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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: August 22, 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CDER Guidances: New/Revised/Withdrawn through 6/30/14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lead to the List of Guidance Documents (CDER) updated on July 7, 2014, and to CDER Guidances that are new, revised, or withdrawn through the second calendar quarter of 2014.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 August 19, 2014, FDA announced the availability of the guidance entitled “Food and Drug Administration Decisions for Investigational Device Exemption Clinical Investigations.”  This guidance document was developed to promote the initiation of clinical investigations to evaluate medical devices under FDA’s IDE regulations. The guidance is intended to provide clarification regarding the regulatory implications of the decisions that FDA may render based on review of an IDE and to provide a general explanation of the reasons for those decisions. [Federal Register]

FDA will hold a webinar on this guidance on September 4, 2014, from 1 – 2:30 PM EDT.  To hear the presentation and ask questions: Dial: 888-972-7807; passcode: 1405152.

To view the slide presentation during the webinar: https://www.mymeetings.com/nc/join/
Conference number: PW8306690 Passcode: CDRH

On August 19, 2014, FDA announced a public hearing to solicit public comment on certain topics related to implementation of the “Generic Drug User Fee Amendments of 2012 (GDUFA)” and the GDUFA Commitment Letter that accompanies the legislation.   The public hearing also will provide an opportunity for public input on future policy priorities. FDA is seeking participation in the public hearing and written comments from all interested parties, including, but not limited to, regulated industry, consumers, patients, caregivers, health care professionals, and patient groups.  The public hearing will take place on September 17, 2014 at College Park Marriott Hotel and Conference Center, Hyattsville, MD.  Comments will be accepted after the hearing until  [Federal Register]

On August 20, 2014, FDA issued a “Request for Nominations for Voting and/or Nonvoting Consumer Representatives on Public Advisory Committees or Panels, and Request for Notification From Consumer Organizations Interested in Participating in the Selection Process for Nominations for Voting and/or Nonvoting Consumer Representatives on Public Advisory Committees or Panels.” Nominees recommended to serve as a voting or nonvoting consumer representative may be self-nominated or may be nominated by a consumer organization. Nominations will be accepted for current vacancies and for those that will or may occur through December 2014. [Federal Register]

On August 22, 2014, FDA issued a proposal to amend the biologics regulations entitled “Revocation of General Safety Test Regulations That Are Duplicative of Requirements in Biological License Applications.”  FDA is proposing to amend the biologics regulations by removing the general safety test (GST) requirements for biological products. FDA is proposing this action because the existing codified GST regulations are duplicative of requirements that are also specified in biologics licenses, or are no longer necessary or appropriate to help ensure the safety, purity, and potency of licensed biological products.  Comments should be submitted by November 20, 2014.  [Federal Register]

On August 22, 2014, FDA announced the availability of the guidance entitled “Evaluation of Sex-Specific Data in Medical Device Clinical Studies; Guidance for Industry and Food and Drug Administration Staff.”   This document provides guidance on the study and evaluation of sex-specific data in medical device clinical studies, and it outlines the Center for Devices and Radiological Health’s (CDRH’s) and Center for Biologics Evaluation and Research’s (CBER’s) expectations regarding sex-specific patient enrollment, data analysis, and reporting of device study information. The guidance is intended to improve the quality and consistency of available data regarding the performance of medical devices in both sexes by encouraging appropriate enrollment by sex in clinical studies of devices, and appropriate interpretation and assessment if data from such studies are analyzed by sex.  [Federal Register]

FDA also released the “FDA Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data.”  The action plan includes 27 action items that are designed to meet three overarching priorities – improving the completeness and quality of demographic subgroup data collection, reporting and analysis (quality); identifying barriers to subgroup enrollment in clinical trials and employing strategies to encourage greater participation (participation); and, making demographic subgroup data more available and transparent (transparency). [FDA.gov]  

On August 22, 2014, FDA announced the “Reopening of Docket and Request for Comments on the Food and Drug Administration Safety and Innovation Act Action Plan.”   The action plan is to contain recommendations, as appropriate, to improve the completeness and quality of analyses of data on demographic subgroups in summaries of product safety and effectiveness and in labeling; on the inclusion of such data, or the lack of availability of such data in labeling; and on ways to improve public availability of such data to patients, health care providers, and researchers. Comments should be submitted by October 21, 2014. [Federal Register]


SECTION 2 FDA NOTES & RELATED NEWS

Updated List of CDER Key Officials Posted

FDA Announces Notice for Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant 
FDA announced pm August 19, 2014, the availability of grant funds for the support of FDA’s Office of Orphan Products Development grant program. The goal of FDA’s Orphan Products Development (OPD) grant program is to support the clinical development of products for use in rare diseases or conditions where no current therapy exists or where the proposed product will be superior to the existing therapy.  FDA provides grants for clinical studies on safety and/or effectiveness that will either result in, or substantially contribute to, market approval of these products.

The opening date is December 4, 2014.  The first application due date is February 4, 2015, with start date of November 2015.  More at link above. (FDA.gov)

Providing Easy Access to Medical Device Reports Submitted to FDA since the Early 1990s
Medical device safety issue reports due to risks not identified in prior studies, malfunctions, problems with manufacturing, or misuse are collected in a publicly available FDA database called MAUDE – short for Manufacturer and User Facility Device Experience.  As part of the openFDA project, there is now an Application Programming Interface (API) for this dataset, which provides a way for software to interact directly with the data. This API will allow developers and researchers to easily query thousands of reports dating back to the early 1990s. 

The API can be a powerful tool for generating hypotheses for further investigation or inquiry and can inform the development of safer, more effective technologies.  More at link above.  (FDA.gov)

Office of Device Evaluation: Foreman Moving to Center for Tobacco Products
Christy Foreman, director of CDRH’s Office of Device Evaluation (ODE), has accepted a new position at FDA’s Center for Tobacco Products, beginning Sept. 7, 2014.  At that time, Dr. William Maisel will begin serving as ODE’s acting director as we conduct a search for a permanent replacement. Dr. Maisel will continue to serve as CDRH’s deputy director for science and chief scientist. (FDA.gov)

Implementing the Generic Drug User Fee Act: Struggles and Successes
Two years into the Generic Drug User Fee Act (GDUFA) program, enacted in July 2012, FDA officials are striving to meet goals and timelines for speeding new generic drugs to market. Agency reviewers have made some progress in eliminating the huge backlog in abbreviated new drug applications (ANDAs) pending in the Office of Generic Drugs (OGD), but not as quickly as manufacturers had anticipated. New guidance from FDA aims to help manufacturers meet standards and to streamline oversight. But a continual rise in submissions to the agency makes it hard for reviewers to get ahead, especially in the wake of a surge of 600 ANDAs filed in June to beat new stability testing requirements.  More at link above. (PharmExec)


SECTION 3 AGENCY AND ADVISORY COMMITTEE MEETINGS

Patient-Focused Drug Development: Disease Area Meetings Planned for FY2013-2015

Public Meeting. Nonprescription Drugs Advisory Committee Meeting.  September 3, 2014. White Oak Campus, Silver Spring, MD.   The committee will discuss the standards used to demonstrate that over-the-counter (OTC) topical antiseptics used in healthcare settings are generally recognized as safe and effective.  [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]

Public Workshop. Clinical Development of Drugs for the Prevention of Infections Caused by Staphylococcus aureus in the Health Care Setting. September 5, 2014.  White Oak Campus, Silver Spring, MD.  This public workshop is intended to provide information for and gain perspective from health care providers, patients and patient advocacy organizations, academia, and industry on various aspects of clinical development of drugs to prevent Staphylococcus aureus infections including the design of clinical trials. [Federal Register]

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. Cellular, Tissue and Gene Therapies Advisory Committee. September 17, 2014. Hyattsville, MD.  In open session, the committee will hear updates of research programs in the Laboratory of Biochemistry, Division of Therapeutic Proteins, the Laboratory of Molecular Oncology and the Laboratory of Molecular and Developmental Immunology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, FDA. Another portion of the meeting will be closed to the public.  [Federal Register]

New:  Public Hearing.  Generic Drug User Fee Amendments of 2012: Public Hearing on Policy Development.   September 17, 2014.  Hyattsville, MD.  FDA seeks input on the five draft guidance documents FDA has issued or will issue shortly to facilitate implementation of GDUFA. FDA also seeks input on additional policy priorities under GDUFA, such as the Agency’s consideration of generic drug exclusivity and the category of first generics. FDA will take the information from the public meeting into account in developing the fiscal year 2015 GDUFA priorities. [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 18, 2014. White Oak Campus, Silver Spring, 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]

Public Meeting.  Patient-Focused Drug Development and Scientific Workshop on Female Sexual Dysfunction.   October 27-28, 2014.  White Oak Campus, Silver Spring, MD.  FDA is conducting a Patient-Focused Drug Development public meeting and scientific workshop on Female Sexual Dysfunction (FSD).  [Federal Register]

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]

New:  Public Workshop. Brain-Computer Interface Devices for Patients With Paralysis and Amputation. November 21, 2014.  White Oak Campus, Silver Spring, MD.  The purpose of this workshop is to obtain public feedback on scientific, clinical, and regulatory considerations associated with BCI (Brain-Computer Interface) devices. Ideas and suggestions generated during this workshop may facilitate development of draft guidance to provide our initial thoughts regarding the content of premarket submissions for emerging BCI technologies to help speed development and approval of future submissions.  [Federal Register]


SECTION 4 OTHER REGULATORY AUTHORITIES & ORGANIZATIONS

PCORI Offers up to $90 Million in Funding in Third Call for Large Pragmatic Studies Proposals
The Patient-Centered Outcomes Research Institute (PCORI) on August 18, 2014, issued the third funding announcement under its Pragmatic Clinical Studies initiative, offering up to $90 million in support for studies that address practical comparative questions faced by patients, clinicians, and other healthcare decision makers.

PCORI will provide up to $10 million in direct costs for studies lasting up to five years through this funding opportunity.

The latest announcement includes in its list of research priorities three new topics where additional research is needed to fill important evidence gaps and that were identified as priorities through the help of one of PCORI’s multi-stakeholder advisory panels.

The new topic areas are:

  • Comparative effectiveness of medical treatments versus invasive procedures for patients with asymptomatic carotid artery disease
  • Comparative effectiveness of different surgical options for hip fracture in older patients
  • Comparative effectiveness of different types of surgical mesh as well as the use versus non-use of mesh in repair of pelvic floor dysfunction.
More at link above.  (PCORI.org)

R2HC issues call for Ebola research proposals
The Research for Health in Humanitarian Crises (R2HC) program launched an emergency call for proposals to support research on experimental Ebola therapies and vaccines, with a focus on clinical trials that could begin during the current outbreak. Proposals are due Sept. 8. R2HC was launched last year by the not-for-profit Enhancing Learning and Research for Humanitarian Assistance (ELRHA) and investors the Wellcome Trust and the U.K.'s Department for International Development. The two investors put in L6.5 million ($10.9 million). The goal was to support collaborative research on public health challenges in low- and middle-income countries.

The call for proposals follows a WHO statement last week that endorsed investigational Ebola compounds that have not yet been evaluated for safety and efficacy in humans. The organization said use of the compounds is ethical as long as certain conditions are met.  (BioCentury)

NIH Announces Launch of Three Integrated Precision Medicine Trials
The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials, or ALCHEMIST, was launched on Monday August 18, 2014, to identify early-stage lung cancer patients with tumors that harbor certain uncommon genetic changes and evaluate whether drug treatments targeted against those changes can lead to improved survival.

ALCHEMIST is supported by the NCI, part of the National Institutes of Health, with coordination of the component trials by the Alliance for Clinical Trials in Oncology and the ECOG-ACRIN Cancer Research Group. All of the NCI-supported National Clinical Trials Network (NCTN) groups collaborated in the development of ALCHEMIST and are participating in the component trials.  More at link above.  (NIH)

Community Health Systems Network Hacked; More than 4 Million Patient Records Stolen
A large number of national and local news sources reported earlier this week on a large-scale hacking attack affecting millions of individuals who have interacted with a national health system. A summary of this coverage is available in the DIA Daily, August 19, 2014.  The Associated Press article reports:

“Hospital operator Community Health Systems said a cyber-attack took information on more than 4 million patients from its computer network earlier this year.

The Franklin, Tennessee, company said Monday that no medical or credit card records were taken in the attack, which may have happened in April and June. But Community said the attack did bypass its security systems to take patient names, addresses, birthdates, and phone and Social Security numbers.

The hospital operator said it believes the attack came from a group in China that used sophisticated malware and technology to get the information. Community Health has since removed the malware from its system and finalized "other remediation efforts" to prevent future attacks.  More at link above. (AP)

FBI warns healthcare firms they are targeted by hackers
The FBI has warned that healthcare industry companies are being targeted by hackers, publicizing the issue following an attack on U.S. hospital group Community Health Systems Inc that resulted in the theft of millions of patient records. 

"The FBI has observed malicious actors targeting healthcare related systems, perhaps for the purpose of obtaining Protected Healthcare Information (PHI) and/or Personally Identifiable Information (PII)," the agency said in a "Flash" alert obtained by Reuters on Wednesday.

"These actors have also been seen targeting multiple companies in the healthcare and medical device industry typically targeting valuable intellectual property, such as medical device and equipment development data," the one page document said.  More at link above. (Reuters)

China calls for greater use of homegrown medical devices
China may use incentives to encourage domestic hospitals to use Chinese-made medical devices as it looks to stimulate the local market and reduce soaring healthcare costs, a potential threat to the global firms who currently dominate the sector. Global medical device makers, especially from the United States, Europe and Japan, now dominate around three-quarters of China's medical device market, which was worth 212 billion yuan ($34.51 billion) last year, according to figures from the Hong Kong Trade and Development Council (HKTDC).

China will speed up the development of its medical device industry and promote wider use of local products to "effectively control unreasonable increases in the cost of medical care and reduce the burden on patients," the country's health ministry said in a statement posted on its website on Monday.  More at link above. (Reuters)


SECTION 5 LEGAL AND COMPLIANCE

DEA to impose tougher restrictions on hydrocodone combos
The U.S. Drug Enforcement Agency issued a final rule raising all hydrocodone combination products to a class II schedule from class III, where class I indicates the highest potential for abuse and class V the lowest. The change will place greater restrictions on hydrocodone combination products, including requiring written prescriptions that cannot be refilled. The final rule takes effect on Oct. 6.

Last year, HHS formally recommended DEA raise hydrocodone combination products to the class II schedule. Pure hydrocodone products are already class II.  (BioCentury)

Do Dying Patients Have a Right to Try Experimental Drugs?
In November, Arizona voters will decide whether terminally ill patients should be allowed to take drugs that are in the early stages of testing but haven’t yet been approved by the U.S. Food and Drug Administration. Similar “right to try” laws have been enacted this year in Colorado, Louisiana, and Missouri.

The laws aren’t a response to demands from patients or lobbying by big drug companies. They’ve been promoted by the libertarian Goldwater Institute, named for Senator Barry Goldwater, the late Arizona Republican. “Our objective is to look at different problems out there and come up with solutions that are liberty-based solutions,” says Victor Riches, the group’s vice president for external affairs. “These individual patients have a right to try a medication to try to save their own life.”

The FDA’s modern drug approval process dates to 1962, when Congress began requiring companies to conduct rigorous clinical trials to prove new medicines were safe and effective. That law was passed amid outrage over thalidomide, a sedative prescribed to pregnant women suffering from morning sickness that caused thousands of birth defects in Europe, Canada, and the U.S.  (Bloomberg Businessweek)


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.