act: Critical Pedagogy in Library Instruction

ERIC Educational Resources Information Center

Fritch, Melia Erin

2018-01-01

This article establishes a theoretical framework for critical library instruction (and thereby critical information literacy) that is built upon critical feminist theory, critical race theory, and engaged pedagogy, among others. Using the ideas and work of theorists to create a path linking the ideas of critical analyses together, the author…

76 FR 20588 - FDA Food Safety Modernization Act: Focus on Preventive Controls for Facilities; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

.... FDA-2011-N-0251] FDA Food Safety Modernization Act: Focus on Preventive Controls for Facilities... comment. SUMMARY: The Food and Drug Administration (FDA) is announcing a public meeting entitled ``FDA... controls for facilities provisions of the recently enacted FDA Food Safety Modernization Act (FSMA). FDA is...

Drugs@FDA: FDA Approved Drug Products

MedlinePlus

... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

IDAAPM: integrated database of ADMET and adverse effects of predictive modeling based on FDA approved drug data.

PubMed

Legehar, Ashenafi; Xhaard, Henri; Ghemtio, Leo

2016-01-01

The disposition of a pharmaceutical compound within an organism, i.e. its Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) properties and adverse effects, critically affects late stage failure of drug candidates and has led to the withdrawal of approved drugs. Computational methods are effective approaches to reduce the number of safety issues by analyzing possible links between chemical structures and ADMET or adverse effects, but this is limited by the size, quality, and heterogeneity of the data available from individual sources. Thus, large, clean and integrated databases of approved drug data, associated with fast and efficient predictive tools are desirable early in the drug discovery process. We have built a relational database (IDAAPM) to integrate available approved drug data such as drug approval information, ADMET and adverse effects, chemical structures and molecular descriptors, targets, bioactivity and related references. The database has been coupled with a searchable web interface and modern data analytics platform (KNIME) to allow data access, data transformation, initial analysis and further predictive modeling. Data were extracted from FDA resources and supplemented from other publicly available databases. Currently, the database contains information regarding about 19,226 FDA approval applications for 31,815 products (small molecules and biologics) with their approval history, 2505 active ingredients, together with as many ADMET properties, 1629 molecular structures, 2.5 million adverse effects and 36,963 experimental drug-target bioactivity data. IDAAPM is a unique resource that, in a single relational database, provides detailed information on FDA approved drugs including their ADMET properties and adverse effects, the corresponding targets with bioactivity data, coupled with a data analytics platform. It can be used to perform basic to complex drug-target ADMET or adverse effects analysis and predictive modeling. IDAAPM is freely accessible at http://idaapm.helsinki.fi and can be exploited through a KNIME workflow connected to the database.Graphical abstractFDA approved drug data integration for predictive modeling.

Assessment of in vitro COPD models for tobacco regulatory science: Workshop proceedings, conclusions and paths forward for in vitro model use.

PubMed

Behrsing, Holger; Raabe, Hans; Manuppello, Joseph; Bombick, Betsy; Curren, Rodger; Sullivan, Kristie; Sethi, Sanjay; Phipps, Richard; Tesfaigzi, Yohannes; Yan, Sherwin; D'Ruiz, Carl; Tarran, Robert; Constant, Samuel; Phillips, Gary; Gaça, Marianna; Hayden, Patrick; Cao, Xuefei; Mathis, Carole; Hoeng, Julia; Braun, Armin; Hill, Erin

2016-05-01

The Family Smoking Prevention and Tobacco Control Act of 2009 established the Food and Drug Administration Center for Tobacco Products (FDA-CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed 'modified risk'. On 8-10 December 2014, IIVS organised a workshop conference, entitled Assessment of In Vitro COPD Models for Tobacco Regulatory Science, to bring together stakeholders representing regulatory agencies, academia, industry and animal protection, to address the research priorities articulated by the FDA-CTP. Specific topics were covered to assess the status of current in vitro technologies as they are applied to understanding the adverse pulmonary events resulting from tobacco product exposure, and in particular, the progression of chronic obstructive pulmonary disease (COPD). The four topics covered were: a) Inflammation and Oxidative Stress; b) Ciliary Dysfunction and Ion Transport; c) Goblet Cell Hyperplasia and Mucus Production; and d) Parenchymal/Bronchial Tissue Destruction and Remodelling. The 2.5 day workshop included 18 expert speakers, plus poster sessions, networking and breakout sessions, which identified key findings and provided recommendations to advance the in vitro technologies and assays used to evaluate tobacco-induced disease etiologies. The workshop summary was reported at the 2015 Society of Toxicology Annual Meeting, and the recommendations led to an IIVS-organised technical workshop in June 2015, entitled Goblet Cell Hyperplasia, Mucus Production, and Ciliary Beating Assays, to assess these assays and to conduct a proof-of-principle multi-laboratory exercise to determine their suitability for standardisation. Here, we report on the proceedings, recommendations and outcomes of the December 2014 workshop, including paths forward to continue the development of non-animal methods to evaluate tissue responses that model the disease processes that may lead to COPD, a major cause of mortality worldwide. 2016 FRAME.

Establishing Standards on Colors from Natural Sources.

PubMed

Simon, James E; Decker, Eric A; Ferruzzi, Mario G; Giusti, M Monica; Mejia, Carla D; Goldschmidt, Mark; Talcott, Stephen T

2017-11-01

Color additives are applied to many food, drug, and cosmetic products. With up to 85% of consumer buying decisions potentially influenced by color, appropriate application of color additives and their safety is critical. Color additives are defined by the U.S. Federal Food, Drug, and Cosmetic Act (FD&C Act) as any dye, pigment, or substance that can impart color to a food, drug, or cosmetic or to the human body. Under current U.S. Food and Drug Administration (FDA) regulations, colors fall into 2 categories as those subject to an FDA certification process and those that are exempt from certification often referred to as "natural" colors by consumers because they are sourced from plants, minerals, and animals. Certified colors have been used for decades in food and beverage products, but consumer interest in natural colors is leading market applications. However, the popularity of natural colors has also opened a door for both unintentional and intentional economic adulteration. Whereas FDA certifications for synthetic dyes and lakes involve strict quality control, natural colors are not evaluated by the FDA and often lack clear definitions and industry accepted quality and safety specifications. A significant risk of adulteration of natural colors exists, ranging from simple misbranding or misuse of the term "natural" on a product label to potentially serious cases of physical, chemical, and/or microbial contamination from raw material sources, improper processing methods, or intentional postproduction adulteration. Consistent industry-wide safety standards are needed to address the manufacturing, processing, application, and international trade of colors from natural sources to ensure quality and safety throughout the supply chain. © 2017 Institute of Food Technologists®.

Path Expressions

DTIC Science & Technology

1975-06-01

ORGANIZATION NAME AND ADDRESS Carnegie-Mellon University Computer Science Dept Pittsburgh, Pa 15213 II. CONTROLLING OFFICE NAMF AND ADDRESS...programmer. Example 1. A communciation between two procasses is initiated by declaring a buffer which can hold a message whose interpretation is Known...words, the functions named in a path are automatically embedded in a critical region specific for that path.) The computation of the next state in

Cyber Fighter Associate

DTIC Science & Technology

2016-01-01

accomplish a patch- management mission while securing a critical path. As a first proof of concept a simulation with a network of 10 nodes and 4...software-agility walk of the “PERFORMANCE Each Threat Managed ” tree is slightly more complex than the network -agility walk. The original design of the...CyFiA was tested to accomplish a patch- management mission while securing a critical path. As a first proof of concept a simulation with a network of 10

The effects of narrow and elevated path walking on aperture crossing.

PubMed

Hackney, Amy L; Cinelli, Michael E; Denomme, Luke T; Frank, James S

2015-06-01

The study investigated the impact that action capabilities have on identifying possibilities for action, particularly how postural threat influences the passability of apertures. To do this, the ability to maintain balance was challenged by manipulating the level of postural threat while walking. First, participants walked along a 7m path and passed through two vertical obstacles spaced 1.1-1.5×the shoulder width apart during normal walking. Next, postural threat was manipulated by having participants complete the task either walking on a narrow, ground level path or on an elevated/narrow path. Despite a decrease in walking speed as well as an increase in trunk sway in both the narrow and elevated/narrow walking conditions, the passability of apertures was only affected when the consequence of instability was greatest. In the elevated/narrow walking condition, individuals maintained a larger critical point (rotated their shoulders for larger aperture widths) compared to normal walking. However, this effect was not observed for the narrow path walking suggesting that the level of postural threat was not enough to impose similar changes to the critical point. Therefore, it appears that manipulating action capabilities by increasing postural threat does indeed influence aperture crossing behavior, however the consequence associated with instability must be high before both gait characteristics and the critical point are affected. Copyright © 2015 Elsevier B.V. All rights reserved.

In Praise of Ignorance

ERIC Educational Resources Information Center

Formica, Piero

2014-01-01

In this article Piero Formica examines the difference between incremental and revolutionary innovation, distinguishing between the constrained "path finders" and the unconstrained "path creators". He argues that an acceptance of "ignorance" and a willingness to venture into the unknown are critical elements in…

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

PubMed

2010-09-29

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

78 FR 19715 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1153] Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish Pilot Projects and...: The Food and Drug Administration (FDA) is extending the comment period for the notice entitled...

77 FR 14404 - Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2002-D-0094; (formerly Docket No. 02D-0049)] Guidance for the Public, Food and Drug Administration (FDA) Advisory... Food and Drug Administration (FDA) is announcing the availability of a guidance for the public, FDA...

78 FR 950 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-07

..., FDA- 2012-M-0965, FDA-2012-M-0968, FDA-2012-M-1011, and FDA-2012-M-1013] Medical Devices; Availability...\\ February 16, 2011. Adjustable Gastric Banding System. P100049, FDA-2012-M-0893....... Torax Medical, Inc.... Trabecular Micro- Bypass Stent and Inserter. P110007, FDA-2012-M-0734....... Abbott Medical Healon[supreg...

75 FR 76992 - Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: The Open Public Hearing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2005-D-0072] (formerly Docket No. 2005D-0042) Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: The Open Public Hearing at FDA Advisory Committee Meetings; Availability AGENCY: Food and Drug...

78 FR 14309 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1153] Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish Pilot Projects and... information. SUMMARY: In September 2011, the Food and Drug Administration (FDA or the Agency) asked the...

Zohydro approval by food and drug administration: controversial or frightening?

PubMed

Manchikanti, Laxmaiah; Atluri, Sairam; Candido, Kenneth D; Boswell, Mark V; Simopoulos, Thomas T; Grider, Jay S; Falco, Frank J E; Hirsch, Joshua A

2014-01-01

The actions and regulations of the Food and Drug Administration (FDA) are crucial to the entire population of the U.S., specifically the public who take a multitude of drugs and providers who prescribe drugs and devices. Further, the FDA is relevant to investors, specifically in regards to biotech and pharmaceutical companies involved in developing new drugs. The FDA has been criticized for a lack of independence on the one hand and excessive regulatory and expanding authority without evidence and consistency of the actions on the other hand. The FDA approved a single-entity, long-acting, hydrocodone product (Zohydro, Zogenix, San Diego, CA) on October 25, 2013, against the recommendation of the FDA's own appointed scientific advisory panel, which voted 11 to 2 against the approval of Zohydro. Subsequent to the approval, multiple consumer safety organizations, health care agencies, addiction treatment providers, professional organizations, and other groups on the frontline of the opioid addiction epidemic have expressed concern. In addition, the US Congress and various state attorneys general raised serious concerns about the approval of Zohydro, which is highly addictive and may enhance the opioid addiction epidemic. Supporters of Zohydro contend that it is necessary and essential to manage chronic pain and improve functional status with no additional risk. Over the past 15 years, prescriptions for opioids have skyrocketed with the United States consuming more than 84% of the global oxycodone and more than 99% of the hydrocodone supply. The sharp increase in opioid prescribing has led to parallel increases in opioid addiction and overdose deaths, surpassing motor vehicle injuries in the U.S. Recent studies assessing the trends of medical use and misuse of opioid analgesics from 2000 to 2011 have concluded that the present trend of the continued increase in the medical use of opioid analgesics appears to contribute to increasing misuse, resulting in multiple health consequences, despite numerous regulations enforced by multiple organizations. The approval of Zohydro and its defense from the FDA were based on a misunderstanding of the prevalence of chronic severe disabling pain. Based on inaccurate data from the Institute of Medicine, in part caused by conflicts of interest, 100 million persons have been described to suffer from severe pain - the correct number is 22.6 million. This manuscript analyzes 3 important principles of drug approval and utilization based on safety, efficacy, and medical necessity. Based on the limited literature that the authors were able to review including that which was submitted to the FDA by the manufacturers, it appears the safety, efficacy, and medical necessity were not demonstrated. In fact, the study submitted to the FDA showed a 50% pain improvement in only 48% of the patients in the treatment group and 21% of the patients in the placebo group at 85 day follow-up. This is a statistically significant result but its clinical relevance is unknown. The FDA approval decision occurring against the backdrop of the advisory panel recommendation is concerning and may result in serious consequences in the future.

Bioastronautics Roadmap: A Risk Reduction Strategy for Human Space Exploration

NASA Technical Reports Server (NTRS)

2005-01-01

The Bioastronautics Critical Path Roadmap is the framework used to identify and assess the risks to crews exposed to the hazardous environments of space. It guides the implementation of research strategies to prevent or reduce those risks. Although the BCPR identifies steps that must be taken to reduce the risks to health and performance that are associated with human space flight, the BCPR is not a "critical path" analysis in the strict engineering sense. The BCPR will evolve to accommodate new information and technology development and will enable NASA to conduct a formal critical path analysis in the future. As a management tool, the BCPR provides information for making informed decisions about research priorities and resource allocation. The outcome-driven nature of the BCPR makes it amenable for assessing the focus, progress and success of the Bioastronautics research and technology program. The BCPR is also a tool for communicating program priorities and progress to the research community and NASA management.

Advances in Induced Pluripotent Stem Cells, Genomics, Biomarkers, and Antiplatelet Therapy

PubMed Central

Barbato, Emanuele; Lara-Pezzi, Enrique; Stolen, Craig; Taylor, Angela; Barton, Paul J.; Bartunek, Jozef; Iaizzo, Paul; Judge, Daniel P.; Kirshenbaum, Lorrie; Blaxall, Burns C.; Terzic, Andre; Hall, Jennifer L.

2014-01-01

The Journal provides the clinician and scientist with the latest advances in discovery research, emerging technologies, pre-clinical research design and testing, and clinical trials. We highlight advances in areas of induced pluripotent stem cells, genomics, biomarkers, multi-modality imaging and antiplatelet biology and therapy. The top publications are critically discussed and presented along with anatomical reviews and FDA insight to provide context. PMID:24659088

The MicroMed DeBakey VAD

NASA Image and Video Library

2004-06-23

JSC2004-E-26519 --- Dr. Michael DeBakey (far right) observes preparation procedures before the implantation of a MicroMed DeBakey VAD® (ventricular assist device). The revolutionary heart pump received FDA approval in February 2004 for use in critically ill children awaiting heart transplants. The heart pump was designed with the help of NASA engineers who began working with Dr. DeBakey on the pump's development in the mid-1980s.

Pediatric post-marketing safety systems in North America: assessment of the current status.

PubMed

McMahon, Ann W; Wharton, Gerold T; Bonnel, Renan; DeCelle, Mary; Swank, Kimberley; Testoni, Daniela; Cope, Judith U; Smith, Phillip Brian; Wu, Eileen; Murphy, Mary Dianne

2015-08-01

It is critical to have pediatric post-marketing safety systems that contain enough clinical and epidemiological detail to draw regulatory, public health, and clinical conclusions. The pediatric safety surveillance workshop (PSSW), coordinated by the Food and Drug Administration (FDA), identified these pediatric systems as of 2010. This manuscript aims to update the information from the PSSW and look critically at the systems currently in use. We reviewed North American pediatric post-marketing safety systems such as databases, networks, and research consortiums found in peer-reviewed journals and other online sources. We detail clinical examples from three systems that FDA used to assess pediatric medical product safety. Of the 59 systems reviewed for pediatric content, only nine were pediatric-focused and met the inclusion criteria. Brief descriptions are provided for these nine. The strengths and weaknesses of three systems (two of the nine pediatric-focused and one including both children and adults) are illustrated with clinical examples. Systems reviewed in this manuscript have strengths such as clinical detail, a large enough sample size to capture rare adverse events, and/or a patient denominator internal to the database. Few systems include all of these attributes. Pediatric drug safety would be better informed by utilizing multiple systems to take advantage of their individual characteristics. Copyright © 2015 John Wiley & Sons, Ltd.

Perceptions of the Food and Drug Administration as a Tobacco Regulator

PubMed Central

Jarman, Kristen L.; Ranney, Leah M.; Baker, Hannah M.; Vallejos, Quirina M.; Goldstein, Adam O.

2017-01-01

Objectives The U. S. Food and Drug Administration (FDA) now has regulatory authority over all tobacco products. Little is known about public awareness and perceptions of FDA in their new role as a tobacco regulator. This research utilizes focus groups to examine perceptions of FDA as a tobacco regulator so that FDA can better communicate with the public about this role. Methods We conducted 6 focus groups in 2014 among a diverse sample of smokers and non-smokers. Participants were asked if they had heard of FDA, what they knew about FDA, if they associated FDA with tobacco, and their thoughts about this FDA role. Results A total of 41 individuals participated. Although nearly all participants had heard of FDA, most were not aware of FDA’s regulatory authority over tobacco products, did not associate the role of FDA with tobacco, and some drew comparisons between FDA’s work in tobacco and their work regulating food and drugs. Conclusion Data suggest that although public awareness of FDA regulatory authority over tobacco is low, with proper public education, the public may find FDA to be a trustworthy source of tobacco regulation. PMID:29051917

Clinical care paths: a role for finance in clinical decision-making.

PubMed

Abrams, Michael N; Cummings, Simone; Hage, Dana

2012-12-01

Care paths map the critical actions and decision points across a patient's course of medical treatment; their purpose is to guide physicians in the delivery of high-quality care while reducing care costs by avoiding services that do not contribute meaningfully to positive outcomes. Each care path development initiative should be led by a respected physician champion, whose specialty is in the area of the care episode being mapped, with the support of a clinician project manager. Once the care path has been developed and implemented, the finance leader's role begins in earnest with the tracking of financial and clinical data against care paths.

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

PubMed

Liang, Bryan A; Mackey, Tim K

2012-02-09

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

The evolving role of monoclonal antibodies in colorectal cancer: early presumptions and impact on clinical trial development.

PubMed

Eng, Cathy

2010-01-01

Targeted biologic agents have an established role in treating metastatic colorectal cancer (mCRC). Bevacizumab, a recombinant monoclonal antibody against the vascular endothelial growth factor ligand is approved by the U.S. Food and Drug Administration (FDA) for bevacizumab-naïve patients. Cetuximab, a chimeric monoclonal antibody (mAb) against the epidermal growth factor receptor (EGFR) is FDA approved as a single agent, or in combination with irinotecan, in both irinotecan-naïve and refractory patients, and has additional efficacy in combination with oxaliplatin. Panitumumab, a fully human EGFR mAb, is FDA approved as a single agent in refractory patients but has additional efficacy in combination with chemotherapy. After reaching a temporary therapeutic plateau of FDA-approved agents for the treatment of mCRC, pivotal results have developed that critically affect the care for these patients. Correlative data from randomized trials of EGFR inhibitors across disease settings have demonstrated higher response rates, specifically for patients with wild-type K-RAS tumors. The interpretation of the B-RAF mutation and other molecular markers may further define the appropriateness of anti-EGFR therapy. Recent literature revealed that the first-line use of combined anti-EGFR therapy plus bevacizumab resulted in inferior outcomes and additional toxicities. Furthermore, the role of biologic agents for locally advanced colon cancer cannot be advocated at this time. With impending changes in the health care system, the economic impact of mAbs will continue to be scrutinized. Hence, as the significance of molecular markers continues to develop, their role as it pertains to the appropriate use of biologic agents in the treatment of mCRC will continue to evolve.

Has the tobacco industry evaded the FDA's ban on ‘Light’ cigarette descriptors?

PubMed Central

Connolly, Gregory N; Alpert, Hillel R

2014-01-01

Background Under the Family Smoking Prevention and Tobacco Control Act (FSPTCA), the Food and Drug Administration (FDA) banned the use of “Lights” descriptors or similar terms on tobacco products that convey messages of reduced risk. Manufacturers eliminated terms explicitly stated and substituted colour name descriptors corresponding to the banned terms. This paper examines whether the tobacco industry complied with or circumvented the law and potential FDA regulatory actions. Methods Philip Morris retailer manuals, manufacturers' annual reports filed with the Massachusetts Department of Public Health, a national public opinion survey, and market-wide cigarette sales data were examined. Results Manufacturers substituted “Gold” for “Light” and “Silver” for “Ultra-light” in the names of Marlboro sub-brands, and “Blue”, “Gold”, and “Silver” for banned descriptors in sub-brand names. Percent filter ventilation levels, used to generate the smoke yield ranges associated with “Lights” categories, appear to have been reassigned to the new colour brand name descriptors. Following the ban, 92% of smokers reported they could easily identify their usual brands, and 68% correctly named the package colour associated with their usual brand, while sales for “Lights” cigarettes remained unchanged. Conclusions Tobacco manufacturers appear to have evaded a critical element of the FSPTCA, the ban on misleading descriptors that convey reduced health risk messages. The FPSTCA provides regulatory mechanisms, including banning these products as adulterated (Section 902). Manufacturers could then apply for pre-market approval as new products and produce evidence for FDA evaluation and determination whether or not sales of these products are in the public health interest. PMID:23485704

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

PubMed Central

Mackey, Tim K

2012-01-01

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

Food and Drug Administration (FDA) postmarket reported side effects and adverse events associated with pulmonary hypertension therapy in pediatric patients.

PubMed

Maxey, Dawn M; Ivy, D Dunbar; Ogawa, Michelle T; Feinstein, Jeffrey A

2013-10-01

Because most medications for pediatric pulmonary hypertension (PH) are used off label and based on adult trials, little information is available on pediatric-specific adverse events (AEs). Although drug manufacturers are required to submit postmarket AE reports to the Food and Drug Administration (FDA), this information is rarely transmitted to practitioners. In the setting of a recent FDA warning for sildenafil, the authors sought to give a better description of the AEs associated with current therapies in pediatric PH. In January 2010, a written request was made to the Food and Drug Administration for AE records of commonly used PH medications. Reports were screened for pediatric patients, analyzed in terms of AEs, and compared with the medical literature. Arbitrarily, AEs that could be attributed to concomitant medications were not attributed to the PH medication in question. Adverse events occurring in more than 5 % of events for each drug were assumed to be associated with the targeted PH medication. Between November 1997 and December 2009, 588 pediatric AE reports (death in 257 cases) were reported for the three most commonly used therapies: bosentan, epoprostenol, and sildenafil. Many of the AEs were similar to those reported previously. However, 27 AEs not previously reported in the literature (e.g., pulmonary hemorrhage, hemoptysis, and pneumonia) were found. The FDA postmarket records for PH medications in pediatric patients show a significant number of AEs. The discovery of AEs not previously reported will better inform those caring for these complex and critically ill children, and the large number of deaths suggest they may be underreported in current literature.

Memory characteristics of ring-shaped ceramic superconductors

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

Takeoka, A.; Hasunuma, M.; Sakaiya, S.

1989-03-01

For the practical application of ceramic superconductors, the authors investigated the residual magnetic field characteristics of ring-shaped ceramic superconductors in a Y-Ba-Cu-O system with high Tc. The residual magnetic field of a ring with asymmetric current paths, supplied by external currents, appeared when one of the branch currents was above the critical current. The residual magnetic field saturated when both brach currents exceeded the critical current of the ring and showed hysteresis-like characteristics. The saturated magnetic field is subject to the critical current of the ring. A superconducting ring with asymmetric current paths suggests a simple and quite new persistent-currentmore » type memory device.« less

Three Critical Tasks America's Disadvantaged Face on Their Path to College.

ERIC Educational Resources Information Center

Cabrera, Alberto F.; La Nasa, Steven M.

2000-01-01

Using data from the National Educational Longitudinal Study of 1988, examines the wide disparity of college-choice activities between socioeconomic groups. In order to highlight this disparity, analyzes three tasks that all students must complete on their path to college. (Author/EV)

Stress path dependent hydromechanical behaviour of heterogeneous carbonate rock

NASA Astrophysics Data System (ADS)

Gland, N.; Dautriat, J.; Dimanov, A.; Raphanel, J.

2010-06-01

The influence of stress paths, representative of reservoir conditions, on the hydromechanical behavior of a moderately heterogeneous carbonate has been investigated. Multiscale structural heterogeneities, common for instance in carbonate rocks, can strongly alter the mechanical response and significantly influence the evolution of flow properties with stress. Using a triaxial cell, the permeability evolutions during compression and the effects of brittle (fracture) and plastic (pore collapse) deformations at yield, were measured. A strong scattering was observed on the mechanical response both in term of compressibility and failure threshold. Using the porosity scaling predicted by an adapted effective medium theory (based on crack growth under Hertzian contact), we have rescaled the critical pressures by the normalized porosity deviation. This procedure reduces efficiently the scattering, revealing in the framework of proportional stress path loading, a linear relation between the critical pressures and the stress path parameter through all the deformation regimes. It leads to a new formulation for the critical state envelope in the 'mean stress, deviatoric stress' diagram. The attractive feature of this new yield envelope formulation relies on the fact that only the two most common different mechanical tests 'Uniaxial Compression' and 'Hydrostatic Compression', are needed to define entirely the yield envelope. Volumic strains and normalized permeabilities are finally mapped in the stresses diagram and correlated.

Finding Out Critical Points For Real-Time Path Planning

NASA Astrophysics Data System (ADS)

Chen, Wei

1989-03-01

Path planning for a mobile robot is a classic topic, but the path planning under real-time environment is a different issue. The system sources including sampling time, processing time, processes communicating time, and memory space are very limited for this type of application. This paper presents a method which abstracts the world representation from the sensory data and makes the decision as to which point will be a potentially critical point to span the world map by using incomplete knowledge about physical world and heuristic rule. Without any previous knowledge or map of the workspace, the robot will determine the world map by roving through the workspace. The computational complexity for building and searching such a map is not more than O( n2 ) The find-path problem is well-known in robotics. Given an object with an initial location and orientation, a goal location and orientation, and a set of obstacles located in space, the problem is to find a continuous path for the object from the initial position to the goal position which avoids collisions with obstacles along the way. There are a lot of methods to find a collision-free path in given environment. Techniques for solving this problem can be classified into three approaches: 1) the configuration space approach [1],[2],[3] which represents the polygonal obstacles by vertices in a graph. The idea is to determine those parts of the free space which a reference point of the moving object can occupy without colliding with any obstacles. A path is then found for the reference point through this truly free space. Dealing with rotations turns out to be a major difficulty with the approach, requiring complex geometric algorithms which are computationally expensive. 2) the direct representation of the free space using basic shape primitives such as convex polygons [4] and overlapping generalized cones [5]. 3) the combination of technique 1 and 2 [6] by which the space is divided into the primary convex region, overlap region and obstacle region, then obstacle boundaries with attribute values are represented by the vertices of the hypergraph. The primary convex region and overlap region are represented by hyperedges, the centroids of overlap form the critical points. The difficulty is generating segment graph and estimating of minimum path width. The all techniques mentioned above need previous knowledge about the world to make path planning and the computational cost is not low. They are not available in an unknow and uncertain environment. Due to limited system resources such as CPU time, memory size and knowledge about the special application in an intelligent system (such as mobile robot), it is necessary to use algorithms that provide the good decision which is feasible with the available resources in real time rather than the best answer that could be achieved in unlimited time with unlimited resources. A real-time path planner should meet following requirements: - Quickly abstract the representation of the world from the sensory data without any previous knowledge about the robot environment. - Easily update the world model to spell out the global-path map and to reflect changes in the robot environment. - Must make a decision of where the robot must go and which direction the range sensor should point to in real time with limited resources. The method presented here assumes that the data from range sensors has been processed by signal process unite. The path planner will guide the scan of range sensor, find critical points, make decision where the robot should go and which point is poten- tial critical point, generate the path map and monitor the robot moves to the given point. The program runs recursively until the goal is reached or the whole workspace is roved through.

Non-gynecologic cytology on liquid-based preparations: A morphologic review of facts and artifacts.

PubMed

Hoda, Rana S

2007-10-01

Liquid-based preparations (LBP) are increasingly being used both for gynecologic (gyn) and non-gynecologic (non-gyn) cytology including fine needle aspirations (FNA). The two FDA-approved LBP currently in use include ThinPrep (TP), (Cytyc Corp, Marlborough, MA) and SurePath (SP), (TriPath Imaging Inc., Burlington, NC). TP was approved for cervico-vaginal (Pap test) cytology in 1996 and SP in 1999 and both have since also been used for non-gyn cytology. In the LBP, instead of being smeared, cells are rinsed into a liquid preservative collection medium and processed on automated devices. Even after a decade of use, the morphological interpretation of LBP remains a diagnostic challenge because of somewhat altered morphology and artifacts or facts resulting from the fixation and processing techniques. These changes include cleaner background with altered or reduced background and extracellular elements; architectural changes such as smaller cell clusters and sheets, breakage of papillae; altered cell distribution with more dyscohesion and changes in cellular morphology with enhanced nuclear features, smaller cell size and slightly more three-dimensional (3-D) clusters. Herein, we review the published literature on morphological aspects of LBP for non-gyn cytology. (c) 2007 Wiley-Liss, Inc.

Reply to "Comment on `Particle path through a nested Mach-Zehnder interferometer' "

NASA Astrophysics Data System (ADS)

Griffiths, Robert B.

2017-06-01

The correctness of the consistent histories analysis of weakly interacting probes, related to the path of a particle, is maintained against the criticisms in the Comment, and against the alternative approach described there, which receives no support from standard (textbook) quantum mechanics.

Sociological Theory and Youth Aspiration Research: A Critical Overview.

ERIC Educational Resources Information Center

Picou, J. Steven; Wells, Richard H.

Reviewing sociological theories relative to youth aspiration research, the following thesis was presented: "pre-path analysis aspiration research was characterized by a person-centered, middle-range functionalist approach which eventually shifted to a person-centered, functionalist-system approach with the introduction of the path model…

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

FDA Kids' Home Page

MedlinePlus

... and Drug Administration A to Z Index Follow FDA En Español Search FDA Submit search Popular Content Home Food Drugs Medical ... 日本語 | فارسی | English FDA Accessibility Careers FDA Basics FOIA No FEAR Act ...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

78 FR 18233 - Medical Devices; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... the right column: Section Remove Add 814.20 http://www.fda.gov/ http://www.fda.gov/ cdrh/devadvice.../ PremarketApproval PMA/default.htm. 822.7 http://www.fda.gov/ http://www.fda.gov/ cdrh/ombudsman/ AboutFDA/ dispute.html. CentersOffices/ OfficeofMedicalPr oductsandTobacco/ CDRH/ CDRHOmbudsman/ default.htm. 822.15...

Case histories in pharmaceutical risk management.

PubMed

McCormick, Cynthia G; Henningfield, Jack E; Haddox, J David; Varughese, Sajan; Lindholm, Anders; Rosen, Susan; Wissel, Janne; Waxman, Deborah; Carter, Lawrence P; Seeger, Vickie; Johnson, Rolley E

2009-12-01

The development and implementation of programs in the U.S. to minimize risks and assess unintended consequences of new medications has been increasingly required by the Food and Drug Administration (FDA) since the mid 1990s. This paper provides four case histories of risk management and post-marketing surveillance programs utilized recently to address problems associated with possible abuse, dependence and diversion. The pharmaceutical sponsors of each of these drugs were invited to present their programs and followed a similar template for their summaries that are included in this article. The drugs and presenting companies were OxyContin, an analgesic marketed by Purdue Pharma L.P., Daytrana and Vyvanse, ADHD medications marketed by Shire Pharmaceuticals, Xyrem for narcolepsy marketed by Jazz Pharmaceuticals, and Subutex and Suboxone for opioid dependence marketed by Reckitt Benckiser Pharmaceuticals Inc. These case histories and subsequent discussions provide invaluable real-world examples and illustrate both the promise of risk management programs in providing a path to market and/or for keeping on the market drugs with serious potential risks. They also illustrate the limitations of such programs in actually controlling unintended consequences, as well as the challenge of finding the right balance of reducing risks without posing undue barriers to patient access. These experiences are highly relevant as the FDA increasingly requires pharmaceutical sponsors to develop and implement the more formalized and enforceable versions of the risk management term Risk Evaluation and Mitigation Strategies (REMS).

21 CFR 1.280 - How must you submit prior notice?

Code of Federal Regulations, 2010 CFR

2010-04-01

... to FDA. You must submit all prior notice information in the English language, except that an... Commercial System (ABI/ACS); or (2) The FDA PNSI at http://www.access.fda.gov. You must submit prior notice through the FDA Prior Notice System Interface (FDA PNSI) for articles of food imported or offered for...

78 FR 65329 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... Safety Testing of Sunlamp Products'' Form FDA 3632 ``Guide for Preparing Product Reports on Lasers and Products Containing Lasers'' Form FDA 3633''General Variance Request'' Form FDA 3634 ``Television Products Annual Report'' Form FDA 3635 ``Laser Light Show Notification'' Form FDA 3636 ``Guide for Preparing...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-12

... Lasers and Products Containing Lasers'' FDA Form 3633 ``General Variance Request'' FDA Form 3634 ``Television Products Annual Report'' FDA Form 3635 ``Laser Light Show Notification'' FDA Form 3636 ``Guide for Preparing Annual Reports on Radiation Safety Testing of Laser and Laser Light Show Products'' FDA Form 3637...

75 FR 26964 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-13

... of Sunlamps and Sunlamp Products'' FDA Form 3632 ``Guide for Preparing Product Reports on Lasers and Products Containing Lasers'' FDA Form 3633 ``General Variance Request'' FDA Form 3634 ``Television Products Annual Report'' FDA Form 3635 ``Laser Light Show Notification'' FDA Form 3636 ``Guide for Preparing...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2012 CFR

2012-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2013 CFR

2013-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 2 2014-10-01 2014-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2010 CFR

2010-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2011 CFR

2011-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2014 CFR

2014-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 2 2012-10-01 2012-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

76 FR 30175 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1999-D-0792] (Formerly FDA-1999-D-0792) Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial.... SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance...

21 CFR 830.100 - FDA accreditation of an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA accreditation of an issuing agency. 830.100... (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA Accreditation of an Issuing Agency § 830.100 FDA... issuing agency. (b) Accreditation criteria. FDA may accredit an organization as an issuing agency, if the...

Search Path Mapping: A Versatile Approach for Visualizing Problem-Solving Behavior.

ERIC Educational Resources Information Center

Stevens, Ronald H.

1991-01-01

Computer-based problem-solving examinations in immunology generate graphic representations of students' search paths, allowing evaluation of how organized and focused their knowledge is, how well their organization relates to critical concepts in immunology, where major misconceptions exist, and whether proper knowledge links exist between content…

Atropa belladonna neurotoxicity: Implications to neurological disorders.

PubMed

Kwakye, Gunnar F; Jiménez, Jennifer; Jiménez, Jessica A; Aschner, Michael

2018-06-01

Atropa belladonna, commonly known as belladonna or deadly nightshade, ranks among one of the most poisonous plants in Europe and other parts of the world. The plant contains tropane alkaloids including atropine, scopolamine, and hyoscyamine, which are used as anticholinergics in Food and Drug Administration (FDA) approved drugs and homeopathic remedies. These alkaloids can be very toxic at high dose. The FDA has recently reported that Hyland's baby teething tablets contain inconsistent amounts of Atropa belladonna that may have adverse effects on the nervous system and cause death in children, thus recalled the product in 2017. A greater understanding of the neurotoxicity of Atropa belladonna and its modification of genetic polymorphisms in the nervous system is critical in order to develop better treatment strategies, therapies, regulations, education of at-risk populations, and a more cohesive paradigm for future research. This review offers an integrated view of the homeopathy and neurotoxicity of Atropa belladonna in children, adults, and animal models as well as its implications to neurological disorders. Particular attention is dedicated to the pharmaco/toxicodynamics, pharmaco/toxicokinetics, pathophysiology, epidemiological cases, and animal studies associated with the effects of Atropa belladonna on the nervous system. Additionally, we discuss the influence of active tropane alkaloids in Atropa belladonna and other similar plants on FDA-approved therapeutic drugs for treatment of neurological disorders. Copyright © 2018. Published by Elsevier Ltd.

Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection

PubMed Central

Tummers, Willemieke S.; Warram, Jason M.; Tipirneni, Kiranya E.; Fengler, John; Jacobs, Paula; Shankar, Lalitha; Henderson, Lori; Ballard, Betsy; Pogue, Brian W.; Weichert, Jamey P.; Bouvet, Michael; Sorger, Jonathan; Contag, Christopher H.; Frangioni, John V.; Tweedle, Michael F.; Basilion, James P.; Gambhir, Sanjiv S.; Rosenthal, Eben L.

2017-01-01

Considerable advances in cancer-specific optical imaging have improved the precision of tumor resection. In comparison to traditional imaging modalities, this technology is unique in its ability to provide real-time feedback to the operating surgeon. Given the significant clinical implications of optical imaging, there is an urgent need to standardize surgical navigation tools and contrast agents to facilitate swift regulatory approval. Because fluorescence-enhanced surgery requires a combination of both device and drug, each may be developed in conjunction, or separately, which are important considerations in the approval process. This report is the result of a one-day meeting held on May 4, 2016 with officials from the National Cancer Institute, the FDA, members of the American Society of Image-Guided Surgery, and members of the World Molecular Imaging Society, which discussed consensus methods for FDA-directed human testing and approval of investigational optical imaging devices as well as contrast agents for surgical applications. The goal of this workshop was to discuss FDA approval requirements and the expectations for approval of these novel drugs and devices, packaged separately or in combination, within the context of optical surgical navigation. In addition, the workshop acted to provide clarity to the research community on data collection and trial design. Reported here are the specific discussion items and recommendations from this critical and timely meeting. PMID:28428283

Jovan Skerlic as a Life Tutor

ERIC Educational Resources Information Center

Mumovic, Ana

2015-01-01

The paper studies and illuminates Jovan Skerlic's social function and "criticism anatomy" in his "History of Serbian Literature." The object of analysis is the act and actors of Skerlic's engaged criticism and method relying on facts. It is the path taken a hundred years later by Serbian criticism and literature as culture and…

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

77 FR 52036 - Privacy Act of 1974; Report of a New System of Records; FDA Records Related to Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0253] Privacy Act of 1974; Report of a New System of Records; FDA Records Related to Research Misconduct... Drug Administration's (FDA's) regulations for the protection of privacy, FDA is publishing notice of a...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 830.220 - Termination of FDA service as an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Termination of FDA service as an issuing agency... SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA as an Issuing Agency § 830.220 Termination of FDA service as an issuing agency. (a) FDA may end our services as an issuing agency if we...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

FDA Warns About Stem Cell Therapies

MedlinePlus

... For Consumers Consumer Updates FDA Warns About Stem Cell Therapies Share Tweet Linkedin Pin it More sharing ... the boxed section below for more advice. Stem Cell Uses and FDA Regulation The FDA has the ...

Cooperative path planning for multi-USV based on improved artificial bee colony algorithm

NASA Astrophysics Data System (ADS)

Cao, Lu; Chen, Qiwei

2018-03-01

Due to the complex constraints, more uncertain factors and critical real-time demand of path planning for multiple unmanned surface vehicle (multi-USV), an improved artificial bee colony (I-ABC) algorithm were proposed to solve the model of cooperative path planning for multi-USV. First the Voronoi diagram of battle field space is conceived to generate the optimal area of USVs paths. Then the chaotic searching algorithm is used to initialize the collection of paths, which is regard as foods of the ABC algorithm. With the limited data, the initial collection can search the optimal area of paths perfectly. Finally simulations of the multi-USV path planning under various threats have been carried out. Simulation results verify that the I-ABC algorithm can improve the diversity of nectar source and the convergence rate of algorithm. It can increase the adaptability of dynamic battlefield and unexpected threats for USV.

Environmental Impact Analysis Process. Environmental Assessment for Defense Satellite Communications System III With Integrated Apogee Boost System

DTIC Science & Technology

1995-07-01

spectabilis Royal fern C FDA n/o Remirea maritima Beach star E FDA, FNAI o Scaevola plumeria Scaevola T FDA o Tillandsia simulata Wildpine; air plant...unnamed) T FDA n/o Tillandsia utriculata Giant wildpine; giant air plant C FDA o 1 E = Endangered; T = Threatened; T(S/A) = Threatened due to

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare Department... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

21 CFR 830.210 - Eligibility for use of FDA as an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Eligibility for use of FDA as an issuing agency... SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA as an Issuing Agency § 830.210 Eligibility for use of FDA as an issuing agency. When FDA acts as an issuing agency, any labeler will be...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

Non-Ionizing Radiation Used in Microwave Ovens

MedlinePlus

... Human Services (HHS), U.S. Food and Drug Administration (FDA) FDA's Center for Devices and Radiological Health (CDRH) sets ... public health. These standards can be viewed on FDA's Code of Federal Regulations on Microwave Ovens . FDA ...

A Novel Dual Separate Paths (DSP) Algorithm Providing Fault-Tolerant Communication for Wireless Sensor Networks.

PubMed

Tien, Nguyen Xuan; Kim, Semog; Rhee, Jong Myung; Park, Sang Yoon

2017-07-25

Fault tolerance has long been a major concern for sensor communications in fault-tolerant cyber physical systems (CPSs). Network failure problems often occur in wireless sensor networks (WSNs) due to various factors such as the insufficient power of sensor nodes, the dislocation of sensor nodes, the unstable state of wireless links, and unpredictable environmental interference. Fault tolerance is thus one of the key requirements for data communications in WSN applications. This paper proposes a novel path redundancy-based algorithm, called dual separate paths (DSP), that provides fault-tolerant communication with the improvement of the network traffic performance for WSN applications, such as fault-tolerant CPSs. The proposed DSP algorithm establishes two separate paths between a source and a destination in a network based on the network topology information. These paths are node-disjoint paths and have optimal path distances. Unicast frames are delivered from the source to the destination in the network through the dual paths, providing fault-tolerant communication and reducing redundant unicast traffic for the network. The DSP algorithm can be applied to wired and wireless networks, such as WSNs, to provide seamless fault-tolerant communication for mission-critical and life-critical applications such as fault-tolerant CPSs. The analyzed and simulated results show that the DSP-based approach not only provides fault-tolerant communication, but also improves network traffic performance. For the case study in this paper, when the DSP algorithm was applied to high-availability seamless redundancy (HSR) networks, the proposed DSP-based approach reduced the network traffic by 80% to 88% compared with the standard HSR protocol, thus improving network traffic performance.

The selling of olestra.

PubMed Central

Nestle, M

1998-01-01

The Procter & Gamble Company spent 30 years and an estimated $500 million to bring its non-digestible fat substitute, olestra, to market. The Food and Drug Administration approved olestra as a food additive but requires products containing olestra to carry a warning statement about its potential effects on gastrointestinal function. In obtaining approval for olestra, P&G conducted a lengthy, persistent, and comprehensive campaign to enlist support from members of Congress; FDA staff; and food, nutrition, and health professionals. This campaign raises larger questions about corporate influence on government policies, and the relationships of corporations to health professionals. To address these larger concerns, the author reviews the history of olestra's approval; describes P&G's campaign to obtain support from FDA and Congress, to defend olestra against critics, and to market it to professionals, the press, and consumers; and suggests implications for public health policies. Images p508-a p509-a p510-a p511-a p512-a p513-a p515-a p516-a p517-a PMID:9847922

OpenFDA: an innovative platform providing access to a wealth of FDA's publicly available data.

PubMed

Kass-Hout, Taha A; Xu, Zhiheng; Mohebbi, Matthew; Nelsen, Hans; Baker, Adam; Levine, Jonathan; Johanson, Elaine; Bright, Roselie A

2016-05-01

The objective of openFDA is to facilitate access and use of big important Food and Drug Administration public datasets by developers, researchers, and the public through harmonization of data across disparate FDA datasets provided via application programming interfaces (APIs). Using cutting-edge technologies deployed on FDA's new public cloud computing infrastructure, openFDA provides open data for easier, faster (over 300 requests per second per process), and better access to FDA datasets; open source code and documentation shared on GitHub for open community contributions of examples, apps and ideas; and infrastructure that can be adopted for other public health big data challenges. Since its launch on June 2, 2014, openFDA has developed four APIs for drug and device adverse events, recall information for all FDA-regulated products, and drug labeling. There have been more than 20 million API calls (more than half from outside the United States), 6000 registered users, 20,000 connected Internet Protocol addresses, and dozens of new software (mobile or web) apps developed. A case study demonstrates a use of openFDA data to understand an apparent association of a drug with an adverse event. With easier and faster access to these datasets, consumers worldwide can learn more about FDA-regulated products. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved.

Novel Osteoinductive Photo-cross-linkable Chitosan-lactide-fibrinogen Hydrogels Enhance Bone Regeneration in Critical Size Segmental Bone Defects

DTIC Science & Technology

2014-08-01

an absorbable collagen sponge (ACS) is the FDA-approved device for clinical applications including lumbar spine fusion, open tibial fractures, and...fibrinogen on the morphological change of the CL hydrogels was observed. The hydrogel samples were incubated into PBS (pH 7.4) at 37°C for 1 day and... morphology was observed qualitatively using a Zeiss Axiovert 200 microscope (Carl Zeiss Microimaging, Thornwood, NY). Photomicrographs of cells

Studies of the Effects of Perfluorocarbon Emulsions on Platelet Number and Function in Models of Critical Battlefield Injury

DTIC Science & Technology

2016-09-01

to treat traumatic injuries by enhanced delivery of oxygen . A concerned side effect of PFC may cause thrombocytopenia (TCYP). FDA requests...Morris, A., Zhu, J., Spiess, B.D., Parsons, J.T. The Effect of Perfluorocarbon Oxygen Therapeutics in a Sheep Survival Model of Severe Hemorrhagic...of effectively oxygenating sensitive tissue in the absence of adequate hemoglobin and/or blood flow. PFC emulsion volumes required for efficacy can

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2013 CFR

2013-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

FDA Issues Final Guidance Clarifying FDA and EPA Jurisdiction over Mosquito-Related Products

EPA Pesticide Factsheets

FDA finalized guidance to provide information on FDA and EPA jurisdiction over the regulation of mosquito-related products intended to function as pesticides, including those products intended to function as pesticides

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2011 CFR

2011-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2010 CFR

2010-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2012 CFR

2012-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

Benefit from NASA

NASA Image and Video Library

1997-01-01

When NASA started plarning for manned space travel in 1959, the myriad challenges of sustaining life in space included a seemingly mundane but vitally important problem: How and what do you feed an astronaut? There were two main concerns: preventing food crumbs from contaminating the spacecraft's atmosphere or floating into sensitive instruments, and ensuring complete freedom from potentially catastrophic disease-producing bacteria, viruses, and toxins. To solve these concerns, NASA enlisted the help of the Pillsbury Company. Pillsbury quickly solved the first problem by coating bite-size foods to prevent crumbling. They developed the hazard analysis and critical control point (HACCP) concept to ensure against bacterial contamination. Hazard analysis is a systematic study of product, its ingredients, processing conditions, handling, storage, packing, distribution, and directions for consumer use to identify sensitive areas that might prove hazardous. Hazard analysis provides a basis for blueprinting the Critical Control Points (CCPs) to be monitored. CCPs are points in the chain from raw materials to the finished product where loss of control could result in unacceptable food safety risks. In early 1970, Pillsbury plants were following HACCP in production of food for Earthbound consumers. Pillsbury's subsequent training courses for Food and Drug Administration (FDA) personnel led to the incorporation of HACCP in the FDA's Low Acid Canned Foods Regulations, set down in the mid-1970s to ensure the safety of all canned food products in the U.S.

Food Processing Control

NASA Technical Reports Server (NTRS)

1997-01-01

When NASA started plarning for manned space travel in 1959, the myriad challenges of sustaining life in space included a seemingly mundane but vitally important problem: How and what do you feed an astronaut? There were two main concerns: preventing food crumbs from contaminating the spacecraft's atmosphere or floating into sensitive instruments, and ensuring complete freedom from potentially catastrophic disease-producing bacteria, viruses, and toxins. To solve these concerns, NASA enlisted the help of the Pillsbury Company. Pillsbury quickly solved the first problem by coating bite-size foods to prevent crumbling. They developed the hazard analysis and critical control point (HACCP) concept to ensure against bacterial contamination. Hazard analysis is a systematic study of product, its ingredients, processing conditions, handling, storage, packing, distribution, and directions for consumer use to identify sensitive areas that might prove hazardous. Hazard analysis provides a basis for blueprinting the Critical Control Points (CCPs) to be monitored. CCPs are points in the chain from raw materials to the finished product where loss of control could result in unacceptable food safety risks. In early 1970, Pillsbury plants were following HACCP in production of food for Earthbound consumers. Pillsbury's subsequent training courses for Food and Drug Administration (FDA) personnel led to the incorporation of HACCP in the FDA's Low Acid Canned Foods Regulations, set down in the mid-1970s to ensure the safety of all canned food products in the U.S.

Time-Critical Cooperative Path Following of Multiple Unmanned Aerial Vehicles over Time-Varying Networks

DTIC Science & Technology

2013-03-01

Ciência e a Tecnologia . References [1] Kaminer, I., Pascoal, A.M., Hallberg, E., and Silvestreo, C., “Trajectory Tracking for Autonomous Vehicles: An...for publication). [53] Cichella, V., Xargay, E., Dobrokhodov, V., Kaminer, I., Pascoal, A. M., and Hovakimyan, N., “Geometric 3D Path-Following

Education through Movies: Improving Teaching Skills and Fostering Reflection among Students and Teachers

ERIC Educational Resources Information Center

Blasco, Pablo Gonzalez; Moreto, Graziela; Blasco, Mariluz González; Levites, Marcelo Rozenfeld; Janaudis, Marco Aurelio

2015-01-01

Learning through aesthetics--in which cinema is included--stimulates learner reflection. As emotions play key roles in learning attitudes and changing behavior, teachers must impact learners affective domain. Since feelings exist before concepts, the affective path is a critical path to the rational process of learning. Cinema is the audiovisual…

Wells Fargo Innovation Incubator (IN²) | NREL

Science.gov Websites

Incubator (IN2) is now a $30 million program supporting innovative technologies and innovators. IN2 is buildings portfolio of Wells Fargo to help companies derisk technologies and ease their path to market companies' technologies to help them meet critical validation milestones on the path to market. Companies

Disfluencies along the Garden Path: Brain Electrophysiological Evidence of Disrupted Sentence Processing

ERIC Educational Resources Information Center

Maxfield, Nathan D.; Lyon, Justine M.; Silliman, Elaine R.

2009-01-01

Bailey and Ferreira (2003) hypothesized and reported behavioral evidence that disfluencies (filled and silent pauses) undesirably affect sentence processing when they appear before disambiguating verbs in Garden Path (GP) sentences. Disfluencies here cause the parser to "linger" on, and apparently accept as correct, an erroneous parse. Critically,…

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

Patient Experience Data in US Food and Drug Administration (FDA) Regulatory Decision Making:: A Policy Process Perspective.

PubMed

Kuehn, Carrie M

2018-01-01

The influence of patient advocates on FDA regulatory decision making has increased. Despite enhanced engagement with FDA, there remain challenges to achieving the regulatory goals of patients within FDA's regulatory framework. Gaps exist between patient advocates' knowledge of the agency's processes and FDA's need for rigorous, clinically meaningful patient experience data. This study examined the policy process in which patient experience data are collected by patient advocates and provided to FDA for regulatory decision making. Semistructured, narrative interviews were conducted with 14 professionals working in patient advocacy or at FDA. The purpose was to examine, in depth, participants' perceptions and experiences regarding this new regulatory process. Interviews were coded and examined for themes. The use of patient experience data by FDA is an evolving regulatory process. Participants identified a number of barriers and contributors to regulatory success. Well-organized and sophisticated patient advocacy groups with access to scientific and policy expertise are more likely to find success meeting FDA's patient experience data requirements. A conceptual model of this regulatory process was developed. Use of patient experience data by FDA has the potential to positively influence the regulation of medical products in the United States. Success within this new regulatory process will depend on clear guidance from FDA regarding the collection, analysis, and use of patient experience data. Patient advocacy groups must enhance internal capacity and expertise while engaging in substantive collaborations with FDA and other stakeholders in order to meaningfully contribute to the regulatory review of new therapeutics.

Integrating Critical Thinking Instruction and Assessment into Online University Courses: An Action Research Study

ERIC Educational Resources Information Center

Mason Heinrichs, Kim R.

2016-01-01

Universities claim that improved critical thinking ability is an educational outcome for their graduates, but they seldom create a path for students to achieve that outcome. In this practitioner action research study, the author created a job aid, entitled "Critical Thinking as a Differentiator for Distinguished Performance," to help…

Fluorescein Diacetate Microplate Assay in Cell Viability Detection.

PubMed

Chen, Xi; Yang, Xiu-Ying; Fang, Lian-Hua; DU, Guan-Hua

2016-12-20

Objective To investigate the application of the fluorescein diacetate (FDA) microplate assay in cell viability detection. Methods Cells were seeded in a 96-well culture plate until detection. After incubated with FDA,the plate was detected by fluorescence microplate analyzer. The effects of FDA incubation duration,concentration,and other factors on the assay's accuracy and stability were assessed. We also compared the results of FDA with methyl thiazolyl(MTT) in terms of cell numbers and H 2 O 2 injury. Results Within 0-30 minutes,the fluorescence-cell number coefficient of FDA assay increased with duration and reached 0.99 in 27-30 minutes. The optimum concentration of final FDA in this study was 10-30 μg/ml. On cell viability detection,the result of FDA method was equivalent to MTT method. As to H 2 O 2 injury assay,the sensitivity of FDA method was superior to MTT on the higher concentration H 2 O 2 treatment due to a relative shorter duration for detection. Conclusion As a stable and reliable method,FDA is feasible for cell variability detection under varied conditions.

76 FR 1180 - FDA Transparency Initiative: Improving Transparency to Regulated Industry

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

...] FDA Transparency Initiative: Improving Transparency to Regulated Industry AGENCY: Food and Drug... the Transparency Initiative, the Food and Drug Administration (FDA) is announcing the availability of a report entitled ``FDA Transparency Initiative: Improving Transparency to Regulated Industry.'' The...

77 FR 70955 - FDA Actions Related to Nicotine Replacement Therapies and Smoking-Cessation Products; Report to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-28

.... FDA-2012-N-1148] FDA Actions Related to Nicotine Replacement Therapies and Smoking-Cessation Products... comments. SUMMARY: The Food and Drug Administration (FDA) is announcing a 1-day public hearing to obtain...

Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

DTIC Science & Technology

2016-10-01

consensus meeting, with input from investigators in the Prostate Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study...Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study Endpoint and Label Development Team, and FDA Division of...Abstract. American Society of Clinical Oncology . Chicago IL, June 1-5, 2013. INVENTIONS, PATENTS AND LICENSES None 11 REPORTABLE OUTCOMES

Implementation Of Fuzzy Approach To Improve Time Estimation [Case Study Of A Thermal Power Plant Is Considered

NASA Astrophysics Data System (ADS)

Pradhan, Moumita; Pradhan, Dinesh; Bandyopadhyay, G.

2010-10-01

Fuzzy System has demonstrated their ability to solve different kinds of problem in various application domains. There is an increasing interest to apply fuzzy concept to improve tasks of any system. Here case study of a thermal power plant is considered. Existing time estimation represents time to complete tasks. Applying fuzzy linear approach it becomes clear that after each confidence level least time is taken to complete tasks. As time schedule is less than less amount of cost is needed. Objective of this paper is to show how one system becomes more efficient in applying Fuzzy Linear approach. In this paper we want to optimize the time estimation to perform all tasks in appropriate time schedules. For the case study, optimistic time (to), pessimistic time (tp), most likely time(tm) is considered as data collected from thermal power plant. These time estimates help to calculate expected time(te) which represents time to complete particular task to considering all happenings. Using project evaluation and review technique (PERT) and critical path method (CPM) concept critical path duration (CPD) of this project is calculated. This tells that the probability of fifty percent of the total tasks can be completed in fifty days. Using critical path duration and standard deviation of the critical path, total completion of project can be completed easily after applying normal distribution. Using trapezoidal rule from four time estimates (to, tm, tp, te), we can calculate defuzzyfied value of time estimates. For range of fuzzy, we consider four confidence interval level say 0.4, 0.6, 0.8,1. From our study, it is seen that time estimates at confidence level between 0.4 and 0.8 gives the better result compared to other confidence levels.

Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study.

PubMed

Maréchaux, Sylvestre; Rusinaru, Dan; Jobic, Yannick; Ederhy, Stéphane; Donal, Erwan; Réant, Patricia; Arnalsteen, Elise; Boulanger, Jacques; Garban, Thierry; Ennezat, Pierre-Vladimir; Jeu, Antoine; Szymanski, Catherine; Tribouilloy, Christophe

2015-02-01

The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation ≥ mild and/or mitral regurgitation ≥ moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD. This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P ≤ 0.001). FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

Investigation of the interfacial reaction between metal and fluorine-contained polyimides

NASA Astrophysics Data System (ADS)

Yang, Ching-Yu; Chen, J. S.; Hsu, S. L. C.

2005-07-01

In this work, thin metal films (Cr and Ta) were deposited on fluorine-contained polyimides, 6FDA-BisAAF, and 6FDA-PPD. The chemical states of the metal/polyimide samples were characterized by using x-ray photoelectron spectroscopy (XPS). XPS analysis reveals that metal-C, C-O, and metal-O bondings are present in metallized 6FDA-BisAAF and 6FDA-PPD. C-F bonds are observed in bare 6FDA-BisAAF and 6FDA-PPD however, they are not seen in the metallized samples. Disappearance of the C-F bonding is attributed to the disruption of CF3 side groups from the main chains of 6FDA-BisAAF and 6FDA-PPD when the chains are exposed to the plasma during the metal deposition. Nevertheless, the disruption of CF3 side groups also creates sites for the formation of metal-C or C-O bondings, which provide a positive adhesion strength at the metal/polyimide interface, as revealed by the tape test.

Reflections on the US FDA's Warning on Direct-to-Consumer Genetic Testing.

PubMed

Yim, Seon-Hee; Chung, Yeun-Jun

2014-12-01

In November 2013, the US Food and Drug Administration (FDA) sent a warning letter to 23andMe, Inc. and ordered the company to discontinue marketing of the 23andMe Personal Genome Service (PGS) until it receives FDA marketing authorization for the device. The FDA considers the PGS as an unclassified medical device, which requires premarket approval or de novo classification. Opponents of the FDA's action expressed their concerns, saying that the FDA is overcautious and paternalistic, which violates consumers' rights and might stifle the consumer genomics field itself, and insisted that the agency should not restrict direct-to-consumer (DTC) genomic testing without empirical evidence of harm. Proponents support the agency's action as protection of consumers from potentially invalid and almost useless information. This action was also significant, since it reflected the FDA's attitude towards medical application of next-generation sequencing techniques. In this review, we followed up on the FDA-23andMe incident and evaluated the problems and prospects for DTC genetic testing.

The history and contemporary challenges of the US Food and Drug Administration.

PubMed

Borchers, Andrea T; Hagie, Frank; Keen, Carl L; Gershwin, M Eric

2007-01-01

The year 2006 marks the 100th anniversary of the regulatory agency now known as the US Food and Drug Administration (FDA), the first consumer protection agency of the federal government and arguably the most influential regulatory agency in the world. The FDA thus plays an integral role in the use of pharmaceuticals, not only in the United States but worldwide. The goal of this review was to present an overview of the FDA and place its current role in the perspectives of history and contemporary needs. Relevant materials for this review were identified through a search of the English-language literature indexed on MEDLINE (through 2006) using the main search terms United States Food and Drug Administration, FDA, history of the FDA, drug approvals, drug legislation, and FDA legislation. Results from the initial searches were then explored further. The statute that created the bureau which later became the FDA established this agency to prohibit interstate commerce of adulterated foods, drinks, and drugs. The Food, Drug, and Cosmetic Act that replaced it in 1938, and subsequent food and drug laws and amendments, expanded the FDA's responsibilities to cosmetics, medical devices, biological products, and radiation-emitting products. These amendments have also established the FDA as a mainly preventive regulatory agency that relies chiefly on pre-market control. As such, the FDA has played an important role in shaping the modern pharmaceutical industry by making the scientific approach and the clinical trial process the standard for establishing safety and efficacy and by making rigorous scientific analysis the predominant component of the process for pharmaceutical regulation. As shown in this review, the evolution of the FDA can be described as a series of "crisis-legislation-adaptation" cycles: a public health crisis promoted the passage of congressional legislation, which was then followed by implementation of the law by the FDA. However, the crises the FDA faces currently are likely to be overcome only under strong and permanent leadership willing to redefine the role and procedures of the FDA with an open mind.

Current FDA directives for promoting public health

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

Hayes, A.H. Jr.

1982-03-01

The current directions of the FDA are outlined. The underlying philosophy of the FDA under the Reagan Administration is that both the private sector and the government must address the responsibilities to which they are best suited for the health-care system to work more efficiently. To facilitate this, FDA is conducting comprehensive reviews of FDA regulations and the drug-evaluation process. There are many dimensions to promoting public health, and the FDA alone cannot assure an adequate supply of safe and effective drugs. Innovative science and technology are needed to develop new drugs, followed by maximum potentiation (maximum good and leastmore » harm) after FDA approval. Hospital pharmacists have a role in maximizing the potential benefits of drugs through pharmacy and therapeutics committees. The current status of the pilot program for patient package inserts is described. The response at a recent hearing on the program indicates that the responsibility to protect the public health is shared by the government, health professions, industry, and the public. The FDA's campaign on sodium is based on that shared responsibility. By improving communication and building upon their common objections, both pharmacy and the FDA can do their jobs successfully.« less

OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications.

PubMed

Böhm, Ruwen; von Hehn, Leocadie; Herdegen, Thomas; Klein, Hans-Joachim; Bruhn, Oliver; Petri, Holger; Höcker, Jan

2016-01-01

Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics. To address these issues, we have developed OpenVigil FDA, a novel web-based pharmacovigilance analysis tool which uses the openFDA online interface of the Food and Drug Administration (FDA) to access U.S. American and international pharmacovigilance data from the Adverse Event Reporting System (AERS). OpenVigil FDA provides disproportionality analyses to (i) identify the drug most likely evoking a new adverse event, (ii) compare two drugs concerning their safety profile, (iii) check arbitrary combinations of two drugs for unknown drug-drug interactions and (iv) enhance the relevance of results by identifying confounding factors and eliminating them using background correction. We present examples for these applications and discuss the promises and limits of pharmacovigilance, openFDA and OpenVigil FDA. OpenVigil FDA is the first public available tool to apply pharmacovigilance findings directly to real-life clinical problems. OpenVigil FDA does not require special licenses or statistical programs.

76 FR 38184 - Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Recall...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0439] Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Recall Regulations AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA...

Software-based data path for raster-scanned multi-beam mask lithography

NASA Astrophysics Data System (ADS)

Rajagopalan, Archana; Agarwal, Ankita; Buck, Peter; Geller, Paul; Hamaker, H. Christopher; Rao, Nagswara

2016-10-01

According to the 2013 SEMATECH Mask Industry Survey,i roughly half of all photomasks are produced using laser mask pattern generator ("LMPG") lithography. LMPG lithography can be used for all layers at mature technology nodes, and for many non-critical and semi-critical masks at advanced nodes. The extensive use of multi-patterning at the 14-nm node significantly increases the number of critical mask layers, and the transition in wafer lithography from positive tone resist to negative tone resist at the 14-nm design node enables the switch from advanced binary masks back to attenuated phase shifting masks that require second level writes to remove unwanted chrome. LMPG lithography is typically used for second level writes due to its high productivity, absence of charging effects, and versatile non-actinic alignment capability. As multi-patterning use expands from double to triple patterning and beyond, the number of LMPG second level writes increases correspondingly. The desire to reserve the limited capacity of advanced electron beam writers for use when essential is another factor driving the demand for LMPG capacity. The increasing demand for cost-effective productivity has kept most of the laser mask writers ever manufactured running in production, sometimes long past their projected lifespan, and new writers continue to be built based on hardware developed some years ago.ii The data path is a case in point. While state-ofthe- art when first introduced, hardware-based data path systems are difficult to modify or add new features to meet the changing requirements of the market. As data volumes increase, design styles change, and new uses are found for laser writers, it is useful to consider a replacement for this critical subsystem. The availability of low-cost, high-performance, distributed computer systems combined with highly scalable EDA software lends itself well to creating an advanced data path system. EDA software, in routine production today, scales well to hundreds or even thousands of CPU-cores, offering the potential for virtually unlimited capacity. Features available in EDA software such as sizing, scaling, tone reversal, OPC, MPC, rasterization, and others are easily adapted to the requirements of a data path system. This paper presents the motivation, requirements, design and performance of an advanced, scalable software data path system suitable to support multi-beam laser mask lithography.

Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis.

PubMed

Wang, Bo; Franklin, Jessica M; Eddings, Wesley; Landon, Joan; Kesselheim, Aaron S

2016-01-01

Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved ("off-label") uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children. Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone. During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79). The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

Codification of scan path parameters and development of perimeter scan strategies for 3D bowl-shaped laser forming

NASA Astrophysics Data System (ADS)

Tavakoli, A.; Naeini, H. Moslemi; Roohi, Amir H.; Gollo, M. Hoseinpour; Shahabad, Sh. Imani

2018-01-01

In the 3D laser forming process, developing an appropriate laser scan pattern for producing specimens with high quality and uniformity is critical. This study presents certain principles for developing scan paths. Seven scan path parameters are considered, including: (1) combined linear or curved path; (2) type of combined linear path; (3) order of scan sequences; (4) the position of the start point in each scan; (5) continuous or discontinuous scan path; (6) direction of scan path; and (7) angular arrangement of combined linear scan paths. Regarding these path parameters, ten combined linear scan patterns are presented. Numerical simulations show continuous hexagonal, scan pattern, scanning from outer to inner path, is the optimized. In addition, it is observed the position of the start point and the angular arrangement of scan paths is the most effective path parameters. Also, further experimentations show four sequences due to creat symmetric condition enhance the height of the bowl-shaped products and uniformity. Finally, the optimized hexagonal pattern was compared with the similar circular one. In the hexagonal scan path, distortion value and standard deviation rather to edge height of formed specimen is very low, and the edge height despite of decreasing length of scan path increases significantly compared to the circular scan path. As a result, four-sequence hexagonal scan pattern is proposed as the optimized perimeter scan path to produce bowl-shaped product.

76 FR 61709 - Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Form 3728...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0708] Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Form 3728, Animal...: The Food and Drug Administration (FDA) is announcing an opportunity for public comment on the proposed...

21 CFR 830.120 - Responsibilities of an FDA-accredited issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Responsibilities of an FDA-accredited issuing... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA Accreditation of an Issuing Agency § 830.120 Responsibilities of an FDA-accredited issuing agency. To maintain its accreditation, an...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 314.108 - New drug product exclusivity.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and... investigation means that before or during the investigation, the applicant was named in Form FDA-1571 filed with FDA as the sponsor of the investigational new drug application under which the investigation was...

77 FR 51949 - Privacy Act, Exempt Record System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

.... FDA-2011-N-0252] Office of the Secretary 45 CFR Part 5b Privacy Act, Exempt Record System AGENCY... Drug Administration (FDA) of the Department of Health and Human Services (HHS) will be implementing a new system of records, 09-10-0020, ``FDA Records Related to Research Misconduct Proceedings, HHS/FDA...

21 CFR 314.96 - Amendments to an unapproved abbreviated application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... applicant on the same drug product formulation, unless the information has previously been submitted to FDA... and FDA determines that there may be bioequivalence issues or concerns with the product, FDA may...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

Internet Database Review: The FDA BBS.

ERIC Educational Resources Information Center

Tomaiuolo, Nicholas G.

1993-01-01

Describes the electronic bulletin board system (BBS) of the Food and Drug Administration (FDA) that is accessible through the Internet. Highlights include how to gain access; the menu-driven software; other electronic sources of FDA information; and adding value. Examples of the FDA BBS menu and the help screen are included. (LRW)

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

77 FR 14401 - Draft Guidance on Drug Safety Information-FDA's Communication to the Public; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2005-D-0339] Draft Guidance on Drug Safety Information--FDA's Communication to the Public; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

78 FR 36194 - Draft Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0490] Draft Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 314.96 - Amendments to an unapproved abbreviated application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... applicant on the same drug product formulation, unless the information has previously been submitted to FDA... and FDA determines that there may be bioequivalence issues or concerns with the product, FDA may...

Level 2 validation of a flow cytometric method for detection of Escherichia coli O157:H7 in raw spinach.

PubMed

Williams, Anna J; Cooper, Willie M; Summage-West, Christine V; Sims, Lillie M; Woodruff, Robert; Christman, Jessica; Moskal, Ted J; Ramsaroop, Shawn; Sutherland, John B; Alusta, Pierre; Wilkes, Jon G; Buzatu, Dan A

2015-12-23

The Bacteriological Analytical Manual (BAM) method currently used by the United States Food and Drug Administration (FDA) to detect Escherichia coli O157:H7 in spinach was systematically compared to a new flow cytometry based method. This Food and Drug Administration (FDA) level 2 external laboratory validation study was designed to determine the latter method's sensitivity and speed for analysis of this pathogen in raw spinach. Detection of target cell inoculations with a low cell count is critical, since enterohemorrhagic strains of E. coli require an infective dose of as few as 10 cells (Schmid-Hempel and Frank, 2007). Although, according to the FDA, the infectious dose is unknown (Food and Drug Administration, 1993). Therefore, the inoculation level into the spinach, a total of 2.0±2.6 viable E. coli O157 cells, was specified to yield between 25% and 75% detection by the new method, out of 20 samples (10 positives and 10 negatives). This criterion was met in that the new method detected 60% of the nominally positive samples; the corresponding sensitivity of the reference method was 50%. For both methods the most likely explanation for false negatives was that no viable cells were actually introduced into the sample. In this validation study, the flow cytometry method was equal to the BAM in sensitivity and far superior in speed. Published by Elsevier B.V.

Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection.

PubMed

Tummers, Willemieke S; Warram, Jason M; Tipirneni, Kiranya E; Fengler, John; Jacobs, Paula; Shankar, Lalitha; Henderson, Lori; Ballard, Betsy; Pogue, Brian W; Weichert, Jamey P; Bouvet, Michael; Sorger, Jonathan; Contag, Christopher H; Frangioni, John V; Tweedle, Michael F; Basilion, James P; Gambhir, Sanjiv S; Rosenthal, Eben L

2017-05-01

Considerable advances in cancer-specific optical imaging have improved the precision of tumor resection. In comparison to traditional imaging modalities, this technology is unique in its ability to provide real-time feedback to the operating surgeon. Given the significant clinical implications of optical imaging, there is an urgent need to standardize surgical navigation tools and contrast agents to facilitate swift regulatory approval. Because fluorescence-enhanced surgery requires a combination of both device and drug, each may be developed in conjunction, or separately, which are important considerations in the approval process. This report is the result of a one-day meeting held on May 4, 2016 with officials from the National Cancer Institute, the FDA, members of the American Society of Image-Guided Surgery, and members of the World Molecular Imaging Society, which discussed consensus methods for FDA-directed human testing and approval of investigational optical imaging devices as well as contrast agents for surgical applications. The goal of this workshop was to discuss FDA approval requirements and the expectations for approval of these novel drugs and devices, packaged separately or in combination, within the context of optical surgical navigation. In addition, the workshop acted to provide clarity to the research community on data collection and trial design. Reported here are the specific discussion items and recommendations from this critical and timely meeting. Cancer Res; 77(9); 2197-206. ©2017 AACR . ©2017 American Association for Cancer Research.

Understanding Philip Morris's pursuit of US government regulation of tobacco

PubMed Central

McDaniel, P; Malone, R

2005-01-01

Objective: To investigate Philip Morris's support of US Food and Drug Administration (FDA) regulation of tobacco products and analyse its relationship to the company's image enhancement strategies. Data sources: Internal Philip Morris documents released as part of the Master Settlement Agreement. Methods: Searches of the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) beginning with such terms as "FDA" and "regulatory strategy" and expanding to include relevant new terms. Results: Philip Morris's support for government regulation of tobacco is part of a broader effort to address its negative public image, which has a damaging impact on the company's stock price, political influence, and employee morale. Through regulation, the company seeks to enhance its legitimacy, redefine itself as socially responsible, and alter the litigation environment. Whereas health advocates frame tobacco use as a public health policy issue, Philip Morris's regulatory efforts focus on framing tobacco use as an individual choice by informed adults to use a risky product. This framing allows Philip Morris to portray itself as a reasonable and responsible manufacturer and marketer of risky products. Conclusions: Philip Morris's ability to improve its image through support of FDA regulation may undermine tobacco control efforts aimed at delegitimising the tobacco industry. It may also create the impression that Philip Morris's products are being made safer and ultimately protect the company from litigation. While strong regulation of tobacco products and promotion remain critical public health goals, previous experiences with tobacco regulation show that caution may be warranted. PMID:15923470

Understanding Philip Morris's pursuit of US government regulation of tobacco.

PubMed

McDaniel, P A; Malone, R E

2005-06-01

To investigate Philip Morris's support of US Food and Drug Administration (FDA) regulation of tobacco products and analyse its relationship to the company's image enhancement strategies. Internal Philip Morris documents released as part of the Master Settlement Agreement. Searches of the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) beginning with such terms as "FDA" and "regulatory strategy" and expanding to include relevant new terms. Philip Morris's support for government regulation of tobacco is part of a broader effort to address its negative public image, which has a damaging impact on the company's stock price, political influence, and employee morale. Through regulation, the company seeks to enhance its legitimacy, redefine itself as socially responsible, and alter the litigation environment. Whereas health advocates frame tobacco use as a public health policy issue, Philip Morris's regulatory efforts focus on framing tobacco use as an individual choice by informed adults to use a risky product. This framing allows Philip Morris to portray itself as a reasonable and responsible manufacturer and marketer of risky products. Philip Morris's ability to improve its image through support of FDA regulation may undermine tobacco control efforts aimed at delegitimising the tobacco industry. It may also create the impression that Philip Morris's products are being made safer and ultimately protect the company from litigation. While strong regulation of tobacco products and promotion remain critical public health goals, previous experiences with tobacco regulation show that caution may be warranted.

Development Considerations for Nanocrystal Drug Products.

PubMed

Chen, Mei-Ling; John, Mathew; Lee, Sau L; Tyner, Katherine M

2017-05-01

Nanocrystal technology has emerged as a valuable tool for facilitating the delivery of poorly water-soluble active pharmaceutical ingredients (APIs) and enhancing API bioavailability. To date, the US Food and Drug Administration (FDA) has received over 80 applications for drug products containing nanocrystals. These products can be delivered by different routes of administration and are used in a variety of therapeutic areas. To aid in identifying key developmental considerations for these products, a retrospective analysis was performed on the submissions received by the FDA to date. Over 60% of the submissions were for the oral route of administration. Based on the Biopharmaceutics Classification System (BCS), most nanocrystal drugs submitted to the FDA are class II compounds that possess low aqueous solubility and high intestinal permeability. Impact of food on drug bioavailability was reduced for most nanocrystal formulations as compared with their micronized counterparts. For all routes of administration, dose proportionality was observed for some, but not all, nanocrystal products. Particular emphasis in the development of nanocrystal products was placed on the in-process tests and controls at critical manufacturing steps (such as milling process), mitigation and control of process-related impurities, and the stability of APIs or polymorphic form (s) during manufacturing and upon storage. This emphasis resulted in identifying challenges to the development of these products including accurate determination of particle size (distribution) of drug substance and/or nanocrystal colloidal dispersion, identification of polymorphic form (s), and establishment of drug substance/product specifications.

Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor

PubMed Central

Sainz, Bruno; Barretto, Naina; Martin, Danyelle N.; Hiraga, Nobuhiko; Imamura, Michio; Hussain, Snawar; Marsh, Katherine A.; Yu, Xuemei; Chayama, Kazuaki; Alrefai, Waddah A.; Uprichard, Susan L.

2011-01-01

Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. With ~170 million individuals infected and current interferon-based treatment having toxic side-effects and marginal efficacy, more effective antivirals are critically needed1. Although HCV protease inhibitors were just FDA approved, analogous to HIV therapy, optimal HCV therapy likely will require a combination of antivirals targeting multiple aspects of the viral lifecycle. Viral entry represents a promising multi-faceted target for antiviral intervention; however, to date FDA-approved inhibitors of HCV cell entry are unavailable. Here we show that the cellular Niemann-Pick C1-Like 1 (NPC1L1) cholesterol uptake receptor is an HCV entry factor amendable to therapeutic intervention. Specifically, NPC1L1 expression is necessary for HCV infection as silencing or antibody-mediated blocking of NPC1L1 impairs cell-cultured-derived HCV (HCVcc) infection initiation. In addition, the clinically-available FDA-approved NPC1L1 antagonist ezetimibe2,3 potently blocks HCV uptake in vitro via a virion cholesterol-dependent step prior to virion-cell membrane fusion. Importantly, ezetimibe inhibits infection of all major HCV genotypes in vitro, and in vivo delays the establishment of HCV genotype 1b infection in mice with human liver grafts. Thus, we have not only identified NPC1L1 as an HCV cell entry factor, but also discovered a new antiviral target and potential therapeutic agent. PMID:22231557

Translating New Science Into the Drug Review Process

PubMed Central

Rouse, Rodney; Kruhlak, Naomi; Weaver, James; Burkhart, Keith; Patel, Vikram; Strauss, David G.

2017-01-01

In 2011, the US Food and drug Administration (FDA) developed a strategic plan for regulatory science that focuses on developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. In line with this, the Division of Applied Regulatory Science was created to move new science into the Center for Drug Evaluation and Research (CDER) review process and close the gap between scientific innovation and drug review. The Division, located in the Office of Clinical Pharmacology, is unique in that it performs mission-critical applied research and review across the translational research spectrum including in vitro and in vivo laboratory research, in silico computational modeling and informatics, and integrated clinical research covering clinical pharmacology, experimental medicine, and postmarket analyses. The Division collaborates with Offices throughout CDER, across the FDA, other government agencies, academia, and industry. The Division is able to rapidly form interdisciplinary teams of pharmacologists, biologists, chemists, computational scientists, and clinicians to respond to challenging regulatory questions for specific review issues and for longer-range projects requiring the development of predictive models, tools, and biomarkers to speed the development and regulatory evaluation of safe and effective drugs. This article reviews the Division’s recent work and future directions, highlighting development and validation of biomarkers; novel humanized animal models; translational predictive safety combining in vitro, in silico, and in vivo clinical biomarkers; chemical and biomedical informatics tools for safety predictions; novel approaches to speed the development of complex generic drugs, biosimilars, and antibiotics; and precision medicine. PMID:29568713

Company stock prices before and after public announcements related to oncology drugs.

PubMed

Rothenstein, Jeffrey M; Tomlinson, George; Tannock, Ian F; Detsky, Allan S

2011-10-19

Phase III clinical trials and Food and Drug Administration (FDA) regulatory decisions are critical for success of new drugs and can influence a company's market valuation. Knowledge of trial results before they are made public (ie, "inside information") can affect the price of a drug company's stock. We examined the stock prices of companies before and after public announcements regarding experimental anticancer drugs owned by the companies. We identified drugs that were undergoing evaluation in phase III trials or for regulatory approval by the US FDA from January 2000 to January 2009. Stock prices of companies that owned such drugs were analyzed for 120 trading days before and after the first public announcement of 1) results of clinical trials with positive and negative outcomes and 2) positive and negative regulatory decisions. All statistical tests were two-sided. We identified public announcements from 23 positive trials and 36 negative trials and from 41 positive and nine negative FDA regulatory decisions. The mean stock price for the 120 trading days before a phase III clinical trial announcement increased by 13.7% (95% confidence interval = -2.2% to 29.6%) for companies that reported positive trials and decreased by 0.7% (95% confidence interval = -13.8% to 12.3%) for companies that reported negative trials (P = .09). In a post hoc analysis comparing the stock price averaged over 60 trading days before and after day -60 relative to the clinical trial announcement, the mean stock price increased by 9.4% for companies that reported positive trials and decreased by 4.5% for companies that reported negative trials (P = .03). Changes in company stock prices before FDA regulatory decisions did not differ statistically between companies with positive decision and companies with negative decisions. Trends in company stock prices before the first public announcement differ for companies that report positive vs negative trials. This finding has important legal and ethical implications for investigators, drug companies, and the investment industry.

Safety and efficacy of peramivir for influenza treatment

PubMed Central

Hata, Atsuko; Akashi-Ueda, Ryoko; Takamatsu, Kazufumi; Matsumura, Takuro

2014-01-01

Objective This report presents a review of the efficacy and safety of peramivir, a neuraminidase inhibitor that was granted Emergency Use Authorization by the US Food and Drug Administration (FDA) from October 23, 2009 to June 23, 2010 during the 2009 H1N1 pandemic. Methods Literature was accessed via PubMed (January 2000–April 2014) using several search terms: peramivir; BCX-1812; RWJ 270201; H1N1, influenza; antivirals; and neuraminidase inhibitors. The peramivir manufacturers, Shionogi and Co Ltd and BioCryst Pharmaceuticals, were contacted to obtain unpublished data and information presented at recent scientific meetings. Information was obtained from the Centers for Disease Control and Prevention (CDC) and from US FDA websites. English-language and Japanese-language reports in the literature were reviewed and selected based on relevance, along with information from the CDC, US FDA, and the drug manufacturers. Results We obtained eleven clinical trial reports of intravenous peramivir, two of which described comparisons with oseltamivir. Seven of nine other recently reported published studies was a dose–response study. Clinical reports of critically ill patients and pediatric patients infected with pandemic H1N1 described that early treatment significantly decreased mortality. Peramivir administered at 300 mg once daily in adult patients with influenza significantly reduces the time to alleviation of symptoms or fever compared to placebo. It is likely to be as effective as other neuraminidase inhibitors. Conclusion Although peramivir shows efficacy for the treatment of seasonal and pH1N1 influenza, it has not received US FDA approval. Peramivir is used safely and efficiently in hospitalized adult and pediatric patients with suspected or laboratory-confirmed influenza. Peramivir might be a beneficial alternative antiviral treatment for many patients, including those unable to receive inhaled or oral neuraminidase inhibitors, or those requiring nonintravenous drug delivery. PMID:25368514

Using mobile health technology to deliver decision support for self-monitoring after lung transplantation.

PubMed

Jiang, Yun; Sereika, Susan M; DeVito Dabbs, Annette; Handler, Steven M; Schlenk, Elizabeth A

2016-10-01

Lung transplant recipients (LTR) experience problems recognizing and reporting critical condition changes during their daily health self-monitoring. Pocket PATH(®), a mobile health application, was designed to provide automatic feedback messages to LTR to guide decisions for detecting and reporting critical values of health indicators. To examine the degree to which LTR followed decision support messages to report recorded critical values, and to explore predictors of appropriately following technology decision support by reporting critical values during the first year after transplantation. A cross-sectional correlational study was conducted to analyze existing data from 96 LTR who used the Pocket PATH for daily health self-monitoring. When a critical value is entered, the device automatically generated a feedback message to guide LTR about when and what to report to their transplant coordinators. Their socio-demographics and clinical characteristics were obtained before discharge. Their use of Pocket PATH for health self-monitoring during 12 months was categorized as low (≤25% of days), moderate (>25% to ≤75% of days), and high (>75% of days) use. Following technology decision support was defined by the total number of critical feedback messages appropriately handled divided by the total number of critical feedback messages generated. This variable was dichotomized by whether or not all (100%) feedback messages were appropriately followed. Binary logistic regression was used to explore predictors of appropriately following decision support. Of the 96 participants, 53 had at least 1 critical feedback message generated during 12 months. Of these 53 participants, the average message response rate was 90% and 33 (62%) followed 100% decision support. LTR who moderately used Pocket PATH (n=23) were less likely to follow technology decision support than the high (odds ratio [OR]=0.11, p=0.02) and low (OR=0.04, p=0.02) use groups. The odds of following decision support were reduced in LTR whose income met basic needs (OR=0.01, p=0.01) or who had longer hospital stays (OR=0.94, p=0.004). A significant interaction was found between gender and past technology experience (OR=0.21, p=0.03), suggesting that with increased past technology experience, the odds of following decision support to report all critical values decreased in men but increased in women. The majority of LTR responded appropriately to mobile technology-based decision support for reporting recorded critical values. Appropriately following technology decision support was associated with gender, income, experience with technology, length of hospital stay, and frequency of use of technology for self-monitoring. Clinicians should monitor LTR, who are at risk for poor reporting of recorded critical values, more vigilantly even when LTR are provided with mobile technology decision support. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Proactive routing mutation against stealthy Distributed Denial of Service attacks: metrics, modeling, and analysis

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

Duan, Qi; Al-Shaer, Ehab; Chatterjee, Samrat

The Infrastructure Distributed Denial of Service (IDDoS) attacks continue to be one of the most devastating challenges facing cyber systems. The new generation of IDDoS attacks exploit the inherent weakness of cyber infrastructure including deterministic nature of routes, skew distribution of flows, and Internet ossification to discover the network critical links and launch highly stealthy flooding attacks that are not observable at the victim end. In this paper, first, we propose a new metric to quantitatively measure the potential susceptibility of any arbitrary target server or domain to stealthy IDDoS attacks, and es- timate the impact of such susceptibility onmore » enterprises. Second, we develop a proactive route mutation technique to minimize the susceptibility to these attacks by dynamically changing the flow paths periodically to invalidate the adversary knowledge about the network and avoid targeted critical links. Our proposed approach actively changes these network paths while satisfying security and qualify of service requirements. We present an integrated approach of proactive route mutation that combines both infrastructure-based mutation that is based on reconfiguration of switches and routers, and middle-box approach that uses an overlay of end-point proxies to construct a virtual network path free of critical links to reach a destination. We implemented the proactive path mutation technique on a Software Defined Network using the OpendDaylight controller to demonstrate a feasible deployment of this approach. Our evaluation validates the correctness, effectiveness, and scalability of the proposed approaches.« less

Controlling Low-Rate Signal Path Microdischarge for an Ultra-Low-Background Proportional Counter

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

Mace, Emily K.; Aalseth, Craig E.; Bonicalzi, Ricco

2013-05-01

ABSTRACT Pacific Northwest National Laboratory (PNNL) has developed an ultra-low-background proportional counter (ULBPC) made of high purity copper. These detectors are part of an ultra-low-background counting system (ULBCS) in the newly constructed shallow underground laboratory at PNNL (at a depth of ~30 meters water-equivalent). To control backgrounds, the current preamplifier electronics are located outside the ULBCS shielding. Thus the signal from the detector travels through ~1 meter of cable and is potentially susceptible to high voltage microdischarge and other sources of electronic noise. Based on initial successful tests, commercial cables and connectors were used for this critical signal path. Subsequentmore » testing across different batches of commercial cables and connectors, however, showed unwanted (but still low) rates of microdischarge noise. To control this noise source, two approaches were pursued: first, to carefully validate cables, connectors, and other commercial components in this critical signal path, making modifications where necessary; second, to develop a custom low-noise, low-background preamplifier that can be integrated with the ULBPC and thus remove most commercial components from the critical signal path. This integrated preamplifier approach is based on the Amptek A250 low-noise charge-integrating preamplifier module. The initial microdischarge signals observed are presented and characterized according to the suspected source. Each of the approaches for mitigation is described, and the results from both are compared with each other and with the original performance seen with commercial cables and connectors.« less

Agenda: EDRN FDA Education Workshop — EDRN Public Portal

Cancer.gov

The purpose of this workshop was to open dialogue between FDA staff that provide oversight for review of in vitro diagnostic applications and EDRN scientists currently performing clinical validation studies on cancer biomarkers. Issues related to FDA review of diagnostic tests were presented by FDA personnel. Representatives from EDRN provided details on supporting data of their validation studies and the resources developed within EDRN to facilitate such research for FDA compliance. The agenda provided here provides links to the presentations by each speaker.

An Optimization-Driven Analysis Pipeline to Uncover Biomarkers and Signaling Paths: Cervix Cancer.

PubMed

Lorenzo, Enery; Camacho-Caceres, Katia; Ropelewski, Alexander J; Rosas, Juan; Ortiz-Mojer, Michael; Perez-Marty, Lynn; Irizarry, Juan; Gonzalez, Valerie; Rodríguez, Jesús A; Cabrera-Rios, Mauricio; Isaza, Clara

2015-06-01

Establishing how a series of potentially important genes might relate to each other is relevant to understand the origin and evolution of illnesses, such as cancer. High-throughput biological experiments have played a critical role in providing information in this regard. A special challenge, however, is that of trying to conciliate information from separate microarray experiments to build a potential genetic signaling path. This work proposes a two-step analysis pipeline, based on optimization, to approach meta-analysis aiming to build a proxy for a genetic signaling path.

The debate on FDA reform: a view from the U.S. Senate. Food and Drug Administration.

PubMed

Baker, R

1995-09-01

The recently released concept paper on Food and Drug Administration (FDA) reform from Republican Senator, Nancy Kassebaum, is reviewed. Senator Kassebaum chairs the Senate Committee on Labor and Human Resources that will influence the Senate's action on FDA reform. The paper outlines the Senator's priorities for Congressional legislation on FDA reform in the following areas: the FDA mission and its accountability; creation of a Performance Review Panel and Industry Advisory Council; approval and access of products for seriously ill patients; the FDA's responsibility for good manufacturing practices; establishment of an Ombudsman Office for resolving disputes; dissemination of information on unapproved uses of approved products; and approval standards for new drugs.

Use of data mining at the Food and Drug Administration.

PubMed

Duggirala, Hesha J; Tonning, Joseph M; Smith, Ella; Bright, Roselie A; Baker, John D; Ball, Robert; Bell, Carlos; Bright-Ponte, Susan J; Botsis, Taxiarchis; Bouri, Khaled; Boyer, Marc; Burkhart, Keith; Condrey, G Steven; Chen, James J; Chirtel, Stuart; Filice, Ross W; Francis, Henry; Jiang, Hongying; Levine, Jonathan; Martin, David; Oladipo, Taiye; O'Neill, Rene; Palmer, Lee Anne M; Paredes, Antonio; Rochester, George; Sholtes, Deborah; Szarfman, Ana; Wong, Hui-Lee; Xu, Zhiheng; Kass-Hout, Taha

2016-03-01

This article summarizes past and current data mining activities at the United States Food and Drug Administration (FDA). We address data miners in all sectors, anyone interested in the safety of products regulated by the FDA (predominantly medical products, food, veterinary products and nutrition, and tobacco products), and those interested in FDA activities. Topics include routine and developmental data mining activities, short descriptions of mined FDA data, advantages and challenges of data mining at the FDA, and future directions of data mining at the FDA. Published by Oxford University Press on behalf of the American Medical Informatics Association 2015. This work is written by US Government employees and is in the public domain in the US.

A review of the FDA draft guidance document for software validation: guidance for industry.

PubMed

Keatley, K L

1999-01-01

A Draft Guidance Document (Version 1.1) was issued by the United States Food and Drug Administration (FDA) to address the software validation requirement of the Quality System Regulation, 21 CFR Part 820, effective June 1, 1997. The guidance document outlines validation considerations that the FDA regards as applicable to both medical device software and software used to "design, develop or manufacture" medical devices. The Draft Guidance is available at the FDA web site http:@www.fda.gov/cdrh/comps/swareval++ +.html. Presented here is a review of the main features of the FDA document for Quality System Regulation (QSR), and some guidance for its implementation in industry.

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

76 FR 31615 - Draft Guidance for Industry and FDA Staff: Commercially Distributed In Vitro Diagnostic Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0305] Draft Guidance for Industry and FDA Staff: Commercially Distributed In Vitro Diagnostic Products Labeled...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

77 FR 11553 - Draft Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0080... Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled ``FDA... that address nearly all aspects of the FDA approval and surveillance processes, including application...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 830.110 - Application for accreditation as an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA Accreditation of an Issuing Agency.... (1) An applicant seeking initial FDA accreditation as an issuing agency shall notify FDA of its desire to be accredited by sending a notification by email to [email protected]fda.hhs.gov, or by correspondence to...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

29 CFR 1987.108 - Role of Federal agencies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) PROCEDURES FOR HANDLING RETALIATION COMPLAINTS UNDER SECTION 402 OF THE FDA FOOD SAFETY...) The FDA, if interested in a proceeding, may participate as amicus curiae at any time in the proceeding, at the FDA's discretion. At the request of the FDA, copies of all documents in a case must be sent to...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

76 FR 32367 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1999-D-0742 (formerly Docket No. 1999D-4396)] Draft Guidance for Clinical Investigators, Industry, and FDA Staff...: Notice; correction. SUMMARY: The Food and Drug Administration (FDA) is correcting a notice that appeared...

78 FR 29141 - Center for Devices and Radiological Health Appeals Processes; Guidance for Industry and FDA Staff...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0893] Center for Devices and Radiological Health Appeals Processes; Guidance for Industry and FDA Staff... Administration (FDA) is announcing the availability of the guidance entitled ``Center for Devices and...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 801.57 - Discontinuation of legacy FDA identification numbers assigned to devices.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Discontinuation of legacy FDA identification... Device Identification § 801.57 Discontinuation of legacy FDA identification numbers assigned to devices... been assigned an FDA labeler code to facilitate use of NHRIC or NDC numbers may continue to use that...

78 FR 19492 - Draft Guidance for Industry on Formal Meetings Between FDA and Biosimilar Biological Product...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0286] Draft Guidance for Industry on Formal Meetings Between FDA and Biosimilar Biological Product Sponsors or... Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

75 FR 11893 - Food and Drug Administration Transparency Task Force; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247... Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food and Drug Administration (FDA) is soliciting comments from interested persons on ways in which FDA can increase transparency between FDA and...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0080... and Drug Administration (FDA) is announcing the availability of a guidance entitled ``FDA Oversight of... nearly all aspects of the FDA approval and surveillance processes, including application submission...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

76 FR 41506 - Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0215] Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

76 FR 56205 - Request for Notification From Industry Organizations Interested in Participating in the Selection...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... Products Scientific Advisory Committee, notify FDA in writing. FDA is also requesting nominations for... letters stating interest in participating in the selection process to FDA by October 12, 2011 (see... candidates should be sent to FDA by October 12, 2011. ADDRESSES: All letters of interest and nominations...

EBOLA and FDA: reviewing the response to the 2014 outbreak, to find lessons for the future

PubMed Central

Largent, Emily A.

2016-01-01

Abstract In 2014, West Africa confronted the most severe outbreak of Ebola virus disease (EVD) in history. At the onset of the outbreak—as now—there were no therapies approved by the U.S. Food and Drug Administration (FDA) for prevention of, post-exposure prophylaxis against, or treatment of EVD. As a result, the outbreak spurred interest in developing novel treatments, sparked calls to use experimental interventions in the field, and highlighted challenges to the standard approach to FDA approval of new drugs. Although the outbreak was geographically centered in West Africa, it showcased FDA's global role in drug development, approval, and access. FDA's response to EVD highlights the panoply of agency powers and demonstrates the flexibility of FDA's regulatory framework. This paper evaluates the strengths and weaknesses of FDA's response and makes policy recommendations regarding how FDA should respond to new and re-emerging public health threats. In particular, it argues that greater emphasis should be placed on drug development in interoutbreak periods and on assuring access to approved products. The current pandemic of Zika virus infection is but one example of an emerging health threat that will require FDA involvement in order to achieve a successful response. PMID:28852537

Limitations in the Use of Fluorescein Diacetate/Propidium Iodide (FDA/PI) and Cell Permeable Nucleic Acid Stains for Viability Measurements of Isolated Islets of Langerhans.

PubMed

Boyd, Vinc; Cholewa, Olivia Maria; Papas, Klearchos K

2008-03-01

BACKGROUND: A review of current literature shows that the combined use of the cell permeable esterase-substrate fluorescein diacetate (FDA) and the cell impermeant nucleic acid stain propidium iodide (PI) to be one of the most common fluorescence-based methods to assess the viability of isolated islets of Langerhans, and it is currently used for islet product release prior to transplantation in humans. However, results from this assay do not correlate with islet viability and function or islet transplantation success in animals or humans (Eckhard et al. 2004; Ricordi et al. 2001). This may be in part attributed to considerable differences as well as discrepancies in the use of these reagents on islets. We critically surveyed the literature and evaluated the impact of a number of variables associated with the use of FDA/PI to determine their reliability in assessing islet cell viability. In addition, we evaluated other fluorescent stains, such as SYTO(R)13, SYTO(R)24 and SYBR(R)14 as possible alternatives to FDA. RESULTS: We found that the stability of stains in storage and stock solutions, the number of islets stained, concentration of stains, staining incubation time, the buffer/media used, and the method of examining islets were significant in the final scoring of viability. For archival file photos, the exposure time and camera/software settings can also impact interpretation of viability. Although our results show that FDA does detect intracellular esterase activity and staining with PI does assess cell membrane integrity, the results obtained from using these stains did not correlate directly with expected islet function and viability per transplantation into diabetic athymic nude mice (Papas et al. 2007). In addition, the use of two nucleic acid stains, such as SYTO(R)13 and PI, for live/dead scoring exhibited staining anomalies which limit their accuracy in assessing islet viability. CONCLUSIONS: From a review of the literature and from our observations on the impact of reagent handling and various staining and imaging parameters used to visually evaluate islets, consistent interpretation of islet cell membrane integrity and viability is dependent upon a number of factors. We discuss the utility and limitations of these reagents in evaluating islet cell membrane integrity and viability.

Limitations in the Use of Fluorescein Diacetate/Propidium Iodide (FDA/PI) and Cell Permeable Nucleic Acid Stains for Viability Measurements of Isolated Islets of Langerhans

PubMed Central

Boyd, Vinc; Cholewa, Olivia Maria; Papas, Klearchos K.

2010-01-01

Background A review of current literature shows that the combined use of the cell permeable esterase-substrate fluorescein diacetate (FDA) and the cell impermeant nucleic acid stain propidium iodide (PI) to be one of the most common fluorescence-based methods to assess the viability of isolated islets of Langerhans, and it is currently used for islet product release prior to transplantation in humans. However, results from this assay do not correlate with islet viability and function or islet transplantation success in animals or humans (Eckhard et al. 2004; Ricordi et al. 2001). This may be in part attributed to considerable differences as well as discrepancies in the use of these reagents on islets. We critically surveyed the literature and evaluated the impact of a number of variables associated with the use of FDA/PI to determine their reliability in assessing islet cell viability. In addition, we evaluated other fluorescent stains, such as SYTO®13, SYTO®24 and SYBR®14 as possible alternatives to FDA. Results We found that the stability of stains in storage and stock solutions, the number of islets stained, concentration of stains, staining incubation time, the buffer/media used, and the method of examining islets were significant in the final scoring of viability. For archival file photos, the exposure time and camera/software settings can also impact interpretation of viability. Although our results show that FDA does detect intracellular esterase activity and staining with PI does assess cell membrane integrity, the results obtained from using these stains did not correlate directly with expected islet function and viability per transplantation into diabetic athymic nude mice (Papas et al. 2007). In addition, the use of two nucleic acid stains, such as SYTO®13 and PI, for live/dead scoring exhibited staining anomalies which limit their accuracy in assessing islet viability. Conclusions From a review of the literature and from our observations on the impact of reagent handling and various staining and imaging parameters used to visually evaluate islets, consistent interpretation of islet cell membrane integrity and viability is dependent upon a number of factors. We discuss the utility and limitations of these reagents in evaluating islet cell membrane integrity and viability. PMID:20814586

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.

Association of the FDA Amendment Act with trial registration, publication, and outcome reporting.

PubMed

Phillips, Adam T; Desai, Nihar R; Krumholz, Harlan M; Zou, Constance X; Miller, Jennifer E; Ross, Joseph S

2017-07-18

Selective clinical trial publication and outcome reporting has the potential to bias the medical literature. The 2007 Food and Drug Administration (FDA) Amendment Act (FDAAA) mandated clinical trial registration and outcome reporting on ClinicalTrials.gov, a publicly accessible trial registry. Using publicly available data from ClinicalTrials.gov, FDA documents, and PubMed, we determined registration, publication, and reporting of findings for all efficacy trials supporting FDA approval of new drugs for cardiovascular disease and diabetes between 2005 and 2014, before and after the FDAAA. For published trials, we compared the published interpretation of the findings (positive, equivocal, or negative) with the FDA reviewer's interpretation. Between 2005 and 2014, the FDA approved 30 drugs for 32 indications of cardiovascular disease (n = 17) and diabetes (n = 15) on the basis of 183 trials (median per indication 5.7 (IQR, 3-8)). Compared with pre FDAAA, post-FDAAA studies were more likely to be registered (78 of 78 (100%) vs 73 of 105 (70%); p < 0.001), to be published (76 of 78 (97%) vs 93 of 105 (89%); p = 0.03), and to present findings concordant with the FDA reviewer's interpretation (74 of 76 (97%) vs 78 of 93 (84%); p = 0.004). Pre FDAAA, the FDA reviewer interpreted 80 (76%) trials as positive and 91 (98%) were published as positive. Post FDAAA, the FDA reviewer interpreted 71 (91%) trials as positive and 71 (93%) were published as positive. FDAAA was associated with increased registration, publication, and FDA-concordant outcome reporting for trials supporting FDA approval of new drugs for cardiovascular disease and diabetes.

Spin in RCTs of anxiety medication with a positive primary outcome: a comparison of concerns expressed by the US FDA and in the published literature.

PubMed

Beijers, Lian; Jeronimus, Bertus F; Turner, Erick H; de Jonge, Peter; Roest, Annelieke M

2017-03-29

This study aimed to determine the presence of spin in papers on positive randomised clinical trials (RCTs) of antidepressant medication for anxiety disorders by comparing concerns expressed in the Food and Drug Administration (FDA) reviews with those expressed in the published paper. For every positive anxiety medication trial with a matching publication (n=41), two independent reviewers identified the concerns raised in the US FDA reviews and those in the published literature. Spin was identified when concerns or limitations were expressed by the FDA (about the efficacy of the study drug) but not in the corresponding published paper. Concerns mentioned in the papers but not by the FDA were scored as 'non-FDA' concerns. Only six out of 35 (17%) of the FDA concerns pertaining to drug efficacy were reported in the papers. Two papers mentioned a concern that fit the FDA categories, but was not mentioned in the corresponding FDA review. Eighty-seven non-FDA concerns were counted, which often reflected general concerns or concerns related to the study design. Results indicate the presence of substantial spin in the clinical trial literature on drugs for anxiety disorders. In papers describing RCTs on anxiety medication, the concerns raised by the authors differed from those raised by the FDA. Published papers mentioned a large number of generic concerns about RCTs, such as a lack of long-term research and limited generalisability, while they mentioned few concerns about drug efficacy. These results warrant the promotion of independent statistical review, reporting of patient-level data, more study of spin, and an increased expectation that authors report FDA concerns. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Comparing the Impact of Course-Based and Apprentice-Based Research Experiences in a Life Science Laboratory Curriculum†

PubMed Central

Shapiro, Casey; Moberg-Parker, Jordan; Toma, Shannon; Ayon, Carlos; Zimmerman, Hilary; Roth-Johnson, Elizabeth A.; Hancock, Stephen P.; Levis-Fitzgerald, Marc; Sanders, Erin R.

2015-01-01

This four-year study describes the assessment of a bifurcated laboratory curriculum designed to provide upper-division undergraduate majors in two life science departments meaningful exposure to authentic research. The timing is critical as it provides a pathway for both directly admitted and transfer students to enter research. To fulfill their degree requirements, all majors complete one of two paths in the laboratory program. One path immerses students in scientific discovery experienced through team research projects (course-based undergraduate research experiences, or CUREs) and the other path through a mentored, independent research project (apprentice-based research experiences, or AREs). The bifurcated laboratory curriculum was structured using backwards design to help all students, irrespective of path, achieve specific learning outcomes. Over 1,000 undergraduates enrolled in the curriculum. Self-report survey results indicate that there were no significant differences in affective gains by path. Students conveyed which aspects of the curriculum were critical to their learning and development of research-oriented skills. Students’ interests in biology increased upon completion of the curriculum, inspiring a subset of CURE participants to subsequently pursue further research. A rubric-guided performance evaluation, employed to directly measure learning, revealed differences in learning gains for CURE versus ARE participants, with evidence suggesting a CURE can reduce the achievement gap between high-performing students and their peers. PMID:26751568

Forming limit strains for non-linear strain path of AA6014 aluminium sheet deformed at room temperature

NASA Astrophysics Data System (ADS)

Bressan, José Divo; Liewald, Mathias; Drotleff, Klaus

2017-10-01

Forming limit strain curves of conventional aluminium alloy AA6014 sheets after loading with non-linear strain paths are presented and compared with D-Bressan macroscopic model of sheet metal rupture by critical shear stress criterion. AA6014 exhibits good formability at room temperature and, thus, is mainly employed in car body external parts by manufacturing at room temperature. According to Weber et al., experimental bi-linear strain paths were carried out in specimens with 1mm thickness by pre-stretching in uniaxial and biaxial directions up to 5%, 10% and 20% strain levels before performing Nakajima testing experiments to obtain the forming limit strain curves, FLCs. In addition, FLCs of AA6014 were predicted by employing D-Bressan critical shear stress criterion for bi-linear strain path and comparisons with the experimental FLCs were analyzed and discussed. In order to obtain the material coefficients of plastic anisotropy, strain and strain rate hardening behavior and calibrate the D-Bressan model, tensile tests, two different strain rate on specimens cut at 0°, 45° and 90° to the rolling direction and also bulge test were carried out at room temperature. The correlation of experimental bi-linear strain path FLCs is reasonably good with the predicted limit strains from D-Bressan model, assuming equivalent pre-strain calculated by Hill 1979 yield criterion.

Enhancing the incorporation of the patient's voice in drug development and evaluation.

PubMed

Chalasani, Meghana; Vaidya, Pujita; Mullin, Theresa

2018-01-01

People living with a condition are uniquely positioned to inform the understanding of the therapeutic context for drug development and evaluation. In 2012, the U.S. Food and Drug Administration (FDA) established the Patient-Focused Drug Development (PFDD) initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. PFDD meetings are unique among FDA public meetings, with a format designed to engage patients and elicit their perspectives on two topic areas: (1) the most significant symptoms of their condition and the impact of the condition on daily life; and, (2) their current approaches to treatment. FDA has conducted 24 disease-specific PFDD meetings to date. The lessons learned from PFDD meetings range from experiences common across rare diseases to more disease specific experiences that matter most to patients. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Patient-focused drug development is an ongoing effort and FDA looks forward to the next steps in advancing the science and the utilization of patient input throughout drug development and evaluation. The U.S. Food and Drug Administration (FDA) has multiple mechanisms for its regulators and staff to interact with patients -- but none quite like its novel Patient-Focused Drug Development (PFDD) initiative. FDA established the PFDD initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. Since the initiative's inception in 2012, FDA has held 24 PFDD meetings, covering a range of disease areas and hearing directly from thousands of patients and caregivers. FDA's PFDD meetings have also provided key stakeholders, including patient advocates, researchers, drug developers, healthcare providers, and other government officials, an opportunity to hear the patient's voice. The lessons learned include but are not limited to specific experiences that matter most to patients, patient perspectives on meaningful treatment benefits and how patients want to be engaged in the drug development process. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Further enhancing the incorporation of the patient's voice in drug development and evaluation continues to be a priority for FDA.

ABLEPathPlanner library for Umbra

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

Oppel III, Fred J; Xavier, Patrick G.; Gottlieb, Eric Joseph

Umbra contains a flexible, modular path planner that is used to simulate complex entity behaviors moving within 3D terrain environments that include buildings, barriers, roads, bridges, fences, and a variety of other terrain features (water, vegetation, slope, etc…). The path planning algorithm is a critical component required to execute these tactical behaviors to provide realistic entity movement and provide efficient system computing performance.

Consistency of forest presence and biomass predictions modeled across overlapping spatial and temporal extents

Treesearch

Mark D. Nelson; Sean Healey; W. Keith Moser; J.G. Masek; Warren Cohen

2011-01-01

We assessed the consistency across space and time of spatially explicit models of forest presence and biomass in southern Missouri, USA, for adjacent, partially overlapping satellite image Path/Rows, and for coincident satellite images from the same Path/Row acquired in different years. Such consistency in satellite image-based classification and estimation is critical...

A critical transition in leaf evolution facilitated the Cretaceous angiosperm revolution.

PubMed

de Boer, Hugo Jan; Eppinga, Maarten B; Wassen, Martin J; Dekker, Stefan C

2012-01-01

The revolutionary rise of broad-leaved (flowering) angiosperm plant species during the Cretaceous initiated a global ecological transformation towards modern biodiversity. Still, the mechanisms involved in this angiosperm radiation remain enigmatic. Here we show that the period of rapid angiosperm evolution initiated after the leaf interior (post venous) transport path length for water was reduced beyond the leaf interior transport path length for CO2 at a critical leaf vein density of 2.5-5 mm mm(-2). Data and our modelling approaches indicate that surpassing this critical vein density was a pivotal moment in leaf evolution that enabled evolving angiosperms to profit from developing leaves with more and smaller stomata in terms of higher carbon returns from equal water loss. Surpassing the critical vein density may therefore have facilitated evolving angiosperms to develop leaves with higher gas exchange capacities required to adapt to the Cretaceous CO2 decline and outcompete previously dominant coniferous species in the upper canopy.

75 FR 29561 - Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004] [FDA 225-09-0012] Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com... Administration (FDA) is providing notice of a memorandum of understanding (MOU) between FDA and Drugs.Com. The...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false The Food and Drug Administration's (FDA's... (CONTINUED) FOOD ADDITIVES Premarket Notifications § 170.105 The Food and Drug Administration's (FDA's... data or other information available to FDA, including data not submitted by the manufacturer or...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

77 FR 55845 - Science Board to the Food and Drug Administration: Request for Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is requesting nominations to serve on the Science Board to FDA (Science Board). FDA seeks to include the views of women and men...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

76 FR 62073 - Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0721] Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety Modernization Act... Administration (FDA) is announcing the availability of a guidance for industry entitled ``Implementation of the...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

78 FR 5463 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... currently assessing any additional data requirements. In this regard, FDA published an Advance Notice of... report. Here, e-form FDA 3744a and reporting via the Electronic Submission Gateway are provided by FDA... January 17, 2012 (77 FR 2302), FDA published a 60-day notice requesting public comment on the proposed...

Drugs and Alcohol in Civil Aviation Accident Pilot Fatalities from 2004-2008

DTIC Science & Technology

2011-09-01

Quinine 16 0.9 19 1.1 37 2.3 42 3.1 FDA 򒾅 Salicylatesβ 96 5.2 114 6.8 41 2.6 11 0.8 FDA 򒾅 Simethicone 0 0.0 0 0.0 0 0.0 1 0.1 FDA 1996... Simethicone 0 0.0 0 0.0 0 0.0 1 0.1 FDA 1996 Triprolidine 0 0.0 0 0.0 2 0.1 2 0.1 FDA 򒾅 β – Screening Cutoff Increased in 2002 μ - Public Law

Removal of Review and Reclassification Procedures for Biological Products Licensed Prior to July 1, 1972. Final rule.

PubMed

2016-02-12

The Food and Drug Administration (FDA, the Agency, or we) is removing two regulations that prescribe procedures for FDA's review and classification of biological products licensed before July 1, 1972. FDA is taking this action because the two regulations are obsolete and no longer necessary in light of other statutory and regulatory authorities established since 1972, which allow FDA to evaluate and monitor the safety and effectiveness of all biological products. In addition, other statutory and regulatory authorities authorize FDA to revoke a license for biological products because they are not safe and effective, or are misbranded. FDA is taking this action as part of its retrospective review of its regulations to promote improvement and innovation.

Concentration-Discharge Relations in the Critical Zone: Implications for Resolving Critical Zone Structure, Function, and Evolution

NASA Astrophysics Data System (ADS)

Chorover, Jon; Derry, Louis A.; McDowell, William H.

2017-11-01

Critical zone science seeks to develop mechanistic theories that describe critical zone structure, function, and long-term evolution. One postulate is that hydrogeochemical controls on critical zone evolution can be inferred from solute discharges measured down-gradient of reactive flow paths. These flow paths have variable lengths, interfacial compositions, and residence times, and their mixing is reflected in concentration-discharge (C-Q) relations. Motivation for this special section originates from a U.S. Critical Zone Observatories workshop that was held at the University of New Hampshire, 20-22 July 2015. The workshop focused on resolving mechanistic CZ controls over surface water chemical dynamics across the full range of lithogenic (e.g., nonhydrolyzing and hydrolyzing cations and oxyanions) and bioactive solutes (e.g., organic and inorganic forms of C, N, P, and S), including dissolved and colloidal species that may cooccur for a given element. Papers submitted to this special section on "concentration-discharge relations in the critical zone" include those from authors who attended the workshop, as well as others who responded to the open solicitation. Submissions were invited that utilized information pertaining to internal, integrated catchment function (relations between hydrology, biogeochemistry, and landscape structure) to help illuminate controls on observed C-Q relations.

Innovative postmarket device evaluation using a quality registry to monitor thoracic endovascular aortic repair in the treatment of aortic dissection.

PubMed

Beck, Adam W; Lombardi, Joseph V; Abel, Dorothy B; Morales, J Pablo; Marinac-Dabic, Danica; Wang, Grace; Azizzadeh, Ali; Kern, John; Fillinger, Mark; White, Rodney; Cronenwett, Jack L; Cambria, Richard P

2017-05-01

United States Food and Drug Administration (FDA)-mandated postapproval studies have long been a mainstay of the continued evaluation of high-risk medical devices after initial marketing approval; however, these studies often present challenges related to patient/physician recruitment and retention. Retrospective single-center studies also do not fully represent the spectrum of real-world performance nor are they likely to have a sufficiently large enough sample size to detect important signals. In recent years, The FDA Center for Devices and Radiological Health has been promoting the development and use of patient registries to advance infrastructure and methodologies for medical device investigation. The FDA 2012 document, "Strengthening the National System for Medical Device Post-market Surveillance," highlighted registries as a core foundational infrastructure when linked to other complementary data sources, including embedded unique device identification. The Vascular Quality Initiative (VQI) thoracic endovascular aortic repair for type B aortic dissection project is an innovative method of using quality improvement registries to meet the needs of device evaluation after market approval. Here we report the organization and background of this project and highlight the innovation facilitated by collaboration of physicians, the FDA, and device manufacturers. This effort used an existing national network of VQI participants to capture patients undergoing thoracic endovascular aortic repair for acute type B aortic dissection within a registry that aligns with standard practice and existing quality efforts. The VQI captures detailed patient, device, and procedural data for consecutive eligible cases under the auspices of a Patient Safety Organization (PSO). Patients were divided into a 5-year follow-up group (200 acute; 200 chronic dissections) and a 1-year follow-up group (100 acute; 100 chronic). The 5-year cohort required additional imaging details, and the 1-year group required standard VQI registry data entry. The sample size of patients in each of the 5-year acute and chronic dissection arms was achieved ≤24 months of project initiation, and data capture for the 1-year follow-up group is also nearly complete. Data completeness and follow-up has been excellent, and the two FDA-approved devices for dissection are equally represented. Although the completeness of long-term follow-up is yet to be determined, the rapidity of data collection supports the use of this construct for device assessment after market approval. The alignment of this effort with routine clinical practice and ongoing quality improvement initiatives is critical and has required minimal additional effort by practitioners, thus facilitating patient inclusion. Importantly, the success and development of this unique project has helped inform FDA strategy for future device evaluation after market approval. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

OpenFDA: an innovative platform providing access to a wealth of FDA’s publicly available data

PubMed Central

Kass-Hout, Taha A; Mohebbi, Matthew; Nelsen, Hans; Baker, Adam; Levine, Jonathan; Johanson, Elaine; Bright, Roselie A

2016-01-01

Objective The objective of openFDA is to facilitate access and use of big important Food and Drug Administration public datasets by developers, researchers, and the public through harmonization of data across disparate FDA datasets provided via application programming interfaces (APIs). Materials and Methods Using cutting-edge technologies deployed on FDA’s new public cloud computing infrastructure, openFDA provides open data for easier, faster (over 300 requests per second per process), and better access to FDA datasets; open source code and documentation shared on GitHub for open community contributions of examples, apps and ideas; and infrastructure that can be adopted for other public health big data challenges. Results Since its launch on June 2, 2014, openFDA has developed four APIs for drug and device adverse events, recall information for all FDA-regulated products, and drug labeling. There have been more than 20 million API calls (more than half from outside the United States), 6000 registered users, 20,000 connected Internet Protocol addresses, and dozens of new software (mobile or web) apps developed. A case study demonstrates a use of openFDA data to understand an apparent association of a drug with an adverse event. Conclusion With easier and faster access to these datasets, consumers worldwide can learn more about FDA-regulated products. PMID:26644398

78 FR 65334 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... information, including certain labeling information, to FDA for approval to market a product in interstate... and in a form that FDA can process, review, and archive. This requirement is in addition to the....12(b) in table 1 of this document. In July 1997, FDA revised Form FDA 356h ``Application to Market a...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1.392 - Who receives a copy of the detention order?

Code of Federal Regulations, 2013 CFR

2013-04-01

... Fda Order A Detention? § 1.392 Who receives a copy of the detention order? (a) FDA must issue the... place where the article is detained, FDA must provide a copy of the detention order to the owner of the article of food if the owner's identity can be determined readily. (b) If FDA issues a detention order for...

21 CFR 1.392 - Who receives a copy of the detention order?

Code of Federal Regulations, 2012 CFR

2012-04-01

... Fda Order A Detention? § 1.392 Who receives a copy of the detention order? (a) FDA must issue the... place where the article is detained, FDA must provide a copy of the detention order to the owner of the article of food if the owner's identity can be determined readily. (b) If FDA issues a detention order for...

21 CFR 111.610 - What records must be made available to FDA?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false What records must be made available to FDA? 111... records must be made available to FDA? (a) You must have all records required under this part, or copies of such records, readily available during the retention period for inspection and copying by FDA when...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2014 CFR

2014-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

21 CFR 1.378 - What criteria does FDA use to order a detention?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false What criteria does FDA use to order a detention? 1... General Provisions § 1.378 What criteria does FDA use to order a detention? An officer or qualified employee of FDA may order the detention of any article of food that is found during an inspection...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 1.392 - Who receives a copy of the detention order?

Code of Federal Regulations, 2011 CFR

2011-04-01

... Fda Order A Detention? § 1.392 Who receives a copy of the detention order? (a) FDA must issue the... place where the article is detained, FDA must provide a copy of the detention order to the owner of the article of food if the owner's identity can be determined readily. (b) If FDA issues a detention order for...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 1.378 - What criteria does FDA use to order a detention?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false What criteria does FDA use to order a detention? 1... General Provisions § 1.378 What criteria does FDA use to order a detention? An officer or qualified employee of FDA may order the detention of any article of food that is found during an inspection...

21 CFR 111.610 - What records must be made available to FDA?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What records must be made available to FDA? 111... records must be made available to FDA? (a) You must have all records required under this part, or copies of such records, readily available during the retention period for inspection and copying by FDA when...

21 CFR 1.378 - What criteria does FDA use to order a detention?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false What criteria does FDA use to order a detention? 1... General Provisions § 1.378 What criteria does FDA use to order a detention? An officer or qualified employee of FDA may order the detention of any article of food that is found during an inspection...

21 CFR 111.610 - What records must be made available to FDA?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false What records must be made available to FDA? 111... records must be made available to FDA? (a) You must have all records required under this part, or copies of such records, readily available during the retention period for inspection and copying by FDA when...

21 CFR 1.378 - What criteria does FDA use to order a detention?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What criteria does FDA use to order a detention? 1... General Provisions § 1.378 What criteria does FDA use to order a detention? An officer or qualified employee of FDA may order the detention of any article of food that is found during an inspection...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

21 CFR 111.610 - What records must be made available to FDA?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false What records must be made available to FDA? 111... records must be made available to FDA? (a) You must have all records required under this part, or copies of such records, readily available during the retention period for inspection and copying by FDA when...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

21 CFR 1.378 - What criteria does FDA use to order a detention?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false What criteria does FDA use to order a detention? 1... General Provisions § 1.378 What criteria does FDA use to order a detention? An officer or qualified employee of FDA may order the detention of any article of food that is found during an inspection...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2011 CFR

2011-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2012 CFR

2012-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2013 CFR

2013-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 111.610 - What records must be made available to FDA?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false What records must be made available to FDA? 111... records must be made available to FDA? (a) You must have all records required under this part, or copies of such records, readily available during the retention period for inspection and copying by FDA when...

21 CFR 1.392 - Who receives a copy of the detention order?

Code of Federal Regulations, 2010 CFR

2010-04-01

... Fda Order A Detention? § 1.392 Who receives a copy of the detention order? (a) FDA must issue the... place where the article is detained, FDA must provide a copy of the detention order to the owner of the article of food if the owner's identity can be determined readily. (b) If FDA issues a detention order for...

Medicare covers the majority of FDA-approved devices and Part B drugs, but restrictions and discrepancies remain.

PubMed

Chambers, James D; May, Katherine E; Neumann, Peter J

2013-06-01

The Food and Drug Administration (FDA) and Medicare use different standards to determine, first, whether a new drug or medical device can be marketed to the public and, second, if the federal health insurance program will pay for use of the drug or device. This discrepancy creates hurdles and uncertainty for drug and device manufacturers. We analyzed discrepancies between FDA approval and Medicare national coverage determinations for sixty-nine devices and Part B drugs approved during 1999-2011. We found that Medicare covered FDA-approved drugs or devices 80 percent of the time. However, Medicare often added conditions beyond FDA approval, particularly for devices and most often restricting coverage to patients with the most severe disease. In some instances, Medicare was less restrictive than the FDA. Our findings highlight the importance for drug and device makers of anticipating Medicare's needs when conducting clinical studies to support their products. Our findings also provide important insights for the FDA's and Medicare's pilot parallel review program.

Toward a Regulatory Framework for the Waterpipe.

PubMed

Salloum, Ramzi G; Asfar, Taghrid; Maziak, Wasim

2016-10-01

Waterpipe smoking has been dramatically increasing among youth worldwide and in the United States. Despite its general association with misperceptions of reduced harm, evidence suggests this is a harmful and dependence-inducing tobacco use method that represents a threat to public health. Waterpipe products continue to be generally unregulated, which likely has contributed to their spread. The Family Smoking Prevention and Tobacco Control Act of 2009 granted the US Food and Drug Administration (FDA) the authority to regulate waterpipe products, and the FDA finalized a rule extending its authority over waterpipe products in May 2016. This critical step in addressing the alarming increase in waterpipe smoking in the United States has created urgency for research to provide the evidence needed for effective regulatory initiatives for waterpipe products. We aim to stimulate such research by providing a framework that addresses the scope of waterpipe products and their unique context and use patterns. The proposed framework identifies regulatory targets for waterpipe product components (i.e., tobacco, charcoal, and device), the waterpipe café setting, and its marketing environment dominated by Internet promotion.

Licensure strategy for pre- and post-exposure prophylaxis of biothrax vaccine: the first vaccine licensed using the FDA animal rule.

PubMed

Longstreth, Janice; Skiadopoulos, Mario H; Hopkins, Robert J

2016-12-01

The availability of a licensed anthrax vaccine that is safe, effective, and easy to administer for both pre- and post-exposure prophylaxis is critical to successfully manage and prevent potential anthrax attacks. BioThrax® (Anthrax Vaccine Adsorbed; AVA) is the only licensed anthrax vaccine in the US. Areas covered: Recent licensed improvements to BioThrax vaccine for pre-exposure prophylaxis (PrEP) have included an intramuscular (IM) five-dose schedule (in 2008) and a three-dose IM primary series at 0, 1 and 6 months (in 2012). Post-exposure prophylaxis (PEP) - three doses given subcutaneously (SC) at 0, 2, and 4 weeks - was licensed in 2015. We review the anthrax disease and vaccine literature that supported these licensure efforts. Expert commentary: This PEP licensure is the first time the FDA's Animal Rule has been used to license a vaccine. Additional improvements such as fewer vaccine doses and reduced time to protection are desirable for a PEP vaccine and are being pursued with next generation vaccine candidates.

Risk mitigation for children exposed to drugs during gestation: A critical role for animal preclinical behavioral testing.

PubMed

Zucker, Irving

2017-06-01

Many drugs with unknown safety profiles are administered to pregnant women, placing their offspring at risk. I assessed whether behavioral outcomes for children exposed during gestation to antidepressants, anxiolytics, anti-seizure, analgesic, anti-nausea and sedative medications can be predicted by more extensive animal studies than are part of the FDA approval process. Human plus rodent data were available for only 8 of 33 CNS-active drugs examined. Similar behavioral and cognitive deficits, including autism and ADHD emerged in human offspring and in animal models of these disorders after exposure to fluoxetine, valproic acid, carbamazepine, phenytoin, phenobarbital and acetaminophen. Rodent data helpful in identifying and predicting adverse effects of prenatal drug exposure in children were first generated many years after drugs were FDA-approved and administered to pregnant women. I recommend that enhanced behavioral testing of rodent offspring exposed to drugs prenatally should begin during preclinical drug evaluation and continue during Phase I clinical trials, with findings communicated to physicians and patients in drug labels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Drug recall: An incubus for pharmaceutical companies and most serious drug recall of history

PubMed Central

Nagaich, Upendra; Sadhna, Divya

2015-01-01

There has been an increasing trend in the number of prescribed and over-the-counter drug recall over the last few years. The recall is usually due to company's discovery, customer's complaint or Food and Drug Administration (FDA) observation. The process of recall involves a planned specific course of action, which addresses the depth of recall, need for public warning, and the extent of effectiveness checks for the recall. The FDA review and/or recommend changes to the firm's recall strategy, as appropriate. The critical recall information list includes the identity of the product; summary of the failure; amount of product produced in the distribution chain and direct account. Product recalls clashes thousands of companies every year affecting: sales, testing customer relationships and disrupting supply chains. Drug recall is incubus for pharmaceutical companies. It effects the reputation of the company. The reason for the recall can be divided into two categories: manufacturing affined and safety/efficacy affined. It is essential to follow all the guidelines related to drug development and manufacturing procedure so as to minimize drug recall. PMID:25599028

Toward a Regulatory Framework for the Waterpipe

PubMed Central

Salloum, Ramzi G.; Asfar, Taghrid

2016-01-01

Waterpipe smoking has been dramatically increasing among youth worldwide and in the United States. Despite its general association with misperceptions of reduced harm, evidence suggests this is a harmful and dependence-inducing tobacco use method that represents a threat to public health. Waterpipe products continue to be generally unregulated, which likely has contributed to their spread. The Family Smoking Prevention and Tobacco Control Act of 2009 granted the US Food and Drug Administration (FDA) the authority to regulate waterpipe products, and the FDA finalized a rule extending its authority over waterpipe products in May 2016. This critical step in addressing the alarming increase in waterpipe smoking in the United States has created urgency for research to provide the evidence needed for effective regulatory initiatives for waterpipe products. We aim to stimulate such research by providing a framework that addresses the scope of waterpipe products and their unique context and use patterns. The proposed framework identifies regulatory targets for waterpipe product components (i.e., tobacco, charcoal, and device), the waterpipe café setting, and its marketing environment dominated by Internet promotion. PMID:27552262

8th GCC: consolidated feedback to US FDA on the 2013 draft FDA guidance on bioanalytical method validation.

PubMed

Bower, Joseph; Fast, Douglas; Garofolo, Fabio; Gouty, Dominique; Hayes, Roger; Lowes, Steve; Nicholson, Robert; LeLacheur, Richard; Bravo, Jennifer; Shoup, Ronald; Dumont, Isabelle; Carbone, Mary; Zimmer, Jennifer; Ortuno, Jordi; Caturla, Maria Cruz; Datin, Jim; Lansing, Tim; Fatmi, Saadya; Struwe, Petra; Sheldon, Curtis; Islam, Rafiqul; Yu, Mathilde; Hulse, Jim; Kamerud, John; Lin, John; Doughty, John; Kurylak, Kai; Tang, Daniel; Buonarati, Mike; Blanchette, Alexandre; Levesque, Ann; Gagnon-Carignan, Sofi; Lin, Jenny; Ray, Gene; Liu, Yanseng; Khan, Masood; Xu, Allan; El-Sulayman, Gibran; DiMarco, Chantal; Bouhajib, Mohammed; Tacey, Dick; Jenkins, Rand; der Strate, Barry van; Briscoe, Chad; Karnik, Shane; Rhyne, Paul; Garofolo, Wei; Schultz, Gary; Roberts, Andrew; Redrup, Mike; DuBey, Ira; Conliffe, Phyllis; Pekol, Teri; Hantash, Jamil; Cojocaru, Laura; Allen, Mike; Reuschel, Scott; Watson, Andrea; Farrell, Colin; Groeber, Elizabeth; Malone, Michele; Nowatzke, William; Fang, Xinping

2014-01-01

The 8th GCC Closed Forum for Bioanalysis was held in Baltimore, MD, USA on 5 December 2013, immediately following the 2013 AAPS Workshop (Crystal City V): Quantitative Bioanalytical Methods Validation and Implementation--The 2013 Revised FDA Guidance. This GCC meeting was organized to discuss the contents of the draft revised FDA Guidance on bioanalytical method validation that was published in September 2013 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants, from seven countries, representing 46 bioanalytical CRO companies/sites. This event represented a unique opportunity for CRO bioanalytical experts to share their opinions and concerns regarding the draft FDA Guidance, and to build unified comments to be provided to the FDA.

Resolving Risks in Individual Astronauts: A New Paradigm for Critical Path Exposures

NASA Technical Reports Server (NTRS)

Richmond, Robert C.

2005-01-01

The limited number of astronauts available for risk-assessment prevents classic epidemiologic study, and thereby requires alternative approach to assessing risks within individual astronauts exposed to toxic agents identified within the Bioastronautics Critical Path Roadmap (BCPR). Developing a system of noninvasive real-time biodosimetry that provides large datasets for analyses before, during, and after missions for simultaneously determining 1) the kinds of toxic insult, 2) the degree of that insult, both within tissues absorbing that insult, would be usehl for resolving statistically significant risk-assessment in individual astronauts. Therefore, a currently achievable multiparametric paradigm is presented for use in analyzing gene-expression and protein-expression so as to establish predictive outcomes.

A path integral approach to the full Dicke model with dipole-dipole interaction

NASA Astrophysics Data System (ADS)

Aparicio Alcalde, M.; Stephany, J.; Svaiter, N. F.

2011-12-01

We consider the full Dicke spin-boson model composed by a single bosonic mode and an ensemble of N identical two-level atoms with different couplings for the resonant and anti-resonant interaction terms, and incorporate a dipole-dipole interaction between the atoms. Assuming that the system is in thermal equilibrium with a reservoir at temperature β-1, we compute the free energy in the thermodynamic limit N → ∞ in the saddle-point approximation to the path integral and determine the critical temperature for the super-radiant phase transition. In the zero temperature limit, we recover the critical coupling of the quantum phase transition, presented in the literature.

Some tests of wet tropospheric calibration for the CASA Uno Global Positioning System experiment

NASA Technical Reports Server (NTRS)

Dixon, T. H.; Wolf, S. Kornreich

1990-01-01

Wet tropospheric path delay can be a major error source for Global Positioning System (GPS) geodetic experiments. Strategies for minimizing this error are investigted using data from CASA Uno, the first major GPS experiment in Central and South America, where wet path delays may be both high and variable. Wet path delay calibration using water vapor radiometers (WVRs) and residual delay estimation is compared with strategies where the entire wet path delay is estimated stochastically without prior calibration, using data from a 270-km test baseline in Costa Rica. Both approaches yield centimeter-level baseline repeatability and similar tropospheric estimates, suggesting that WVR calibration is not critical for obtaining high precision results with GPS in the CASA region.

On the Distribution of Free Path Lengthsfor the Periodic Lorentz Gas

NASA Astrophysics Data System (ADS)

Bourgain, Jean; Golse, François; Wennberg, Bernt

Consider the domain and let the free path length be defined as The distribution of values of is studied in the limit as for all . It is shown that the value is critical for this problem: in other words, the limiting behavior of depends only on whether γ is larger or smaller than .

21 CFR 1.279 - When must prior notice be submitted to FDA?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false When must prior notice be submitted to FDA? 1.279... Imported Food § 1.279 When must prior notice be submitted to FDA? (a) Except as provided in paragraph (c) of this section, you must submit the prior notice to FDA and the prior notice submission must be...

21 CFR 1.279 - When must prior notice be submitted to FDA?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false When must prior notice be submitted to FDA? 1.279... Imported Food § 1.279 When must prior notice be submitted to FDA? (a) Except as provided in paragraph (c) of this section, you must submit the prior notice to FDA and the prior notice submission must be...

21 CFR 1.279 - When must prior notice be submitted to FDA?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false When must prior notice be submitted to FDA? 1.279... Imported Food § 1.279 When must prior notice be submitted to FDA? (a) Except as provided in paragraph (c) of this section, you must submit the prior notice to FDA and the prior notice submission must be...

21 CFR 1.279 - When must prior notice be submitted to FDA?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false When must prior notice be submitted to FDA? 1.279... Imported Food § 1.279 When must prior notice be submitted to FDA? (a) Except as provided in paragraph (c) of this section, you must submit the prior notice to FDA and the prior notice submission must be...

21 CFR 1.279 - When must prior notice be submitted to FDA?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false When must prior notice be submitted to FDA? 1.279... Imported Food § 1.279 When must prior notice be submitted to FDA? (a) Except as provided in paragraph (c) of this section, you must submit the prior notice to FDA and the prior notice submission must be...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening test for HBsAg); and (4) Hepatitis C (e.g., FDA licensed screening test for anti-HCV). (b) In the case... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

Adherence of Pharmaceutical Advertisements in Medical Journals to FDA Guidelines and Content for Safe Prescribing

PubMed Central

Korenstein, Deborah; Keyhani, Salomeh; Mendelson, Ali; Ross, Joseph S.

2011-01-01

Background Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA); adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing. Methods and Findings Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1–14). Six “teaser” advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA-described bias, and 27 (32.5%) were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence. Conclusions Few physician-directed print pharmaceutical advertisements adhere to all FDA guidelines; over half fail to quantify serious risks. The FDA could better protect public health by creating new more objective advertisement guidelines requiring transparent presentation of basic safety and efficacy information. PMID:21858076

Adherence of pharmaceutical advertisements in medical journals to FDA guidelines and content for safe prescribing.

PubMed

Korenstein, Deborah; Keyhani, Salomeh; Mendelson, Ali; Ross, Joseph S

2011-01-01

Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA); adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing. Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1-14). Six "teaser" advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA-described bias, and 27 (32.5%) were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence. Few physician-directed print pharmaceutical advertisements adhere to all FDA guidelines; over half fail to quantify serious risks. The FDA could better protect public health by creating new more objective advertisement guidelines requiring transparent presentation of basic safety and efficacy information.

FDA 101: Regulating Biological Products

MedlinePlus

... Home For Consumers Consumer Updates FDA 101: Regulating Biological Products Share Tweet Linkedin Pin it More sharing ... about this diverse and highly important field. What biological products does FDA regulate? The Center for Biologics ...

Frequency and level of evidence used in recommendations by the National Comprehensive Cancer Network guidelines beyond approvals of the US Food and Drug Administration: retrospective observational study.

PubMed

Wagner, Jeffrey; Marquart, John; Ruby, Julia; Lammers, Austin; Mailankody, Sham; Kaestner, Victoria; Prasad, Vinay

2018-03-07

To determine the differences between recommendations by the National Comprehensive Cancer Network (NCNN) guidelines and Food and Drug Administration approvals of anticancer drugs, and the evidence cited by the NCCN to justify recommendations where differences exist. Retrospective observational study. National Comprehensive Cancer Network and FDA. 47 new molecular entities approved by the FDA between 2011 and 2015. Comparison of all FDA approved indications (new and supplemental) with all NCCN recommendations as of 25 March 2016. When the NCCN made recommendations beyond the FDA's approvals, the recommendation was classified and the cited evidence noted. 47 drugs initially approved by the FDA between 2011 and 2015 for adult hematologic or solid cancers were examined. These 47 drugs were authorized for 69 FDA approved indications, whereas the NCCN recommended these drugs for 113 indications, of which 69 (62%) overlapped with the 69 FDA approved indications and 44 (39%) were additional recommendations. The average number of recommendations beyond the FDA approved indications was 0.92. 23% (n=10) of the additional recommendations were based on evidence from randomized controlled trials, and 16% (n=7) were based on evidence from phase III studies. During 21 months of follow-up, the FDA granted approval to 14% (n=6) of the additional recommendations. The NCCN frequently recommends beyond the FDA approved indications even for newer, branded drugs. The strength of the evidence cited by the NCCN supporting such recommendations is weak. Our findings raise concern that the NCCN justifies the coverage of costly, toxic cancer drugs based on weak evidence. 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.

How drugs are developed and approved by the FDA: current process and future directions.

PubMed

Ciociola, Arthur A; Cohen, Lawrence B; Kulkarni, Prasad

2014-05-01

This article provides an overview of FDA's regulatory processes for drug development and approval, and the estimated costs associated with the development of a drug, and also examines the issues and challenges facing the FDA in the near future. A literature search was performed using MEDLINE to summarize the current FDA drug approval processes and future directions. MEDLINE was further utilized to search for all cost analysis studies performed to evaluate the pharmaceutical industry R&D productivity and drug development cost estimates. While the drug approval process remains at high risk and spans over multiple years, the FDA drug review and approval process has improved, with the median approval time for new molecular drugs been reduced from 19 months to 10 months. The overall cost to development of a drug remains quite high and has been estimated to range from $868M to $1,241M USD. Several new laws have been enacted, including the FDA Safety and Innovation Act (FDASIA) of 2013, which is designed to improve the drug approval process and enhance access to new medicines. The FDA's improved processes for drug approval and post-market surveillance have achieved the goal of providing patients with timely access to effective drugs while minimizing the risk of drug-related harm. The FDA drug approval process is not without controversy, as a number of well-known gastroenterology drugs have been withdrawn from the US market over the past few years. With the approval of the new FDASIA law, the FDA will continue to improve their processes and, working together with the ACG through the FDA-Related Matters Committee, continue to develop safe and effective drugs for our patients.

21 CFR 814.84 - Reports.

Code of Federal Regulations, 2011 CFR

2011-04-01

... be reported to FDA under § 814.39(b). (2) Contain a summary and bibliography of the following... bibliography, FDA concludes that the agency needs a copy of the unpublished or published reports, FDA will...

36 CFR 13.976 - Fire.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (fda) § 13.976 Fire. Lighting or maintaining a fire is prohibited in the FDA except— (a) In established receptacles within designated campgrounds; (b) From October 1 through April 14 in that portion of the FDA...

36 CFR 13.976 - Fire.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (fda) § 13.976 Fire. Lighting or maintaining a fire is prohibited in the FDA except— (a) In established receptacles within designated campgrounds; (b) From October 1 through April 14 in that portion of the FDA...

36 CFR 13.976 - Fire.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (fda) § 13.976 Fire. Lighting or maintaining a fire is prohibited in the FDA except— (a) In established receptacles within designated campgrounds; (b) From October 1 through April 14 in that portion of the FDA...

AMCP Partnership Forum: Enabling the Exchange of Clinical and Economic Information Pre-FDA Approval.

PubMed

2017-01-01

Current federal laws and FDA regulations have significantly restricted the sharing of clinical and health economic information on biopharmaceuticals that have yet to receive FDA approval. Over the past several years, organizations that make health care coverage decisions, including those that set copayments, premiums, and formulary placement, have expressed a need for receiving this information before approval, as long as appropriate safeguards exist to prevent this information from reaching unintended entities. Population health decision makers have indicated that waiting until FDA approval is often too late for the critical planning, budgeting, and forecasting associated with health benefit design, especially given the recent influx of high-cost medications and scrutiny for better evaluation and preparation. Recognizing that securities laws restrict the disclosure of nonpublic information and may need to be amended, permissible early dissemination would allow population health decision makers to incorporate clinical and economic information for pipeline drugs or expanded indications into financial forecasting for the following year's plan. Access to this information is needed 12-18 months before FDA approval when organizations are deciding on terms of coverage and budgetary assumptions for state health insurance rate filings, Medicare and Medicaid bids, contracts with health care purchasers, and other financial arrangements. The need for exchange of clinical economic information before FDA approval was first introduced at a previous Academy of Managed Care (AMCP) forum in March 2016, which addressed section 114 of the Food and Drug Administration Modernization Act and the communication of such information after FDA approval. To address preapproval information specifically, AMCP convened a Partnership Forum on September 13-14, 2016. This forum included a diverse group of stakeholders representing managed care, the biopharmaceutical industry, providers, patients, health economists, academia, and others. The multistakeholder group represented the key professionals and entities affected by the federal laws and FDA regulations that restrict the sharing of preapproval information and the collective credibility necessary for proposing this new communication process. Forum participants primarily focused on 6 items of discussion: (1) creating and defining new terms for how biopharmaceutical manufacturers may provide clinical and economic information 12-18 months before FDA approval; (2) defining the clinical and scientific standards that this information should meet; (3) determining which entities should have access to this information and the value to each; (4) the format and process by which this information should be disseminated; (5) developing definitions for existing terms referenced in current laws, regulations, or guidance documents that would need to be modernized to align with the identified new term; and (6) providing safeguards to prevent this information from reaching unintended entities. Forum participants selected "preapproval information exchange" (PIE) as the correct term to describe this proposed new communication process and to be inclusive of data from pivotal phase III clinical trials, pharmaco-economic data, and patient-reported outcomes, as well as other relevant items, including anticipated indications, place in therapy, and routes of administration. Stakeholders agreed that PIE should be truthful, non-misleading, and include a broad range of information to meet the needs of population health decision makers and health care technology evolution. Recipients of PIE would be limited to population health decision makers who need this information for coverage decisions. The format and process for PIE disseminated should allow for a bidirectional exchange between manufacturers and population health decision makers but should not be proscribed in legislation. Furthermore, new legislative language may be beneficial, since PIE is a novel category of information. New legislation could provide a safe harbor and clarity that PIE does not violate preapproval promotion and the Federal Food, Drug, and Cosmetic Act and its regulations. The AMCP Partnership Forum on Enabling the Exchange of Clinical and Economic Data Pre-FDA Approval and the development of this proceedings document were supported by AbbVie, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Celgene, Intarcia Therapeutics, Eli Lilly and Company, GlaxoSmithKline, Merck, National Pharmaceutical Council, Novo Nordisk, Pfizer, Pharmaceutical Research and Manufacturers of America, Precision for Value, Sanofi, Takeda Pharmaceuticals, U.S.A., and Xcenda. All sponsors participated in the forum and in revising and approving the manuscript.

Factors Influencing the Decision to Proceed to Firmware Upgrades to Implanted Pacemakers for Cybersecurity Risk Mitigation.

PubMed

Saxon, Leslie A; Varma, Niraj; Epstein, Laurence M; Ganz, Leonard I; Epstein, Andrew E

2018-05-10

In August 2017, the first major recall for cybersecurity vulnerabilities in pacemakers capable of remote connectivity was released that impacted 465,000 United States patients. 1,2 The FDA approved a firmware update designed by the manufacturer of the devices as a remediation (Abbott , formally St. Jude Medical). The recall was in response to the public disclosure of vulnerability by an investment firm and produced in a lab environment that could allow an unauthorized party in close proximity to a patient to impact the performance of the device or modify device settings via radio frequency communication. 3 While an exploit has not occurred in a patient and requires a high degree of resources and skill to execute, if accomplished, it could pose a significant risk to device safety and essential performance and cause patient harm. The FDA defines this as an uncontrolled vulnerability. 2 The recall recommendations were coordinated between the FDA, the Industrial Control Systems Cyber Emergency Response Team (ICS-CERT), a division of Homeland Security that responds to and coordinates disclosure of critical infrastructure cybersecurity vulnerabilities and Abbott. 1 All parties urged caution and shared decision making between patient and clinician as to whether to have the device firmware update, a process that requires a clinic visit to implement with a device programmer. The manufacturer bench tested the firmware update but the only prior experience with an implanted device firmware updates was a 2012 ICD firmware update that demonstrated a 0.197% risk of device back-up mode pacing after the upgrade was performed.

The “Natural” vs. “Natural Flavors” Conflict in Food Labeling: A Regulatory Viewpoint.

PubMed

Goodman, Matthew J

Food branded with a Natural label can be found in any grocery store across the United States. Consumers consider this label to be an important attribute when making a purchasing decision and billions of dollars are spent annually on these products. While many consumers believe Natural foods are healthier, heavy reliance on that assumption is misguided as “Natural” has no formal legal definition—it’s merely defined pursuant to an FDA approved informal policy. Another important health attribute in a consumer’s purchasing decision is the presence of natural flavors in food. However, unlike the term Natural, FDA has promulgated legally binding regulations for natural flavors. These flavors are currently the fourth most common food ingredient listed on food labels. In reality, “natural flavors” are a far cry from what consumers might expect, as they can contain both artificial and synthetic chemicals (often used as processing aids). Nonetheless, without a legally binding Natural regulation, there has been little opportunity to contest the naturalness of natural flavors in the past. Recently, FDA has initiated a notification of request for comments on use of the term Natural, so an attempt to promulgate regulations may be underway. Thus, it is appropriate to consider where natural flavors will fall if binding regulations are set forth. This article looks at the Natural debate, its history, and model regulatory standards worth considering. Within that context, it also provides a critical discussion concerning a misunderstood, yet federally regulated, ingredient that our society so heavily consumes: natural flavors.

New Criteria for Assessing the Accuracy of Blood Glucose Monitors Meeting, October 28, 2011

PubMed Central

Walsh, John; Roberts, Ruth; Vigersky, Robert A.; Schwartz, Frank

2012-01-01

Glucose meters (GMs) are routinely used for self-monitoring of blood glucose by patients and for point-of-care glucose monitoring by health care providers in outpatient and inpatient settings. Although widely assumed to be accurate, numerous reports of inaccuracies with resulting morbidity and mortality have been noted. Insulin dosing errors based on inaccurate GMs are most critical. On October 28, 2011, the Diabetes Technology Society invited 45 diabetes technology clinicians who were attending the 2011 Diabetes Technology Meeting to participate in a closed-door meeting entitled New Criteria for Assessing the Accuracy of Blood Glucose Monitors. This report reflects the opinions of most of the attendees of that meeting. The Food and Drug Administration (FDA), the public, and several medical societies are currently in dialogue to establish a new standard for GM accuracy. This update to the FDA standard is driven by improved meter accuracy, technological advances (pumps, bolus calculators, continuous glucose monitors, and insulin pens), reports of hospital and outpatient deaths, consumer complaints about inaccuracy, and research studies showing that several approved GMs failed to meet FDA or International Organization for Standardization standards in post-approval testing. These circumstances mandate a set of new GM standards that appropriately match the GMs’ analytical accuracy to the clinical accuracy required for their intended use, as well as ensuring their ongoing accuracy following approval. The attendees of the New Criteria for Assessing the Accuracy of Blood Glucose Monitors meeting proposed a graduated standard and other methods to improve GM performance, which are discussed in this meeting report. PMID:22538160

Biotechnology stock prices before public announcements: evidence of insider trading?

PubMed

Overgaard, C B; van den Broek, R A; Kim, J H; Detsky, A S

2000-03-01

Unique financial challenges faced by biotechnology companies developing therapeutics have contributed to the creation of a highly sensitive market, where stock prices are capable of great fluctuation. The potential for significant financial reward and the nature of the scientific review process make this industry susceptible to illegal share trading on nonpublic information. We examined stock prices of biotechnology products before and after announcement of Phase III clinical trial and Food and Drug Administration (FDA) Advisory Panel results for indirect evidence of insider trading. Biotechnology stock prices were recorded for 98 products undergoing Phase III clinical trials and 49 products undergoing FDA Advisory Panel review between 1990 and 1998. Prices were recorded for 120 consecutive trading days before and after public announcement of these two events. We compared the average change in stock price of successful products ('winners') with unsuccessful products ('losers') before the public announcement of results for both critical events. The difference between average stock price change from 120 to 3 days before public announcement of results of Phase III clinical trial winners (+27%) and losers (-4%) was highly significant (P = 0.0007). A similar but non-significant difference was observed between the average stock price of winning (+27%) and losing products (+13%) before FDA Advisory Panel review announcements (P = 0.25). Our results provide indirect evidence that insider trading may be common in the biotechnology industry. Clinical investigators may wish to consider this issue before participating in any equity position in the biotechnology industry, especially if they are going to perform research for those companies.