DIA's Content Currents provides you with new and important global regulatory developments and their impact on pharmaceutical, biotechnology, and medical product development.
EDITION PUBLISHED: July 25, 2014
SECTION 1 FDA GUIDANCES & MAPPS
CDER List of Guidance Documents
CDER Guidances: New/Revised/Withdrawn through 6/30/14
The links above lead to the List of Guidance Documents (CDER) updated on July 7, 2014, and to CDER Guidances that are new, revised, or withdrawn through the second calendar quarter of 2014.
Guidance Agenda: Guidance Documents CBER is Planning to Publish During Calendar Year 2014 (PDF - 31KB)
CDRH FY 2014 Proposed Guidance Development
On July 23, 2014, FDA announced the availability of a draft and revised draft guidances entitled “Bioequivalence Recommendations for Specific Products.” The recommendations provide product-specific guidance on the design of BE studies to support abbreviated new drug applications (ANDAs). Comments should be submitted by September 22, 2014, to assure consideration before work on the final guidance begins. [Federal Register]
On July 25, 2014, FDA announced the availability of a revised draft guidance entitled “Providing Regulatory Submissions in Electronic Format—Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications.” This draft guidance outlines Electronic Common Technical Document (eCTD) specification requirements for certain submissions to new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), and investigational new drug applications (INDs) and is being issued for public comment. This draft guidance revises and replaces a previous draft guidance entitled ‘‘Providing Regulatory Submissions in Electronic Format—Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications’’ that was issued in January 2013 (2013 draft guidance on eCTD Specifications). Comments should be submitted by September 21, 2014 to assure consideration before work on the final document begins. [Federal Register]
SECTION 2 FDA NOTES & RELATED NEWS
Dr. Frances Kelsey, Who Protected Americans from Thalidomide, Turns 100
July 24 marks the 100th birthday of one of America’s most celebrated public servants, Frances Oldham Kelsey, Ph.D., M.D. She was on the faculty of the University of South Dakota and practicing medicine when, in 1960, she accepted the offer to become a medical officer at FDA.
A month after assuming her position she was assigned the review of a new drug application for thalidomide, a sedative that had been used by expectant mothers and many others in dozens of countries since the late 1950s. U.S. law at the time required a firm to provide evidence of a drug’s safety as a requirement for sale. Despite the global popularity of this drug, and despite a constant and increasing pressure from the firm to approve the application, Dr. Kelsey refused to do that without adequate evidence that the drug was safe, a decision that was supported by her colleagues and superiors.
Thanks to Dr. Kelsey’s “exceptional judgment in evaluating a new drug” — as her firm stand was described in the President’s Award for Distinguished Federal Civilian Service she received from President John Kennedy — the U.S. was mostly spared the tragedies. But the close encounter with a public health catastrophe convinced Congress and the White House to resuscitate proposals to revitalize the regulation of pharmaceuticals. The result was the 1962 enactment of the Kefauver-Harris Drug Amendments that mandated “substantial evidence” of a drug’s effectiveness as developed by “experts qualified by scientific training,” in addition to evidence of a drug’s safety, and provided for greater oversight of drug investigations. More at link above. (FDA.gov)
FDA Posts National Medical Device Curriculum
The National Medical Device Curriculum is a series of fictional case studies designed to help academic institutions and science and technology innovators understand FDA’s medical device regulatory processes. The FDA believes that better understanding of regulatory processes will accelerate the delivery of innovative medical devices to patients.
The National Medical Device Curriculum provides students with FDA-endorsed core knowledge on how to design, test and clinically evaluate devices, identify the root causes of adverse events and device malfunctions, develop iterative device designs, and navigate the regulatory process.
Designed as a series of fictional case studies based on real-world medical device scenarios, the curriculum follows a format similar to Harvard Business Review Case Studies. More at link above. (FDA.gov)
Transcript Posted for "Proposed Risk-Based Regulatory Framework and Strategy for Health Information Technology" Workshop
The FDA, Office of the National Coordinator for Health Information Technology (ONC), and Federal Communication Commission (FCC) conducted a public workshop entitled “Proposed Risk-Based Regulatory and Framework and Strategy for Health Information Technology” on May 13-15, 2014.
The FDA, ONC, and FCC sought broad input from stakeholders and experts. The topic discussed was the FDASIA health IT report that contained a proposed strategy and recommendations on an appropriate, risk-based regulatory framework for health IT that promotes innovation, protects patient safety, and avoids regulatory duplication.
The transcript for this workshop has now been posted on the FDA website. More at link above. (FDA.gov)
Filing of First Biosimilar Offers a Glimpse of Possible Savings for the US
The FDA application filed Thursday by Sandoz for a biosimilar drug is just the beginning in realizing the huge savings that biosimilars can bring to the U.S. compared with expensive biologics, Jason Millman writes. The local biosimilar market's development will be key amid payers' concerns about a projected increase in the country's drug spending over the next few years, Millman writes. (Washington Post via FDLI SmartBrief)
FDA Announces New Leadership for Office of Generic Drugs Super-Office
The US Food and Drug Administration's (FDA) long-awaited reorganization of its Office of Generic Drugs (OGD) is finally getting underway, the agency said in a statement this past Monday (July 21). Since late 2012, FDA has been planning to elevate OGD to a so-called "Super Office"—an office which reports directly to the director of the Center for Drug Evaluation and Research, a position now held by longtime Director Janet Woodcock.
Though the agency experienced some delays in implementing its plan, it released a December 2013 notice indicating that the plan had been approved, and that four offices would be created within OGD: the Office of Research and Standards, the Office of Bioequivalence, the Office of Generic Drug Policy, and the Office of Regulatory Operations.
In Monday’s update, FDA has announced that it has filled all four of those offices with new leaders:
- Rob Lionberger, now acting deputy director for science, will lead the Office of Research and Standards (ORS), which includes the Division of Therapeutic Performance and the Division of Quantitative Methods and Modeling.
- John Peters, now a supervisory medical officer, will lead the Office of Bioequivalence (OB), which includes the three Divisions of Bioequivalence and the Division of Clinical Review.
- Jason Woo, now the implementation manager for the Generic Drug User Fee Act (GDUFA), will lead the Office of Regulatory Operations (ORO), which includes the Division of Filing Review, the Division of Labeling Review, the Division of Project Management, and the Division of Quality Management Systems.
- Keith Flanagan, regulatory counsel at OGD, will remain as transition lead for the Office of Generic Drug Policy (OGDP), which includes the Division of Policy Development and the Division of Legal and Regulatory Support.
More at link above. (Regulatory Focus)
SECTION 3 AGENCY AND ADVISORY COMMITTEE MEETINGS
Patient-Focused Drug Development: Disease Area Meetings Planned for FY2013-2015
Public Hearing. Confidentiality of Interim Results in Cardiovascular (CV) Outcomes Safety Trials. August 11, 2014. White Oak Campus, Silver Spring, MD. The agency is seeking stakeholder input on the potential effects of disclosing information or analyses from ongoing CV outcomes trials, including what interim data "represent the greatest risk to trial integrity or jeopardize trial continuation." [FDA.gov]
Public Meeting. Scientific Meeting of the National Antimicrobial Resistance Monitoring System. August 12-13, 2014. White Oak Campus, Silver Spring, MD. The purpose of the meeting is to discuss progress made in achieving the goals of the National Antimicrobial Resistance Monitoring System (NARMS) Strategic Plan: 2012–2016. [Federal Register]
Public Workshop. Hemostatic Medical Devices for Trauma Use. September 3-4, 2014. White Oak Campus, Silver Spring, MD. The purpose of this workshop is to discuss factors that contribute to hemostatic medical device performance and reliability and types of studies used to assess bleeding and validate methods to evaluate the severity of bleeding, and to define regulatory pathways for novel products. [Federal Register]
New: Public Meeting. Advancing the Use of Biomarkers and Pharmacogenomics. September 5, 2014. Washington, DC. The purpose of the public meeting is to initiate constructive discussion and information sharing on the advancement of biomarker science in the context of therapeutic product development among relevant stakeholders. [Federal Register]
Public Meeting in Collaboration with the National Cancer Institute. Methodological Considerations in Evaluation of Cancer as an Adverse Outcome Associated with Use of non-Oncological Drugs and Biological Products in the Post-approval Setting. September 10 - 11, 2014. Silver Spring, MD. The purpose of the public meeting is to engage in constructive dialogue and information sharing among regulators, researchers, the pharmaceutical industry, public health agencies, health care providers, and the general public concerning challenges in designing and implementing post-approval studies to evaluate the risk of cancer associated with use of non-oncological drugs and biological products. The input from this meeting and public docket will be used to inform the Agency on best study design and methodological options to consider when evaluating cancer risk in the post-approval setting. [Federal Register]
Public Advisory Committee Meeting. Cardiovascular and Renal Drugs Advisory Committee. September 10, 2014. White Oak Campus, Silver Spring, MD. The committee will be asked to discuss the potential clinical utility of fixed-combination prescription drugs composed of an anti-hypertensive drug, aspirin, and a statin administered to reduce the risk of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke in patients with a history of cardiovascular disease. The committee will be asked to discuss the patient population that could benefit from such a product, whether that population would be likely to take such a drug long term, and how this could be assured. [Federal Register]
Meeting. Third Annual Patient Network Meeting; Under the Microscope: Pediatric Drug Development. September 10, 2014. Washington, DC. The meeting will serve as a forum for FDA’s stakeholders (patients, caregivers, patient advocates, healthcare professional groups, the general public, academia, and industry) to learn about regulations that encourage pediatric product development; to discuss ways to advance pediatric product development, how health disparities impact pediatric product development, the importance of transparency in pediatric clinical trials, and how analysis of information from failed pediatric clinical trials might improve future designs for pediatric trials; and to identify ways patient input can benefit clinical trial design for pediatric trials. [Federal Register]
Meeting. International Medical Device Regulators Forum (IMDRF), September 15-19, 2014. Embassy Row Hilton, Washington, DC. A week of global meetings to discuss worldwide medical device regulation and harmonization efforts. [FDA.gov]
Public Advisory Committee Meeting. Joint Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. September 17, 2014. Hyattsville, MD. The committees will discuss the appropriate indicated population for testosterone replacement therapy and the potential for adverse cardiovascular outcomes associated with this use. [Federal Register]
Public Workshop. Pediatric Clinical Investigator Training Workshop. September 22, 2014. Bethesda, MD. The purpose of this workshop is to provide investigators with training and expertise in designing and conducting clinical trials in pediatric patients that will lead to appropriate labeling. [Federal Register]
Public Meeting. Patient-Focused Drug Development for Hemophilia A, Hemophilia B, von Willebrand Disease, and Other Heritable Bleeding Disorders. September 22, 2014. White Oak Campus, Silver Spring, MD. The public meeting is intended to allow FDA to obtain patient perspectives on the impact of Hemophilia A, Hemophilia B, von Willebrand Disease, and other heritable bleeding disorders on daily life as well as patient perspectives on the available therapies for these disorders. [Federal Register]
Public Workshop. Next-Generation Sequencing Technology, Data Formats Standardization and Promotion of Interoperability Protocols. September 24-25, 2014. National Institute of Health Campus, Bethesda, MD. The purpose of the workshop is to engage NGS stakeholders in a forum to discuss the current use of the technology and the development of data standards of NGS-related information. [Federal Register]
Public Meeting. Patient-Focused Drug Development for Idiopathic Pulmonary Fibrosis. September 26, 2014. White Oak Campus, Silver Spring, MD. The public meeting is intended to allow FDA to obtain patient perspectives on the impact of idiopathic pulmonary fibrosis on daily life as well as patient views on treatment approaches for idiopathic pulmonary fibrosis. [Federal Register]
Public Workshop. Additive Manufacturing of Medical Devices: An Interactive Discussion on the Technical Considerations of 3–D Printing. October 8-9, 2014. White Oak Campus, Silver Spring, MD. The purpose of this workshop is to provide a forum for FDA, medical device manufactures, additive manufacturing companies, and academia to discuss technical challenges and solutions of 3–D printing. The Agency would like input regarding technical assessments that should be considered for additively manufactured devices to provide a transparent evaluation process for future submissions. [Federal Register]
New: Clinical Investigator Training Course. November 4-6, 2014. College Park, MD. This training course, a co-sponsored event of FDA CDER and Duke University Office of Continuing Medical Education, is intended to provide clinical investigators with expertise in the design, conduct, and analysis of clinical trials; improve the quality of clinical trials; and enhance the safety of trial participants. [Federal Register]
SECTION 4 OTHER REGULATORY AUTHORITIES & ORGANIZATIONS
American Society for Microbiology: Statement on Recent Biosafety Lapses
The recent events at the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH), which are documented in the report below, reveal significant lapses in biosafety, biosecurity, oversight and compliance with the Select Agents and Toxins regulations. At every level, in teaching, research, and diagnostic laboratories, microbiologists must take all steps possible to guarantee biosafety, to protect themselves, their co-workers, and the broader public from microorganisms that can cause disease. Microbiologists who work with dangerous pathogens have a responsibility to understand and comply with biosafety and biosecurity regulations. As such, ASM members must ensure that they are acting with the highest level of responsibility and accountability in their laboratories.” More at link above. (ASM via MedPage Today)
HHS issues interpretative rule on 340B and Orphan drugs
As expected, HHS's Health Resources and Services Administration (HRSA) issued an interpretative rule on Monday that states that Orphan drugs can be discounted under Medicare's 340B program when used for non-Orphan indications. The 340B program requires manufacturers to deeply discount outpatient drugs to hospitals and clinics bearing the brunt of healthcare for low income and other special populations. In 2010, Congress amended the program to exclude Orphan drugs from discounting, but the law was unclear on whether the exclusion applied when the drugs were used for non-Orphan indications. More at link above. (BioCentury)
GAO Issues Call for Nominations to Fill PCORI Board Vacancy
The U.S. Government Accountability Office (GAO) has issued a call for nominations to fill a seat on the Patient-Centered Outcomes Research Institute (PCORI) Board of Governors recently vacated by Arnold Epstein, MD.
The Patient Protection and Affordable Care Act, which authorized PCORI’s establishment, assigns the Comptroller General of the United States responsibility for appointing the members of PCORI’s Board. Under the legislation, Board members represent a wide range of healthcare stakeholders, including patients and healthcare consumers. GAO’s call for nominations focuses specifically on candidates who can bring the perspectives of quality improvement or health services researchers, the area that Epstein represented. More at link above. (PCORI.org)
Partnering with Patients to Drive Shared Decisions, Better Value, and Care Improvement: Workshop Proceedings
The Institute of Medicine's Roundtable on Value & Science-Driven Health Care held a workshop, titled Partnering with Patients to Drive Shared Decisions, Better Value, and Care Improvement, on February 25 and 26, 2013. The workshop focused on identifying and exploring issues, attitudes, and approaches to increasing patient engagement in and demand for the following: shared decision making and better communication about the evidence in support of testing and treatment options; the best value from the health care they receive; and the use of data generated in the course of their care experience for care improvement.
The proceedings from the workshop are now available at the link above. (IOM)
NIH programs to focus on emerging areas of science
Scientific areas ripe for targeted investments in technology development and research to improve health are the focus of new programs of the National Institutes of Health’s Common Fund. Common Fund programs are designed to pursue major opportunities and gaps in biomedical research that no single NIH Institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research.
The new programs include work to facilitate the study of how sugar modifications affect proteins (the Glycoscience program), to understand the arrangement of DNA within cells in four dimensions (the 4D Nucleome program), and to enable the development of new therapies that allow control of organ function through manipulation of nerves (the Stimulating Peripheral Activity to Relieve Conditions (SPARC) program). NIH believes that each new program has the ability to catalyze biomedical advances and expand research in critical areas of human health. More at link above. (NIH.gov)
Harvard Medical School and the Phelan-McDermid Syndrome Foundation Contract Leverages the tranSMART Open-Source Knowledge Management Platform
The Phelan-McDermid Syndrome Foundation and the Center of Biomedical Informatics at Harvard Medical School were awarded a nearly $1 million contract from the Patient-Centered Outcomes Research Institute (PCORI) to undertake an exciting research endeavor that will leverage the tranSMART platform, a global, open-source knowledge management platform for scientists to share pre-competitive translational research data.
The team will collect and integrate previously-siloed medical and research data to advance knowledge and expedite research inquiries for families affected by Phelan-McDermid Syndrome (PMS), a very rare genetic condition with a moderate to severe impact on brain development and strong association with autism spectrum disorders.
Using tranSMART, the Natural Language Processing tool cTAKES and the i2b2 (Informatics for Integrating Biology and the Bedside) data model, the PMS data network will provide an informatics backbone, helping researchers to mine diverse data sets and make and share meaningful insights with the PCORnet research partners. "Using the functionality of i2b2 features in tranSMART, we are able to integrate patient and family-reported outcomes from the Phelan-McDermid Syndrome International Registry and electronic health records to help us effectively mine data and better understand PMS," said Dr. Paul Avillach, co_PI of the project. More at link above. (MarketWatch)
FTC commissioner warns on mobile health-data gathering
Federal Trade Commissioner Julie Brill, speaking in Washington on Wednesday, expressed concern about the way apps on smartphones and mobile devices are siphoning sensitive health data, and how some of that information may then be shared with third parties.
Brill's comments followed a May report in which the FTC revealed the results of a study of mobile health-app developers, which found that a good portion collect consumer health data and give it to third-party entities. "We don't know where that information ultimately goes," Brill told the panel. "It makes consumers uncomfortable." She has put pressure on Congress to pass laws prohibiting the collection of personal information under false pretenses.
The debate around the gathering of consumer data is intensifying as Silicon Valley tech companies take a more active interest in mobile health. Some advocacy groups, like the Association for Competitive Technology, which represents application developers, fear that innovation could be stunted if information collection were curtailed. More at link above. (Reuters)
GPhA Report: REMS Manipulated by Brand Name Companies to Impede Generic Competition
"Risk evaluation and mitigation strategies" (REMS) that ensure prescription medicines are not misused have been manipulated by brand-name drug companies to fight off generic competitors, costing consumers billions of dollars, according to a report released on Wednesday.
A report from the Generic Pharmaceutical Association said REMS have been used to prevent generic drugmakers from getting branded medicine to test their own versions, which is required to win FDA approval. This has delayed the arrival of 40 potential generic drugs, costing consumers some $5.4 billion a year, according to the report by Matrix Global Advisors and released by the generic drug trade group.
Senator Richard Blumenthal (D-Connecticut) and the US Federal Trade Commission have voiced concern over the issue. More at link above. (Reuters)
MRC gains access to more deprioritized compounds
Seven companies committed to providing access to deprioritized compounds to the U.K.'s Medical Research Council for academic research projects. The council plans to publish a full list of the available compounds this year, and U.K. scientists will be able to apply for MRC funding to conduct their projects. The companies are AstraZeneca plc; GlaxoSmithKline plc; Eli Lilly and Co.; the Janssen Research & Development LLC unit of Johnson & Johnson; Pfizer Inc; Takeda Pharmaceutical Co. Ltd.; and UCB Group.
Earlier this year, AZ partnered with MRC to evaluate over 2 million AstraZeneca molecules under a five-year deal under which the council is funding up to 15 screening projects per year across a range of therapy areas and diseases. More at link above. (BioCentury)
European Medicines Agency launches public consultation on rules of procedures for public hearings
The European Medicines Agency (EMA) has today launched a public consultation on draft rules of procedures for public hearings held by its Pharmacovigilance Risk Assessment Committee (PRAC). The rules of procedures describe the process and practical arrangements for the preparation, conduct and follow-up of public hearings.
Citizens are invited to review the proposed draft rules and send their comments to the Agency by 15 October 2014. Comments should be sent to firstname.lastname@example.org using the comments submission form.
Public hearings are a new tool for the EMA to engage European Union (EU) citizens in the regulatory process of the supervision of medicines and to listen to their views and experiences. The pharmacovigilance legislation has given the PRAC the possibility to hold public hearings as part of certain safety reviews of medicines, particularly in relation to their therapeutic effects and therapeutic alternatives available, as well as the feasibility and acceptability of proposed risk management and minimisation activities. More at link above. (EMA.eu)
India Wants Price Controls on Cancer Generics
India's National Pharmaceutical Pricing Authority (NPPA) requested pricing information on generic cancer drugs from six pharma companies so the agency can fix the products' ceiling prices.
Earlier this month, NPPA capped the prices of 50 cardiovascular and diabetes drugs, including some not listed on the essential medicines list. Under India's Drug Price Control Order, the government can fix the ceiling price or retail price of any drug in "extraordinary circumstances" if it considers the action necessary in the public interest. More at link above. (BioCentury)
Maharashtra FDA: Bring medical devices under DPCO to curb profiteering
Maharashtra Food and Drug Administration (FDA) has recommended to the Drug Controller General of India (DCGI) and National Pharmaceutical Pricing Authority (NPPA) to bring medical devices including drug eluting stents (DES) under the Drug Price Control Order (DPCO) 2013 to make them affordable to the patients.
Medical devices including drug eluting stents (DES) are classified as drugs under the Drugs and Cosmetics Act, 1940 but are not included under the DPCO. Therefore, the prices of medical devices cannot be monitored and controlled as of today. More at link above. (Pharmabiz)
SECTION 5 SOURCES REVIEWED FOR THIS NEWSLETTER
Stakeholders ask Congress for more transparency in patient data
Stakeholders requested that FDA allow pharmaceutical companies to share more information with physicians about real-world drug usage so they can make more informed choices to provide better patient care. During a Tuesday hearing held as part of the U.S. House of Representatives Energy and Commerce Committee's Path to 21st Century Cures initiative, stakeholders discussed the discovery, development and delivery cycle and the importance of transparent collaboration to bring better treatments to patients sooner.
The Pharmaceutical Research and Manufacturers of America said in a white paper (PhRMA Commentary) that most patients are likely not aware that FDA regulates the medical and scientific information that biopharmaceutical companies may share with healthcare professionals, and thus FDA's regulations have a direct impact on patient care. "Congress should press the FDA to revise its regulations to allow companies to share truthful, scientifically accurate, and data-driven information with healthcare professionals to inform treatment decisions," PhRMA said.
More at links above. (BioCentury and PhRMA)
Dems, GOP call for investigation of federal health IT problems
Senate Democrats have joined Republicans in demanding an investigation into whether heavily subsidized electronic health records systems are blocking the free exchange of patient health information that was a major objective of the multibillion-dollar federal program.
The comments, accompanying a spending bill, signaled that dissatisfaction with the meaningful use program among doctors and health IT professionals was bubbling up in both houses of Congress.
Federal health IT officials have been trying to prompt better health exchange among EHR systems and have made interoperability — the free flow of information among health systems — a central goal of their efforts over the next year. Without freer data exchange, the electronic health records won’t lead to the kind of health care improvements and cost controls sought under the Affordable Care Act and the 2009 HITECH Act, experts say.
The Appropriations Committee asked for a “detailed report” on the extent of information blocking, including an estimate on the number of vendors or eligible hospitals or providers who block information, and how to combat it. It also demanded the Health IT Policy Committee submit a report on the barriers to interoperability. More at link above. (Politico via DIA Daily)
SECTION 6 SOURCES REVIEWED FOR THIS NEWSLETTER
A partial listing of sources reviewed for this newsletter: AdvaMed Smartbrief; AHRQ Newsletter; Alzheimers Association; Alzheimers Research Forum Newsletter; BioCentury; Biopharma Reporter; BIOtechNow; CDISC Monthly Newsletter; CER Daily Newsfeed (NPC); Daily Dose (Becker); DIA Daily; Drug Daily Bulletin; EMA website; EP Vantage; Evaluate Pharma; Eye on FDA; FDA.gov; FDA Law Blog; Federal Register Table of Contents; Fierce Medical Devices; Fierce Pharma; Fierce Vaccines; FDLI Smartbrief; Genomeweb; Health Industry Washington Watch; Government Health IT; Health IT Security; Institute of Medicine News; MedCityNews; Medical Device Daily; Medical Device & Diagnostic Industry; MedPage Today; NPC Bulletin; Nutra Ingredients USA; Pharmabiz; Pharmafile; Pharma IQ; PharmaTimes; PhRMA website; PM Live; Policy and Medicine (newsletter); Regulatory Focus; RegLink News; US FDA Daily Digest Bulletin.