FDA 2017 Year In Review

Introduction

The US Food and Drug Administration's (FDA's) 2017 regulatory agenda was marked by inactivity in the months following the presidential inauguration. Since FDA Commissioner Scott Gottlieb's Senate confirmation in May 2017, the agency has implemented a number of initiatives that were in the pipeline from the prior administration as well as several new legislative and regulatory mandates. FDA has taken steps to reduce regulatory barriers to market entry for innovative products, identified outdated guidance and regulations that will be eliminated or modified, implemented key provisions of the 21st Century Cures Act and emphasized global harmonization. FDA issued important rulemakings and guidance documents throughout 2017, especially in the latter half of the year.

In this article we review notable legislation, regulations, guidance and enforcement actions that shaped FDA-regulated industries and products in 2017 and offer insight into the agency's 2018 priorities and expected actions.

FDA Reauthorization Act of 2017

On August 18, 2017, President Trump signed the FDA Reauthorization Act of 2017 (FDARA) into law. The legislation contained substantive provisions on drugs, devices and pediatric studies in addition to the typical user fee program reauthorizations viewed as "must-pass" legislation every five years.

Reauthorization of User Fee Programs

FDARA reauthorized four user fee programs for an additional five fiscal years: Prescription Drug User Fee Act, Medical Device User Fee Amendments, Generic Drug User Fee Amendments and Biosimilar User Fee Act. In FDARA, Congress also modified existing user fee programs and created additional performance and other data reporting requirements. For example, in the title reauthorizing medical device user fees, Congress added a new fee to handle to handle the increasing number of de novo device classification requests, which apply to novel devices for which there is no currently marketed "predicate." That user fee provision does not apply where a device's proposed conditions of use are solely for a pediatric population. As another example, the title reauthorizing biosimilar biological product user fees eliminated the requirement that an independent accounting or consulting firm study FDA's workload volume and costs associated with the process for the review of biosimilar biological product applications.

Key Drug Provisions

Title VIII of FDARA contained provisions on improving generic drug access, which followed FDA's June 2017 efforts to encourage the submission of abbreviated new drug applications (ANDAs) for off-patent, off-exclusivity drugs with no approved ANDA by publishing a list of such drugs. FDARA mandates updates to the list every six months. FDARA also requires priority review and action on ANDAs submitted for drugs with not more than three approved drug products that are off-patent and off-exclusivity, effectively codifying FDA's June 2017 policy announcement that the agency would prioritize review of ANDAs until there were three approved generics. The agency must prioritize ANDAs for drugs on the drug shortage list and may expedite review of ANDAs for "competitive generic therapies" if there is "inadequate generic competition"—not more than one approved drug that is the reference listed drug (RLD) or a generic drug with the same RLD as the drug for which designation as a competitive generic therapy is sought. FDARA created a new 180-day exclusivity period for first approved applicants of competitive generic therapies, provided the applicant markets the competitive generic therapy within 75 days of the application's approval.

FDARA created new marketing status reporting requirements for holders of new drug applications (NDAs) and ANDAs. By February 14, 2018, NDA and ANDA holders must review the Orange Book (i.e., FDA's Approved Drug Products with Therapeutic Equivalence Evaluations) and submit a one-time report to FDA that states whether the drugs listed in the active section of the Orange Book are available for sale, were never available for sale or have been withdrawn from sale. Holders of approved applications under Federal Food, Drug, and Cosmetic Act (FDCA) sections 505(c) or (j) must now notify FDA 180 days prior to withdrawing the approved drug from sale or as soon as practicable, and must notify FDA if the approved drug will not be available for sale within 180 days of the approval date.

The law also amended the definition of "patient experience data" submitted as part of an NDA or Biologics License Application to include physical and psychosocial impacts of a disease or condition or related therapy or clinical investigation. FDARA permits FDA to require responsible persons to include, as part of a Risk Evaluation and Mitigation Strategies plan, information about limitations or patient care implications of drug formulations or properties, and how such formulations or properties may be related to serious adverse events. FDARA increased penalties for knowingly making, selling, dispensing, or holding for sale or dispensing counterfeit drugs.

Key Device Provisions

FDARA changed FDA's inspection schedule of device establishments from every two years to a risk-based schedule to be created by the agency, which may take into consideration a device establishment's participation in international device audit programs in which the United States participates or that it recognizes. The law requires FDA to issue draft and final guidance regarding amendments to the inspection process for foreign and domestic device establishments, that include a requirement for FDA to provide nonbinding feedback within 45 days of a request by an owner, operator or agent in charge related to proposed actions that involve a public health priority, implicate major or systemic actions, or relate to emerging safety issues. FDARA also reauthorized the third-party inspection program for five more years and, regardless of other statutory provisions regarding inspections by accredited persons, permits the FDA to recognize auditing organizations that are recognized by organizations established by governments to facilitate international harmonization for conducting inspections of device establishments.

FDARA amended provisions regarding the process for initial classification and reclassification of an accessory by which FDA may classify an accessory based on the risk of the accessory when used as intended and the level of regulatory controls necessary to provide a reasonable assurance of the accessory's safety and effectiveness, regardless of the classification of a device with which the accessory is intended to be used. FDARA also amended the approval, clearance or classification of diagnostic imaging devices (applicable medical imaging devices) that use approved contrast agents in different concentrations, rates of administration or routes of administration; different regions, organs or systems of the body; different patient populations; or different imaging modalities than in the contrast agent's approved labeling. The legislation also added new types of devices to the list of devices that are not appropriate for the third-party accredited persons review program, including devices intended to be permanently implanted, life-supporting devices and life-sustaining devices.

FDARA included several provisions regarding medical device pilot programs. For example, the law required FDA to establish a new conformity assessment pilot program under which testing laboratories may become accredited to assess the conformance of a device with performance standards necessary to provide reasonable assurance of safety and effectiveness. FDARA also permits voluntary post-market pilot programs that use electronic health data to provide information on the safety and effectiveness of approved medical devices. The law also contained provisions regarding specific devices, such as over-the-counter hearing aids, on which FDA must issue regulations. FDARA preempts state and local laws that would restrict or interfere with the servicing, marketing, sale, dispensing, use, customer support or distribution of such hearing aids.

Provisions Regarding Pediatric Drugs and Devices

Title V of FDARA included changes to existing laws and reporting requirements related to pediatric studies, pediatric cancer, pediatric drug labeling and pediatric devices. FDARA also required FDA to hold public meetings on pediatric medical devices and molecularly targeted cancer drugs. The agency must issue final guidance on molecularly targeted cancer drugs and draft guidance on clinical pharmacology considerations for neonatal studies of drugs and biologics within two years of FDARA's enactment.

Generic Drugs

Developments in 2017

As noted, since Commissioner Gottlieb's confirmation, FDA has taken several actions to increase generic competition, and Congress also mandated efforts aimed at enhancing generic competition in FDARA. In June 2017, FDA released two lists of off-patent pharmaceuticals with limited or no competition. The first includes drugs "for which FDA could immediately accept an ANDA without prior discussion," and the second is for drugs "involving potential legal, regulatory, or scientific issues which should be addressed with the agency prior to submission of an ANDA." FDA intends to develop a similar list for individual NDA drug products that lack competition. FDA also updated its Manual of Policies and Procedures (MAPP) 5240.3 Rev. 3, Review Order of Original ANDAs, Amendments, and Supplements, to prioritize the review of ANDAs for which there are fewer than three ANDAs approved for the RLD.

The lists and changes to the MAPP are part of FDA's implementation of FDARA and the agency's Drug Competition Action Plan, an overall initiative to balance innovation with access and price-reducing measures for drugs. The agency also held a public meeting in July 2017 to receive input on these issues.

Looking Ahead to...