Pharmaceutical & Medical Device Regulatory Update, Vol. II, Issue 8

Pharmaceutical & Medical Device Regulatory Update, Vol. II, Issue 8

Read the Pharmaceutical & Medical Device Regulatory Update, Vol. II, Issue 8 newsletter.


May 3–5, 2015: Scott Edelstein and Alexis Gilroy will speak at the American Telemedicine Association's Annual Meeting in a program titled Telehealth Partnering in US & Abroad—A Look at Viable Strategies & Legal Considerations. Doug Pearson, Bruce Olcott, and Chris Mikson will speak at a pre-conference session titled Digital Health in Transition: Regulatory Insights for Product Developers.

May 13–15, 2015: Laura Laemmle-Weidenfeld will present on the topic of settling fraud and abuse enforcement matters at the American Bar Association's 25th Annual National Institute on Health Care Fraud.

Top News

Court Denies Motion to Delay Launch of First Approved Biosimilar
The first U.S. biosimilar product Zarxio overcame another legal challenge earlier this month when a federal court in California denied a motion to enjoin its commercial launch. The motion was in response to a previous decision in the case, holding that under the patent litigation provisions of the Biologics Price Competition and Innovation Act, the biosimilar applicant was not required to provide its application to the reference product sponsor, a ruling currently on appeal to the Federal Circuit. In a footnote, the judge indicated Zarxio's manufacturer had agreed not to launch the biosimilar product until the earlier of May 11, 2015, or a decision on the pending appeal.

FDA, CMS Create Task Force on Laboratory Developed Tests
On April 16, 2015, FDA and the Centers for Medicare & Medicaid Services ("CMS") announced an interagency task force intended to address stakeholder confusion regarding their respective roles in the regulation of laboratory developed tests ("LDTs"), or diagnostic products made and used in a single lab. The task force will bring together leaders and specialists from each agency to address a range of issues, including quality requirements for LDTs. Last year, FDA issued two draft guidance documents describing the agency's proposed framework for overseeing LDTs, which suggests FDA is gradually moving toward regulating this sector.

CDRH Director: Expedited Access Program Will Hasten Patient Access to New Devices
In a recent blog post, Jeffrey Shuren, director of FDA's Center for Devices and Radiological Health ("CDRH"), discussed a voluntary program by which sponsors of devices that treat life-threatening or irreversibly debilitating conditions may now request Expedited Access Program ("EAP") designation for premarket submissions. The blog post discusses a Data Development Plan, which will shift certain premarket requirements to the postmarket setting. In addition, for EAP-designated devices, FDA may be willing to accept more uncertainty if balanced by other factors, such as the benefits of having earlier access to the device. FDA published two guidance documents on the subject, one outlining the EAP and the other on balancing premarket and postmarket data collection.

European Court of Justice Issues Decision on Pricing of Medicinal Products, Scope of National Health Insurance Systems
The European Court of Justice ("ECJ") has issued a ruling that when a directive relating to the pricing of human medicines requires the removal of a drug from compulsory health insurance, the directive must explain the rationale for that decision. According to the ECJ, the obligation to disclose this information will allow interested parties to verify whether pricing decisions discriminate between national medicinal products and those originating in other Member States.

NIH Issues First Grants for Diagnostic Tools Addressing Antibiotic-Resistant Bacteria
In an effort to reduce the time necessary to identify antibiotic-resistant bacteria, a division of the National Institutes of Health ("NIH") has awarded more than $11 million in first-year funding for nine research projects on the topic. For the grant funding, the National Institute of Allergy and Infectious Diseases selected institutions that are developing rapid diagnostic tests for identifying and characterizing resistant bacteria that frequently cause infections in health care settings.

European Parliament Members Call for Exclusion of Five Health-Related Topics from TTIP Negotiation
On April 14, 2015, members of the Parliament's Committee on the Environment, Public Health and Food Safety ("ENVI") voted in favor of an opinion to exclude certain topics from Transatlantic Trade and Investment Partnership ("TTIP") negotiations. Specifically, ENVI calls for the exclusion of public health services, the REACH law, cloning, bioengineered foods, and the use of hormones in beef.

Other News
FDA Warns Consumers Not to Use Certain Muscle Growth Product

Health Insurers Urge Tighter Rules for Medical Devices Following Morcellator Report

U.S. Marshals Seize Unapproved Drugs from Florida Distributor

Health MEPs Propose Blueprint for Safer Health Care

Germany Set to Tackle Corruption in Health Care

OIG to Examine Increased Prices of Generic Drugs for Effect on Medicare and Medicaid 

Report Indicates 240 New Drugs in Development for Blood Cancers

EU Adopts New Rules for Tracing Tissues and Cells from Human Donors

FDA Issues Guidance on Revising Risk Evaluation and Mitigation Strategies

Utah Governor Signs Biosimilar Substitution Law

Regulatory Notices

FDA Announces Availability of Grants to Support Innovations in Medical Evidence Surveillance Methods
In the April 15, 2015, Federal Register, FDA announced the availability of grant funding through the Reagan-Udall Foundation's program on Innovations in Medical Evidence Development and Surveillance (IMEDS)–Methods. The grants seek to develop new methodologies for FDA to conduct effective post-market safety surveillance of medical products using bulk electronic health care data. Applications are due June 15, 2015. 

CDRH Launches Pilot Program for Database of Home-Use Device Labels
In the April 20, 2015, Federal Register, FDA's CDRH announced it is launching an electronic submissions database of labels and package inserts for listed home-use devices. CDRH invites companies that label device(s) for home use to participate in a Pilot Program, which will provide industry and CDRH staff the opportunity to evaluate the submissions process and system. Requests for participation are due May 31, 2015.

CDRH Solicits Industry Participation in 2015 Experiential Learning Program
In the April 8, 2015, Federal Register, FDA's CDRH announced it is accepting applications from representatives in the medical device industry, academia, and health care profession to participate in its 2015 Experiential Learning Program. The program aims to provide CDRH staff with a better understanding of devices they review through discussions with industry leaders. 

FDA Requests Nominations for Participation on CDER Public Advisory Committees
In the April 15, 2015, Federal Register, FDA announced it is seeking nominations for industry representatives to serve on the public advisory committees for the Center for Drug Evaluation and Research ("CDER"). Organizations interested in helping select the nonvoting representatives should notify FDA. Interest letters and nominations are due May 15, 2015.

FDA Issues Priority Review Voucher for Rare Pediatric Disease Product
In the April 7, 2015, Federal Register, FDA announced it has issued a priority review voucher for Cholbam (cholic acid), pursuant to authority provided in the Food and Drug Administration Safety and Innovation Act. Cholbam is a bile acid indicated for the treatment of bile acid synthesis disorders and other peroxisomal disorders.

FDA Proposes Technical Amendment to Clarify Performance Standard for Ionizing Radiation-Emitting Products
In the April 13, 2015, Federal Register, FDA announced a proposed rule to clarify language in federal performance standards on ionizing radiation. Specifically, the proposal would correct a drafting error in an earlier rule on fluoroscopic equipment measurement.

FDA Withdraws Approval of New Animal Drug Application
In the April 8, 2015, Federal Register, FDA announced that, at the sponsor's request, it is withdrawing approval of a new animal drug application ("NADA") for a fomepizole injectable solution, which is used as an antidote for ethylene glycol poisoning in dogs.

FDA Amends Animal Drug Regulations for Updated Sponsorships
In the April 8, 2015, Federal Register, FDA amended the animal drug regulations to update sponsorships of NADAs and abbreviated new animal drug applications ("ANADAs"). Effective April 8, 2015.

FDA Determines Regulatory Review Periods for Three Drug Patents
In recent issues of the Federal Register, FDA announced determinations of the regulatory review periods for extension of three drug patents: AUBAGIO, ELVITEGRAVIR, and RAVICTI

FDA Issued the Following Draft and Final Guidance Documents
Guidance for Industry and FDA Staff: Expedited Access for Premarket Approval and De Novo Medical Devices Intended for Unmet Medical Need for Life-Threatening or Irreversibly Debilitating Diseases or Conditions, April 13, 2015, Federal Register. Effective April 15, 2015.

Guidance for Industry and FDA Staff: Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval, April 13, 2015, Federal Register.

Guidance for Industry: Risk Evaluation and Mitigation Strategies: Modifications and Revisions, April 7, 2015, Federal Register. Comments are due June 8, 2015.

FDA Announced the Opportunity to Comment on the Following Proposed Information Collections

  • Form FDA 3397, User Fee Cover Sheet\
  • Sun Protection Factor Labeling and Testing Requirements and Drug Facts Labeling for Over-the-Counter Sunscreen Drug Products

FDA Announced that the Following Collections Have Been Submitted to OMB

  • Evaluation of the Food and Drug Administration's "Fresh Empire" Multicultural Youth Tobacco Prevention Campaign
  • Waiver of In Vivo Demonstration of Bioequivalence of Animal Drugs in Soluble Powder Oral Dosage Form Products and Type A Medicated Articles
  • Prominent and Conspicuous Mark of Manufacturers on Single-Use Devices

EU Regulatory Notices

New Rules Address Technical and Import Requirements on Human Tissues and Cells
On April 8, 2015, the European Commission adopted two sets of rules for human tissues and cells aimed at protecting patients in the EU through ensuring high quality and safety standards. Directive (EU) 2015/565 amending Directive 2006/86/EC regarding certain technical requirements for coding human tissues and cells sets out technical requirements that facilitate tracing of all tissues and cells from donor to recipient and vice versa. This will happen through a so-called "Single European Code" and Commission-hosted IT platform ensuring uniform labeling of all tissues and cells distributed in the EU. In addition, Directive (EU) implementing Directive 2004/23/EC regarding the procedures for verifying the equivalent standards of quality and safety of imported tissues and cells covers imports and sets out procedures for ensuring that tissues and cells imported from third-party countries meet the same safety and quality standards as those procured, processed, and distributed exclusively in the EU.

EMA Consults on Common Network Strategy to 2020
The European Medicines Agency ("EMA") and Heads of Medicines Agencies have published the EU Medicines Agencies Network Strategy to 2020. The document deals with four key themes (human health, animal health and human health in relation to veterinary medicines, optimizing the operation of the network, and the global regulatory environment) and outlines the joint key priorities for the network and a high-level strategy to achieve them. Comments are due June 30, 2015.

EMA Recommends Measures for Ibuprofen Use
The EMA Pharmacovigilance Risk Assessment Committee ("PRAC") confirmed a small increase in the risk of cardiovascular problems, such as heart attacks and strokes, in patients taking doses of ibuprofen at or above 2,400 mg per day. PRAC concluded that the benefits of ibuprofen outweigh the risks but recommended updating advice such that high doses of ibuprofen should be avoided in patients with heart disease and circulatory problems or in those who have previously had a heart attack or stroke. 

Study Indicates Adherence to EMA Scientific Advice Increases Success of Marketing Authorization Application
An analysis of marketing authorization application outcomes undertaken by the EMA and its Scientific Advice Working Party has been published in Nature Reviews Drug Discovery. The study found the majority of clinical development plans submitted for scientific advice to the EMA prior to a marketing authorization application were not suitable for future benefit–risk assessment but that companies that changed their clinical development plans in accordance with EMA recommendations were more likely to be granted a marketing authorization.

New Rules Address Butylparaben and Propylparaben in Cosmetics Products
On April 16, 2015, Regulation (EU) No. 1004/2014 entered into force, setting new rules on butylparaben and propylparaben in cosmetics products. According to the new regulation, the maximum concentration of propylparaben and butylparaben cannot exceed 0.14 percent when used individually and, in absence of any indication to the contrary from SCCS, 0.8 percent when mixed with other esters. In addition, cosmetic products designated for children under three containing these substances should display a mandatory warning that these products should not be used on diapered area.

Upcoming Meetings, Workshops, and Conferences

Drugs and Biologics
Public Meeting on Chagas Disease Patient-Focused Drug Development, April 28, 2015, in Silver Spring, MD.

Public Workshop on Methodological Considerations to Address Unmeasured Information about Important Health Factors in Pharmacoepidemiology Studies that Rely on Electronic Healthcare Databases to Evaluate the Safety of Regulated Pharmaceutical Products in the Postapproval Setting, May 4, 2015, in Silver Spring, MD.

Public Meeting on Functional GI Disorders Patient-Focused Drug Development, May 11, 2015, in Silver Spring, MD. 

Public Conference on Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practice, May 13–14, 2015, in Cincinnati, OH.

FDA Science Forum 2015, May 27–28, 2015, in Silver Spring, MD.

FDA Public Workshop titled Preparation for ICH Steering Committee and Expert Working Group Meetings in Fukuoka, Japan, May 15, 2015, in Silver Spring, MD.

Public Workshop on Electronic Cigarettes and Public Health, June 1–2, 2015, in Hyattsville, MD.

FDA/AFDO Conference titled In Motion: Science Transforming Policy in Food, Drug, and Medical Device Regulation, June 20–24, 2015, in Indianapolis, IN.

FDA/PDA Conference titled Mission Possible: Patient-Focused Manufacturing, Quality, and Regulatory Solutions, September 28–30, 2015, in Washington, D.C.

Medical Devices
FDA/Xavier University Global Medical Device Conference (MedCon), May 6–8, 2015, in Cincinnati, OH.

FDA/Biomedical Engineering Society Public Conference on Frontiers in Medical Devices: Innovations in Modeling and Simulations, May 18–20, 2015, in Hyattsville, MD. 

Public Hearing on Generic Drug User Fee Amendments of 2012—Regulatory Science Initiatives, June 5, 2015, in Silver Spring, MD.

FDA/AFDO Conference titled In Motion: Science Transforming Policy in Food, Drug, and Medical Device Regulation, June 20–24, 2015, in Indianapolis, IN.

FDA Public Workshop titled Robotically Assisted Surgical (RAS) Devices: Challenges and Opportunities, July 27–28, 2015, in Silver Spring, MD.

Advisory Committees
April 29, 2015: Joint Meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee and the Oncologic Drug Advisory Committee (to discuss a biologics license application for an oncolytic immunotherapy for the treatment of patients with injectable regionally or distantly metastatic melanoma)

April 30, 2015: Ear, Nose, and Throat Devices Panel of the Medical Devices Advisory Committee (to discuss and make recommendations regarding the classification of Hearing Protectors, Circumaural Hearing Protectors, Middle Ear Inflation Devices, Tactile Hearing Aid Devices, Vestibular Analysis Apparatuses, Speech Training Aids for the Hearing Impaired (Battery Powered or Non-Patient), Speech Training Aids for the Hearing Impaired (AC-powered and Patient-Contact), and Nasal Septal Button Devices)

May 12, 2015: Pulmonary–Allergy Drugs Advisory Committee (to discuss new drug application (NDA) 206038, lumacaftor/ivacaftor combination tablets for oral use, submitted by Vertex Pharmaceuticals, proposed for the treatment of cystic fibrosis in patients age 12 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator gene)

May 12, 2105: Vaccines and Related Biological Products Advisory Committee (to discuss the development and licensure of Ebola vaccines)

May 13, 2015: Blood Products Advisory Committee (to discuss strategies for implementation of serological and nucleic acid testing for Babesia microti in blood donors)

May 14–15, 2015: Gastroenterology and Urology Devices Panel of the Medical Devices Advisory Committee (to discuss recent reports and epidemiologic investigations of transmission of infections associated with the use of duodenoscopes in endoscopic retrograde cholangiopancreatography procedures in hospitals in the United States)

For more comprehensive listings of FDA meetings, please visit these FDA web pages:
Meetings, Conferences, and Workshops (Drugs)
Workshops, Meetings, and Conferences (Biologics)
Workshops and Conferences (Medical Devices)
FDA Advisory Committee Calendar 

Recent Notable Drug and Device Approvals/Clearances

FDA approves first-of-its-kind corneal implant to improve near vision in certain patients (April 17, 2015)

FDA approves first generic Copaxone to treat multiple sclerosis (April 16, 2015)

FDA approves Corlanor to treat heart failure (April 15, 2015)

For additional information on drug and device approvals and clearances, please visit FDA's web pages on Drug Approvals and Databases (includes biologics) and Device Approvals, Denials, and Clearances.

Enforcement Updates

Recent Product Recalls
Since we last reported on enforcement actions in March 2015, FDA posted a notice from the N.C. Board of Pharmacy regarding the recall of certain lots of compounded pharmaceutical products. The notice does not identify specific contaminations but attributes the recall to general concerns about a North Carolina-based pharmacy's ability to ensure the sterility and potency of compounded products distributed in all 50 states. Separately, FDA announced another company's voluntary recall of certain IV solutions used in hemodialysis after samples were found contaminated with particulate matter. There were no recent recalls of medical devices posted on FDA's website.

View a complete listing of FDA Recalls.

Recent Warning Letters
FDA issued warning letters to drug and medical device manufacturers for violations of CGMP ("Current Good Manufacturing Practices"), QSR ("Quality Systems Regulations"), and MDR ("Medical Device Reporting") requirements. In addition, two compounding pharmacies were recently cited for insanitary conditions, including operators using nonsterile gowns and nonsterile facemasks, and for distributing products without proper labels. Both companies were registered as outsourcing facilities under Section 503B of the federal Food, Drug & Cosmetic Act, which requires compliance with certain CGMP provisions.

The agency warned a pharmaceutical manufacturer for CGMP violations, including deficient aseptic and sterilization processes. Demonstrating a continued focus on security, FDA also warned the manufacturer for not having adequate controls to prevent unauthorized access to computer systems and laboratory data.

FDA warned a manufacturer of spirometers and a company that produces knee-replacement devices for several violations, including failures to establish and maintain corrective and preventative actions ("CAPAs"), deficiencies in their complaint handling and MDR processes, and inadequate controls for design validation. Additionally, a contact lens company was cited for not responding to FDA 483 Inspectional Observations, which included failing to implement CAPAs, establish training procedures, and adequately validate software used in production and quality systems.

View FDA's Warning Letters homepage (scroll down for listing of recently posted Warning Letters).

Since we last reported on enforcement actions in March 2015, there have been no new letters uploaded to the Office of Prescription Drug Promotion ("OPDP") database.

View a complete listing of 2015 OPDP Warning Letters.

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