August 2017

· 4 min read

Regulatory Radar: FDA’s Regulatory Actions Target the Prescription Opioid Abuse Crisis

The opioid drug abuse crisis is being addressed as a priority by the FDA and by $1 billion two-year grants to states under the 21st Century Cures Act. In the period of 2002-2015 there has been a nearly three-fold increase in deaths from opioid overdoses with a reported 20,101 overdose deaths related to prescription pain relievers in 2015.1

Recent FDA action on addressing the opioid abuse crisis included the request in June 2017 for a voluntary removal from the market of the opioid drug, Opana ER (extended release) by Endo Pharmaceuticals which marks the first of such request. This action followed a March 2017 Advisory committee vote of 18 to eight that the benefits of the opioid drug Opana ER no longer outweigh its risks. The risk in this case related to abuse of the drug by the intravenous dose route, which was linked to HIV and hepatitis C outbreaks. Interestingly, the company in 2012 had reformulated its product to prevent nasal and intravenous abuse of the drug. Endo Pharmaceuticals has since agreed to the Agency’s request. Had Endo not voluntarily removed the drug from the market, FDA was prepared to withdraw the NDA approval.

FDA called for further action in a July 2017 public workshop which discussed the available data and methods for assessing the impact of opioid formulations with abuse-deterrent properties on opioid misuse, abuse, addiction, overdose and death in the postmarket setting. The aim of the workshop was to improve the analysis and interpretation of existing data, and to discuss opportunities and challenges for collecting and linking existing data to improve national surveillance and research efforts.

Actions called for by the FDA commissioner at this meeting included proposing new guidelines and restrictions on some of the most widely used pain medications and plans for drug product manufacturers to provide doctor education programs on immediate-release (IR) opioids. IR drugs account for about 90 percent of the 200 million opioid painkiller prescriptions written annually in the U.S. Further, the agency is exploring requirement of pain-management training for doctors, nurses, pharmacists and other health care providers.

The recent FDA efforts on opioid abuse are not new and follow its full action plan outlined in February 2016.2 This action plan calls for a range of activities including to:

  • Expand use of advisory committees to be convened before approving any New Drug Application for an opioid that does not have abuse-deterrent properties. The Pediatric Advisory Committee will make recommendations regarding a framework for pediatric opioid labeling before any new labeling is approved. Also, FDA will consult an advisory committee on abuse-deterrent formulations of opioids when they raise a novel issues.
  • Develop warnings and safety information for immediate-release opioid labeling to include additional warnings and safety information that incorporate elements similar to the extended-release/long-acting (ER/LA) opioid analgesics labeling update of 2013.
  • Strengthen postmarket requirements by requiring drug companies to generate postmarket data on the long-term impact of using ER/LA opioids.
  • Update Risk Evaluation and Mitigation Strategy (REMS) program by updating REMS requirements for opioids after considering advisory committee recommendations and review of existing requirements. ER/LA opioids are currently subject to a REMS program that requires sponsors to fund continuing medical education (CME) providers to offer, at low or no cost, CME courses on the appropriate use of these products.
  • Expand access to abuse-deterrent formulations (ADFs) to discourage abuse by making manipulation more difficult or abuse of the manipulated product less attractive or less rewarding. To aid industry efforts in this area, and enhance availability of less costly ADF generic products, FDA issued the guidance General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products (March 2016). This Guidance includes recommendations about the studies that should be conducted to demonstrate that a generic opioid is no less abuse-deterrent than the brand name product that has labeling describing abuse-deterrent properties, with respect to all potential routes of abuse. There are no currently approved generic versions of opioids with approved AD labeling.
  • Support better treatment through increased access to overdose treatment, safer prescribing and use of opioids, and, ultimately, new classes of pain medicines without the same risks as opioids. Options reviewed include over-the-counter availability (e.g. to make naloxone more accessible by making it available over-the-counter to treat opioid overdose).
  • Reassess the risk-benefit approval framework for opioid use by more formal incorporation of public health impact of opioid abuse in approval decisions. This includes seeking advice from the agency’s Science Board and engaging the National Academies of Sciences, Engineering, and Medicine on how to take into account our evolving understanding of the risks of opioids, not only to the patient but to other persons who obtain them. This included a meeting of the Science Board with the FDA in March 2016.

FDA’s efforts have also been exemplified by several guidances to aid industry in understanding how the agency evaluates opioid products, the type of studies that should be performed to evaluate abuse potential and abuse deterrents, and the type of labeling claims that can be made based on results from those studies. This includes the FDA industry guidance documents Abuse-Deterrent Opioids – Evaluation and Labeling (April 2015) and Assessment of Abuse Potential of Drugs (January 2017).

For more detail on what is captured in these guidances, watch for our upcoming blog posts.

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