Posted 24 March 2016 | By Michael Mezher

The US Food and Drug Administration (FDA) released a new draft guidance intended to ensure that generic versions of abuse-deterrent opioids meet the same standards for abuse deterrence as their brand-name counterparts for public comment on Thursday.

The new draft guidance is part of a wider effort by FDA to address the national opioid epidemic, which claimed the lives of more than 28,000 Americans in 2014.

In February, the agency detailed its opioids action plan, saying it would require advisory committee meetings for all new opioid drugs that lack abuse-deterrent properties, strengthen warnings for all immediate-release formulations and increase postmarket requirements to include new studies and updated risk evaluation and mitigation strategy (REMS) requirements for opioids.

While introducing the draft guidance, FDA Commissioner Robert Califf emphasized the importance of opioids in pain management, saying, "For the millions of Americans who suffer from significant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."

Califf then stressed the role of abuse-deterrent formulations in the overall response to the epidemic, saying, "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."

Douglas Throckmorton, deputy director for regulatory programs at the Center for Drug Evaluation and Research, said that bringing generic abuse-deterrent opioids to the market is a priority for FDA, adding that the agency "looks forward to a time when the majority of opioids on the market are in effective, abuse-deterrent formulations."

By releasing the draft guidance, Califf said FDA is facilitating the eventual transition away from non-abuse-deterrent opioids by detailing what steps generic manufacturers need to take to show their products are as abuse-deterrent as their reference products.

Last year, FDA issued a similar guidance aimed at drugmakers developing brand-name abuse-deterrent opioids detailing four categories of studies that should be conducted to demonstrate abuse-deterrence.

Current abuse-deterrent opioids rely on technologies that make it more difficult to abuse the drugs by crushing or dissolving them. To date, FDA has approved five opioids with abuse-deterrent claims that are consistent with its brand-name abuse-deterrence guidance: OxyContin, Targiniq ER, Embeda ER, Hysingla ER and Morphabond.

However, it could be years before any generic abuse-deterrent opioids reach the market. FDA approved the first abuse-deterrent opioid, a reformulation of Purdue Pharma's OxyContin, in 2010. In 2013, the agency approved updated labeling for the new, abuse-deterrent version of OxyContin, and announced that it had withdrawn approval for original version of the drug because its benefits "no longer outweigh its risks," preventing generic manufacturers from marketing copies of the original.

Throckmorton said he couldn't comment on how long it would be before generic abuse-deterrent opioids could be approved, citing patents held by the innovator companies.

When asked whether a generic manufacturer could add abuse-deterrent properties to a copy of an approved non-abuse-deterrent opioid, Throckmorton said that such a proposal would fall outside the scope of the new draft guidance.

However, he said that FDA would "encourage a conversation" with any manufacturers interested in collecting the data necessary to support abuse-deterrent labeling for a generic version of a product without abuse-deterrent properties, noting that he wasn't sure how the agency would categorize such a product.

Califf responded, saying, "Of course we'd be open [to it], but we don't have a pathway for that right now."

Draft Guidance

Throckmorton said the goal of the draft guidance, General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products, is to ensure that generic versions of abuse-deterrent opioids are "no less abuse-deterrent" than their reference products.

Because FDA requires generic drugs to be therapeutically equivalent to their reference products, the draft guidance says it expects generic sponsors to conduct "comparative in vitro studies and, in some cases, in relevant pharmacokinetic or other studies to show that it is no less abuse-deterrent than the [reference drug].

These studies will follow a tier-based approach, "starting with simple and gentle manipulations of the product in in vitro studies and progressing to more destructive mechanical and chemical manipulations until [the reference] product's abuse deterrence is defeated or compromised, or the [generic] product is shown to be less abuse-deterrent."

FDA says it will evaluate the generic product's abuse deterrence based on its performance in these tests, noting that the generic does not need to have the same formulation as its reference product.

To demonstrate this, generic sponsors should test their product and the reference against a non-abuse-deterrent drug, with the same active ingredient if available, in order to compare the products' relative amount of opioid extraction by various routes of abuse: injection (parenteral route), ingestion (oral route), insufflation (nasal route) and smoking (inhalation route).

In addition to the public consultation, Throckmorton said that FDA plans to hold a public meeting to discuss the draft guidance, though it has not yet set a date for the meeting.

Press Release

Draft Guidance