The US Food and Drug Administration (FDA) can require opioid generics to have abuse-deterrent properties if the same requirements are applicable to their brand name counterparts, FDA Commissioner Margaret Hamburg said in a letter to Rep. Fred Upton (R-Mich.) last week.
Hamburg’s focus on opioids comes as the number of opioid-related deaths has more than tripled over the past decade in the US, according to the US Centers for Disease Control.
Some of the biggest opioid manufacturers – Pfizer, Purdue Pharma, Endo Pharmaceuticals – are waiting on the FDA to decide on their citizen petitions to keep nonabuse-deterrent opioid generics from Watson Pharmaceuticals and Impax Laboratories, among others, off the market. A decision on Purdue’s petition related to OxyContin (oxycodone HCl) generics is expected later this month.
Last week, the FDA also issued guidance on the development of brand-name abuse-deterrent opioids that aims to provide manufacturers with a better understanding of what types of clinical studies need to be completed before they can make the claim of deterring opioid abuse. Although the guideline does not lay out new requirements for opioid developers, the suggestions provide the basis for what should be included in their new drug applications.
The FDA has yet to approve any abuse-deterrent labels, though Hamburg notes in her letter that the FDA can grant fast-track and priority review status for applications for potentially abuse-deterrent formulations. She added that the FDA will work to determine whether these new formulations actually reduce the abuse and adverse events associated with the abuse of opioids.
More specifically, the guidance lays out three categories of premarketing studies that could help a drugmaker gain approval for its abuse-deterrent opioid, including:
- Lab-based in vitro manipulation and extraction studies to evaluate the ease with which the formulation can be compromised;
- Pharmacokinetic studies to investigate the different properties between the abuse-deterrent opioid and its original counterpart; and
- Clinical abuse potential studies to assess the real-world potential for abuse.
Despite the specifics, the FDA notes that in some cases, not all of these different studies will be required and the agency will take a “flexible, adaptive approach” to evaluating such products. To date, the FDA has limited data supporting the effectiveness of the so-called abuse-deterrent opioids and the agency has never granted such a claim on an opioid’s label.
Impact on the EU
The FDA’s guidance, however, is not likely to have an impact on the EU market for opioids and opioid development because the level of addiction in the EU is not like what it is in the US, Alessandro Pirona, scientific analyst for the European Monitoring Centre for Drugs and Drug Addiction, told in-Pharmatechnologist.com.
Dr. Pirona said the European Medicines Agency is leaving it up to the pharmaceutical companies that develop opioids to track their sales and potential abusers.
Further FDA Efforts
In February, the FDA will meet to discuss the opioid guidance and other questions on the development of abuse-deterrent opioids, whether there needs to be additional prescribing restrictions and whether the labels will be clear enough for patients.
Last summer, the FDA also began requiring all companies that produce extended release and long-acting brand name and generic opioids to include a Risk Evaluation and Mitigation Strategy (REMS) with their products because of the serious risks of the drug. The first continuing education activities under the REMS are expected to be offered to prescribers by March 1.