Medical Device Recalls Increased by 97% Over 10-Year Period
According to a recent report by FDA's Center for Devices and Radiological Health ("CDRH"), the annual number of medical device recalls increased by 97 percent from fiscal year 2003 to fiscal year 2012. The report attributes this increase to enhanced awareness by device manufacturers and specific efforts by FDA to improve medical device safety. Most recalls relate to device design, software, and nonconforming material or component issues. The report says joint action by device manufacturers and CDRH to address these issues could prevent as many as 400 recalls each year. Still, CDRH notes that the significant increase in recalls is not necessarily a sign of declining quality because many recalls are the result of companies exercising more caution after being cited for recall violations in the past.
Senators, JAMA Weigh in on Mobile Medical Apps Regulation
On March 18, a bipartisan group of senators sent a letter to FDA Commissioner Margaret Hamburg urging greater regulatory transparency for mobile medical applications (apps) in order "to avoid stakeholder confusion over how a wider range of medical software might be appropriately regulated." The letter expresses support for the FDA's "risk-based approach" to defining mobile apps, but requests clarification of other aspects, including whether minor software updates require FDA review and how FDA determines whether to regulate novel functions not previously classified by the agency.
States Continue Protest Zohydro Approval; Massachusetts Bans Sales
Several states have protested FDA's approval of hydrocodone drug Zohydro ER based on concerns that a lack of abuse-deterrent features creates a higher-than-acceptable risk of abuse. In March, attorneys general from six states sent a letter to Health and Human Services Secretary Kathleen Sebelius asking her to overturn FDA's approval of Zohydro ER. Last week, Massachusetts Gov. Deval Patrick announced that Zohydro ER may not be sold in the state because its current form does not guard against potential conversion to rapid release. According to Reuters, the manufacturer of Zohydro called the state's ban misguided and noted that other painkillers without abuse-resistant technologies are already on the market. This letter follows similar requests by other state attorneys general and proposals by federal legislators to reverse the drug's regulatory approval.
DEA Acts on FDA Proposed Rescheduling of Hydrocodone Combination Products
In late February, the U.S. Drug Enforcement Agency issued a notice of proposed rulemaking to reschedule hydrocodone combination products from schedule III to schedule II of the Controlled Substances Act ("CSA"). The proposed rule was in response to a recommendation issued by FDA last year around the same time that the agency approved Zohydro (see story above), a single-entity hydrocodone product. Single-entity products are already listed in schedule II of the CSA; however, Zohydro is the first single-entity hydrocodone product to enter the marketplace. Comments on the proposed rule are due April 28.
FDA Considers Reforming Monograph System for OTC Drugs
FDA's Center for Drug Evaluation and Research ("CDER") establishes standards, known as monographs, for over-the-counter ("OTC") therapeutic drug classes. In late March, CDER held a hearing to address pitfalls with the current monograph system and examine potential reforms. CDER Director Janet Woodcock said current challenges include the lengthy, three-phase rulemaking process for promulgating final monographs and the difficulty of keeping up with advances in scientific knowledge and safety information once a monograph is finalized. She suggested adopting an alternative to rulemaking as a way to complete monographs more efficiently. Some attendees at the hearing expressed concerns about changing the monograph system, for example noting that 80 percent of monographs are final and that FDA can establish reasonable schedules within the current procedure to complete the remaining bunch.
FDA Slow to Review Sunscreen Ingredient Applications
A coalition of dermatologists, sunscreen manufacturers, and consumer advocates known as Public Access to SunScreens is urging federal authorities to expedite FDA's approval process for active sunscreen ingredients. According to The Washington Post, the last time that FDA approved a new sunscreen ingredient was in 1999. At least eight applications are pending, including some for ingredients that provide broader protection from UV rays. The article says FDA's review of sunscreen ingredients lags behind similar regulatory processes of other nations, meaning that many beachgoers in Europe and South America have more effective sunscreen than their American counterparts. On March 13, U.S. Sen. Jack Reed (D-RI) and Rep. Ed Whitfield (R-KY) introduced bills aimed at correcting the lags. If enacted, theSunscreen Innovation Act would amend the Food Drug & Cosmetic Act to impose time limits on FDA's review of potential sunscreen ingredients.
More Clinical Trial Data May Become Available in Europe and the United States
The European Parliament is expected to vote this week on a bill that would require pharmaceutical companies and researchers to release the results of each clinical drug trial, including unfavorable results, within a year of the drug trial ending. The Wall Street Journal reports that about half of all trial results are never published. If enacted, the new publication requirements would go into effect in 2016.
FDA Proposes Rule on Medical Device Classification Procedures
In the March 25 Federal Register, FDA issued a proposed rule to amend its regulations governing classification and reclassification of medical devices to conform to the Food and Drug Administration Safety and Innovation Act. For more information, see the Jones Day Alert discussing the proposal.Comments due June 23.
FDA Issues Standard Operating Procedure for Level I, Premarket Data
In the March 26 Federal Register, FDA issued Standard Operating Procedure (SOP) for Level 1, Immediately in Effect (IIE) Guidance Documents on Premarket Data Issues. The standard operating procedure describes CDRH's process to clarify and more quickly inform stakeholders when CDRH has changed its expectations relating to, or otherwise has new scientific information that could affect data submitted as part of, an Investigational Device Exemption or premarket submission, including a Premarket Notification (510(k)), a Premarket Approval, a Humanitarian Device Exemption, or combination products containing a device constituent part for which CDRH has jurisdiction that needs to be disseminated in a timely manner.
FDA Requesting Nominations for Public Advisory Consumer Representatives
In the March 24 Federal Register, FDA issued a notice requesting nominations for voting and/or nonvoting consumer representatives to serve on public advisory committees and panels and asking for any consumer organizations interested in participating in the selection of these representatives to contact FDA. Committees relevant to drugs, medical devices, and biologics include: General and Plastic Surgery Devices Panel, Hematology and Pathology Devices Panel, Orthopaedic and Rehabilitation Devices Panel, National Mammography Quality Assurance Panel, Medical Devices Dispute Resolution Panel, Obstetrics and Gynecology Devices Panel, Pediatrics Advisory Committee, Psychopharmacologic Drugs Advisory Committee, and Reproductive Health Drugs Advisory Committee. The nominations are for current and anticipated vacancies through December 2014. Nominations due April 23.
FDA Issues Direct Final Rule on New Animal Drug Application Confidentiality
On March 17, in a pair of Federal Register notices, FDA amended its regulation on the confidentiality of data and information for new animal drug applications to permit more timely public disclosure of approval-related information, increasing the transparency of FDA decision-making in the approval of new animal drugs. If FDA receives significant adverse comments on the new rule, it will withdraw the Direct Final Ruleand continue to receive comments on the Proposed Rule. Comments due June 2.
FDA Issues Notices to Withdraw Approval of ANDAs for Certain Acetaminophen Drugs
On March 27, in a pair of Federal Register notices, FDA proposed withdrawing approval of abbreviated new drug applications ("ANDAs") from multiple sponsors for prescription pain medications containing more than 325 milligrams (mg) of acetaminophen. The basis for this proposal is that FDA has determined that fixed-combination prescription drugs containing more than 325 mg of acetaminophen per dosage unit (tablet or capsule) do not provide a sufficient margin of safety to protect the public against the serious risk of acetaminophen-induced liver injury. In one notice, the drug sponsors voluntarily withdrew ANDAs, waiving their opportunity for a hearing. The second notice provides an opportunity for hearing. Written requests due April 28.
FDA Issues Draft Bioavailability and Bioequivalence Studies Guidance
On March 18, FDA issued a draft guidance that provides recommendations to applicants planning to include bioavailability ("BA") or bioequivalence ("BE") information for drug products in new drug applications ("NDAs"), investigational new drug applications ("INDs"), and NDA supplements. The guidance sets forth how applicants can satisfy the BA/BE requirements of 21 C.F.R. Part 320 as they apply to dosage forms intended for oral administration. The guidance is meant to assist applicants conducting BA/BE studies during the IND period for an NDA, as well as applicants conducting BE studies during the postapproval period for certain changes to drug products that are the subject of an NDA. Once finalized, the guidance will revise and replace FDA's March 2003 guidance on Bioavailability and Bioequivalence Studies for Orally Administered Drug Products. For more information, see the Jones DayAlert discussing the proposal. Comments due May 19.
FDA Published the Following Additional Guidance Documents:
• Final guidance entitled Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food and Drug Administration Staff: Public Availability of Advisory Committee Members' Financial Interest Information and Waivers.
• Draft guidance entitled Labeling for Human Prescription Drug and Biological Products Approved Under the Accelerated Approval Regulatory Pathway. Comments due May 27.
• Draft guidance entitled Humanitarian Device Exemption (HDE): Questions and Answers. Commentsdue June 16.
• Draft guidance entitled Premarket Notification (510(k)) Submissions for Electrosurgical Devices for General Surgery. Comments due June 23.
• Draft guidance entitled Premarket Notification (510(k)) Submissions for Bipolar Electrosurgical Vessel Sealers for General Surgery. Comments due June 23.
FDA Published the Following Federal Register Notices Regarding Agency Information Collection Activities:
• Approval for collection of information on Recommended Glossary and Educational Outreach to Support Use of Symbols on Labels and in Labeling of In Vitro Diagnostic Devices Intended for Professional Use.
• Opportunity for comment on proposed collection of information on importer's entry notice (commentsdue April 14).
• Opportunity for comment on proposed collection of information on General Administrative Procedures: Citizen Petitions; Petition for Reconsideration or Stay of Action; Advisory Opinions (comments due May 19).
• Opportunity for comment on proposed collection of information on Additional Criteria and Procedures for Classifying Over-the-Counter Drugs as Generally Recognized as Safe and Effective and Not Misbranded(comments due May 23).
Upcoming Meetings, Workshops, and Conferences
Public Workshop on Methods for Thrombogenicity Testing, along with an opportunity for public comment. The meeting will be held April 14 in Silver Spring, MD. Comments are due May 14.
Drugs & Biologics
Public Meeting on Patient-Focused Drug Development for Pulmonary Arterial Hypertension, along with an opportunity for public comment. The meeting, which will be held May 13 in Silver Spring, MD, is part of FDA's commitments under the fifth authorization of the Prescription Drug User Fee Act. Comments are due July 14.
Public Meeting on Study Approaches and Methods to Evaluate the Safety of Drugs and Biological Products During Pregnancy in the Post-Approval Setting, along with an opportunity for public comment. The meeting will be held May 28–29 in Silver Spring, MD. Comments are due June 30.
Advisory Committee Meetings
In addition, FDA is accepting nominations for consumer representatives to fill vacancies on public advisory committees and panels. Nominations are due April 23.
For more comprehensive listings of FDA meetings, please visit these FDA web pages:
Recent Product Recalls
In March, FDA issued a Class I recall notice of certain clinical decision support systems designed to help anesthesiologists identify potential adverse events. FDA applied the highest level recall because some of the systems had exhibited a mismatch of patient data. Last year, the manufacturer issued a voluntary Class II recall to address similar concerns. Other recent device recalls by FDA involved power adapters for certain breast pump models because of loose casings.
Recent drug recalls have included certain homeopathic drug products due to possible penicillin contamination during the fermentation process and certain injection products due to particulate matter contamination.
No biologic products have been posted to FDA's website in the last 60 days.
Click here for a complete listing of FDA Recalls.
Recent Warning Letters
FDA has taken enforcement action against a medical device company for failing to comply with adverse events reporting requirements. FDA also issued a warning letter to a dental device manufacturer for violating manufacturing quality regulations.
FDA continues to take action on pharmaceutical imports that do not comply with Current Good Manufacturing Practice regulations, including recently imposing bans on certain imports from India.
Click here for FDA's Warning Letters Home page (scroll down for listing of recently posted Warning Letters).
According to its website, the Office of Prescription Drug Promotion ("OPDP") has issued no warning letters in the last 30 days.
Click here for a complete listing of 2014 OPDP Warning Letters.
Recent Drug and Device Approvals
FDA approves Otezla to treat psoriatic arthritis (March 21).
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.