FDA Publishes Draft Guidance on Assessing Abuse Deterrence of Generic Opioids

The US Food and Drug Administration (FDA) published a new draft guidance designed to make sure that generic versions of abuse-deterrent opioids fulfill the similar standards for abuse deterrence as their brand-name counterparts for public opinion on 24th March 2016.

The new draft guidance is a component of a broader attempt by FDA to address the national opioid epidemic, which claimed the life of over 28,000 people in America in 2014.

In February, FDA detailed its opioids plan of action, stating it would need advisory committee meetings for all new opioid medications that lack abuse-deterrent properties, strengthen cautions for all immediate release formulations and raise post-market specifications to include new research and modified risk evaluation and mitigation strategy (REMS) specifications for opioids.

While launching the draft guidance, FDA Commissioner Robert Califf highlighted the significance of opioids in pain control, stating, “For the large numbers of Americans who suffer from significant pain, and the health systems that provide them, generic opioids can be a proper and inexpensive choice.”

Califf then emphasized the role of abuse-deterrent formulations in the entire reaction to the epidemic, stating, “We identify that abuse-deterrent technology is even now evolving and is only one piece of a much wider approach to fight the issue of opioid abuse. But highly motivating innovation to maximize access to generic types of abuse-deterrent opioid drugs is an essential element in that strategy.”

Deputy director for regulatory programs at the Center for Drug Evaluation and Research (CDER) Douglas Throckmorton, stated that providing generic abuse-deterrent opioids to the market is a top priority for FDA, including that the FDA “looks ahead to a time when the greater part of opioids on the market are ineffective, abuse-deterrent formulations.”

By launching the draft guidance, Califf said the agency is facilitating the eventual transition away from non-abuse-deterrent opioids by outlining what ways generic producers require to take to show their drugs are as abuse-deterrent as their reference products.

Previous year, FDA released a similar guidance targeted at drug manufacturers developing brand-name abuse-deterrent opioids outlining four types of studies that must be performed to show abuse-deterrence.

Present abuse-deterrent opioids depend on technologies that make it more challenging to abuse the medicines by crushing or dissolving them. To date, FDA has accepted 5 opioids with abuse-deterrent claims that are reliable with its brand-name abuse-deterrence guidance: Embeda ER, Hysingla ER, Morphabond, OxyContin and Targiniq ER.

However, it could be years prior to any generic abuse-deterrent opioids reach the market. FDA accepted the initial abuse-deterrent opioid, a reformulation of Purdue Pharma’s OxyContin, in 2010. In 2013, FDA accepted updated labeling for the new, abuse-deterrent type of OxyContin, and declared that it had withdrawn acceptance for the original version of the drug due to the fact its benefits “no longer overshadow its risks,” stopping generic producers from marketing copies of the original.

Throckmorton stated he couldn’t comment on how long it would be prior to generic abuse-deterrent opioids could be accepted, citing patents held by the innovator companies.

When questioned whether a generic producer could add abuse-deterrent properties to a copy of an accepted non-abuse-deterrent opioid, Throckmorton stated that such a proposal would fall outside the scope of the new draft guidance.

However, he stated that agency would “motivate a conversation” with any producers interested in gathering the data required to support abuse-deterrent labeling for a generic type of a product without abuse-deterrent properties, observing that he wasn’t sure how the agency would classify such a product.

Califf reacted, stating, “Of course we’d be open to it, but we don’t have a process for that at the moment.”

Draft Guidance

Throckmorton stated the objective of the draft guidance titled, General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products, is to make sure that generic types of abuse-deterrent opioids are “no less abuse-deterrent” than their reference products.

Due to the fact FDA needs generic medicines to be therapeutically equal to their reference products, the draft guidance states that it is expecting generic sponsors to perform “relative in vitro studies and, in some situations, appropriate pharmacokinetic or other research to show that it is no less abuse-deterrent than the reference drug.

These studies will comply with a level based approach, “beginning with simple and gentle manipulations of the drug in in-vitro research and moving on to more destructive mechanical and chemical manipulations till the reference product’s abuse deterrence is overcome or compromised, or the generic drug is proven to be less abuse-deterrent.”

FDA states that it will assess the generic product’s abuse deterrence dependent on its performance in these studies, observing that the generic does not require having the same formulation as its reference product.

To illustrate this, generic sponsors must test their product and the reference in opposition to a non-abuse-deterrent drug, with the same active ingredient if accessible, to be able to evaluate the products’ relative quantity of opioid extraction by different routes of abuse: inhalation(smoking), oral (ingestion), parenteral (injection)and nasal (insufflation).

Additionally to the public assessment, Throckmorton stated that FDA plans to keep a public meeting to talk about the draft guidance; however it has not yet set a time frame for the public meeting.