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FDA urges manufacturers to seek fast approval of “high-need” generics and targeted therapies.
Since confirmation as FDA commissioner in May 2017, Scott Gottlieb has moved aggressively to deliver on promises to Congress and the public to promote innovation while also ensuring medical product safety and patient access to needed therapies. A top priority is to address the deadly opioid epidemic by reducing drug misuse and abuse and encouraging development of safer painkillers. Although FDA officials usually avoid involvement in drug pricing, Gottlieb has addressed the issue head-on, mapping out strategies to accelerate development of competitive generic drugs and biosimilars, as well as initiatives to bring more life-saving therapies to patients.
In addition to these high-profile initiatives, FDA faces the considerable task of implementing the 21st Century Cures legislation. The new law sets tight deadlines for issuing guidance documents, reports, and regulations and for holding public meetings with stakeholders to devise and revise key programs for product development. Cures Act provisions call on FDA to better coordinate the review of combination products and establish a framework for approving regenerative therapies and accelerating the development and approval of critical medicines.
In his first months on the job, Gottlieb also had to overcome administrative hurdles, such as negotiating an exemption for FDA from the administration’s federal hiring freeze. And it appears that Congress will provide a reasonable budget for FDA by ignoring the White House’s proposal to slash agency appropriations and greatly increase user fees. FDA will need considerable resources to accomplish all the goals within the timeframes set by Gottlieb’s multiple action plans.
First on the agenda is the imperative to curb excess prescribing and distribution of powerful opioids and to produce safer alternative pain therapies. To this end, FDA is collaborating with the National Institutes of Health and industry to speed the development of non-addictive analgesics, effective overdose reversal interventions, and better diagnostics that can prevent death from overdose.
At the same time, FDA is examining more closely whether opioids with abuse-deterrent features (ADFs), which FDA has encouraged manufacturers to devise, are effective in resisting misuse or actually aggravate overdosing. In June 2017, FDA urged Endo Pharmaceuticals to pull Opana ER from the market (which the company did in July 2107) due to evidence that abusers merely shifted from snorting the reformulated product to injecting it, igniting outbreaks of HIV, hepatitis C, and a serious blood disorder.
Agency officials are weighing the removal of additional ADFs and examining strategies for evaluating their safety. At a public workshop in July 2017, experts discussed what data and analytical methods could best assess these products, as outlined in an FDA issues paper (1). A new Opioid Policy Steering Committee, headed by FDA Deputy Commissioner Rachel Sherman, is examining whether FDA reviewers sufficiently consider risk of abuse during the evaluation of new pain medicines, along with the adequacy of current dosing recommendations and label information, and whether mandatory education of healthcare professionals is needed to ensure appropriate opioid prescribing (2).
Instead of permitting broader import of cheaper medicines from abroad to expand access to less costly therapies, Gottlieb looks to speed more competitive generic drugs and biosimilars to market. For example, FDA officials say they expect interchangeable biosimilars to appear within two years, following publication of guidance on how to test and develop such products (3). FDA had approved five biosimilars as of June 1, 2017, and manufacturers were developing 66 additional therapies.
Furthermore, a Drug Competition Action Plan outlines strategies for accelerating the review and approval of “high-need,” priority generics and for addressing concerns about brands using Risk Evaluation and Mitigation Strategies (REMS) to block the development of new generic competitors (4). Gottlieb scheduled a public meeting in July 2017 to examine whether innovator firms were gaming FDA rules to block generic-drug sponsors from access to samples needed for bioequivalence testing of abbreviated new drug applications (ANDAs). A related issue is the struggle to negotiate single shared REMS programs for marketing high-risk brand and generic therapies. At the recent meeting, FDA experts heard recommendations from manufacturers and other parties on how to revise the REMS program to halt anticompetitive behavior without undermining new drug development. FDA is accepting comments on these issues through mid-September, and Commissioner Gottlieb is exploring with members of Congress what legislative change is needed in this area and what issues FDA can address with existing authorities.
FDA also seeks to quickly approve additional competitive generics by extending priority review of ANDAs to products with less than three approved alternatives to a reference drug (5). FDA outlined in a June 2017 update to its internal procedures that accelerated review (8 vs. 10 months) applies to drugs with limited competition, as well as to first generics and to products related to drug shortages, public health emergencies, and other special situations (6).
To encourage development of these high-need therapies, the agency also issued a “hit list” of more than 250 branded drugs that are off patent, have no exclusivities, and thus qualify for priority review. The list includes some notorious, high-cost products that are eligible for immediate agency evaluation, and more complex therapies that raise scientific and legal issues and warrant prior consultation with FDA staff (7).
The importance of manufacturer readiness for accelerated approval of priority generics is highlighted in a draft guidance that maps out a new process for identifying and vetting production facilities for priority generics. To enable faster ANDA reviews, FDA wants manufacturers to provide a pre-submission facility correspondence (PFC) two or three months before filing an application for a priority generic product (8). FDA says it needs the extra time to determine if testing facilities and planned manufacturing sites require inspection in order to schedule such visits within the abbreviated review timeframe.
Ultimately, Gottlieb regards the development of more innovative and effective therapies as key to lowering healthcare costs over the long run. Such gains involve streamlining development of treatments for chronic diseases and clarifying R&D requirements to limit unnecessary regulatory costs. The commissioner told the Senate Appropriations subcommittee in June 2017 that a new Medical Innovation Development Plan will address these issues and when FDA may approve a targeted drug based on genetically-defined factors and define more clearly a range of clinical trial enrichment strategies (9).
An initial priority under the Innovation Plan is to spur development of treatments for rare diseases by improving the process for evaluating orphan drug designation requests, which have more than doubled in recent years. By mid-September, according to a new Orphan Drug Modernization Plan, FDA will eliminate its backlog of 200 pending designation requests and establish procedures for vetting such requests within 90 days (10).
Despite these efforts, medical product costs will remain on the table at FDA. “It’s not debatable,” Gottlieb told the Senate Appropriations subcommittee in June 2017, that the United States is subsidizing lower drug prices in other countries through “the high prices we pay here to support research and development.” But whether market competition and more innovation will alter that truism remains to be seen.
1. FDA, “Data and Methods for Evaluating the Impact of Opioid Formulations with Properties Designed to Deter Abuse in the Postmarket Setting,” Issues Paper, CDER, July 10-11, 2017.
2. S. Gottlieb, “FDA Commissioner Asks Staff for ‘More Forceful Steps’ to Stem the Opioid Crisis,” FDA Voice blog post, FDA.gov, May 23, 2017.
3. FDA, Considerations in Demonstrating Interchangeability With a Reference Product Guidance for Industry, Draft Guidance (CDER, CBER, January 2017).
4. S. Gottlieb, “How FDA Plans to Help Consumers Capitalize on Advances in Science,” FDA Voice blog post, FDA.gov, July 7, 2017,
5. FDA, “FDA Tackles Drug Competition to Improve Patient Access,” News Release, June 27, 2017, FDA.gov.
6. CDER, MAPP 5240.3 Rev 3, Policy and Procedures (CDER, June 27, 2017).
7. FDA, List of Off-Patent, Off-Exclusivity Drugs without an Approved Generic.
8. FDA, ANDAs: Pre-Submission Facility Correspondence Associated with Priority Submissions, Guidance for Industry, Draft Guidance (CDER, June 2017).
9. S. Gottlieb, FDA, Draft Testimony, Senate Appropriations Hearing, June 20, 2017.
10. FDA, FDA’s Orphan Drug Modernization Plan, June 29, 2017.
Vol. 30, Issue 8
When referring to this article, please cite it as J. Wechsler, "Gottlieb Tackles Opioids, Drug Costs, and Innovation," BioPharm International 30 (8) 2017.