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FDA Proposes Abuse-Deterrent Guidelines for Generic Opioids

March 25, 2016
The FDA is setting a standard for companies to develop generic opioids using abuse-deterrent technologies, but there are still challenges to face.

The U.S. Food and Drug Administration (FDA) is encouraging pharmaceutical companies to develop abuse-deterrant formulations of their generic opioids. To help companies, the agency issued draft guidelines, which are similar to the guidelines issued in April 2015 for the development of brand-name opioids.   

FDA issues guides for the development of generic abuse-deterrent opioids.“For the millions of Americans who suffer from significant pain, and the health systems that serve them, generic opioids can be an appropriate and affordable option for patient care,” said FDA Commissioner Robert Califf, MD.

“We recognize that abuse-deterrent technology is still evolving and is only one piece of a much broader strategy to combat the problem of opioid abuse. But strongly encouraging innovation to increase access to generic forms of abuse-deterrent opioid medications is an important element in that strategy,” Dr. Califf said.

The guidance document1 comes as part of a new multi-faceted action plan set out by the FDA in response to the public health crisis of rising rates across the country of opioid-related abuse, addiction, and deaths. The idea behind abuse deterrent formulations (ADF) is to allow an opioid to work correctly when taken as prescribed, but  formulated in such a way that deters misuse and abuse, including making it difficult to snort or inject the drug for a more intense high.

Still in its draft phase, the document is a recommendation to companies, not a legal mandate. It lays out recommended study designs, such as comparative in vitro studies, to be used by companies that wish to apply for FDA approval of an oral generic opioid formulation of an existing ADF opioid product.

Do Abuse-Deterrent Drugs Work?

Abuse-deterrent formulations are designed to prevent someone from crushing or injecting an oral opioid product in order to receive a more intense high. However, while these properties are intended to deter abuse,2,3 this does not necessarily mean they can prevent abuse from happening, as the drug still could just as easily be consumed orally.

While the FDA publicly has stated they want to ensure generic ADF formulations are no less abuse-deterrent than brand-name ADF opioids, there is still a relevant inquiry into whether ADF technologies actually have a measurable effect on curbing opioid abuse in the US, something that could be challenging to determine.

US health care providers wrote around 250 million prescriptions for opioids in 2012. However, according to Douglas Throckmorton, MD, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, the uptake of drugs using ADF technology is “limited,” which could create challenges to investigating the epidemiological impact of ADF technologies. Granted, some research already has been published.

Sessler et al found data suggesting ADF drugs, specifically the reformulated extended-release oxycodone, may have reduced opioid-related fatalities by over 80%.4 However, deaths by overdose are just one spot in the spectrum of illicit opioid use. Studying whether an ADF opioid is preventing a person from abusing the drug is a whole other topic, a challenging one to study given the stigma attached to the disease of addiction.

“Having done research in this area in my academic career – that is, treating drug abuse – these are really hard studies to do just because it’s a delicate subject and getting accurate information on the topic is extraordinarily difficult,” said Dr. Califf.

While the new draft guidance is only a recommendation to companies venturing to produce generic ADF opioids, stakeholders that already have ADF opioids on the market are now obliged by the FDA to fund epidemiological research to assess the efficacy of these technologies at reducing opioid abuse in practice, not just theory.

“There’s a good interchange between experts at the FDA and the companies who are paying for the studies to be done, so I’m hopeful we really will get the answers, but I wouldn’t underestimate the difficulty of really knowing whether someone is abusing an opioid. It’s such a difficult topic to even talk about,” said Dr. Califf.

Incorporating Abuse-Deterrence into the Market

Currently, the five ADF opioid products that are under legal obligation to provide epidemiological data are all extended-release products. However, 90% of all opioid prescriptions in the U.S. are immediate-release drugs. Unfortunately, even if abuse-deterrent technology is indeed a valid asset to curbing prescription drug abuse and mortality, there may be external factors that still could prevent opioid products, especially generic formulations, from incorporating ADF technologies in a timely manner.

Right now, patent claims over reformulated opioid products is a disputed topic in the Federal Circuit. Just this February, a judgment refused Purdue Pharma’s patent for their abuse deterrent reformulated OxyContin product.5

Furthermore, if a patent expires on a listed opioid, companies still can apply for FDA approval of a generic opioid product that does not contain any abuse-deterrent properties, anyway. While the FDA is now committed to convening an expert advisory panel before approving a new drug application for any opioid not containing any abuse-deterrent properties, opioids not containing abuse-deterrent properties can still release to the market.

“The law requires that the agency act in a way that is fair, and in that context, generics that meet that standard generally cannot be kept off the market unless the innovator is removed from the market, as well,” Dr. Throckmorton said.

Also, the new draft guidance does not address current generics to incorporate abuse-deterrent properties – only future generics. However, the agency would still work with sponsors to gather the necessary data to incorporate ADF technology, Dr. Throckmorton said.

The agency plans to conduct a public meeting later this year to discuss the new draft guidance on ADF generic products and the topic of abuse-deterrent technology as a tool to potentially stem prescription drug abuse in the US.

“Collaboration is critical in fostering innovation in the field of abuse deterrence,” Dr. Throckmorton said. “It is essential that a generic product is no less abuse-deterrent than the brand name product. We look forward to actively engaging in discussions to help inform our thinking about the evaluation of abuse-deterrent technologies.”

The FDA encourages stakeholders to submit comments and suggestions about the guidance document over the 60-day draft period, by May 24, 2016. More information can be found here.

Last updated on: March 5, 2019
Continue Reading:
Abuse-Deterrent Guidelines Issued by FDA

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