The final guidance, released Wednesday, offers an explanation for the types of premarket and post-market studies that developers should use in order to gain the labelling that reflect a product’s abuse-deterrent properties, as supported by the data, but “should include a caveat that abuse is still possible” as deterrence does not equal abuse-proof.
Possible abuse deterrent properties, according to the FDA, include physical/chemical barriers to abuse, agonist/antagonist combinations to interfere with the euphoria related to abuse, aversion techniques to create unpleasant effects if a dosage form is manipulated, new molecular entities and prodrugs, a combination of one of the aforementioned and other novel approaches to abuse deterrence.
Douglas Throckmorton, deputy director of regulatory programs at the Center for Drug Evaluation and Research at FDA, said in a conference call on Wednesday that the agency has spoken with over 30 interested manufacturers and that he hopes the final guidance lays out a “roadmap” to help them in their pursuit of developing new opioids.
Examples of information for inclusion in labelling for different types of abuse-deterrent effects – which are basically the carrots for new abuse deterrence tech -- are based on various types of premarket studies.
“In most cases,” the agency says, “to obtain a full and scientifically rigorous understanding of the impact of a technology or technologies on a product’s abuse potential, data from each of the following three categories of premarket studies” are appropriate: Lab-based in vitro manipulation and extraction studies; pharmacokinetic studies; clinical abuse potential studies; and post-market studies.
These include products for which in vitro data demonstrated that an abuse-deterrent product cannot be crushed and dissolved or extracted in a small volume of solution; in vitro and pharmacokinetic data from study of the oral and nasal routes of administration demonstrating that no changes occurred in the extended-release properties of the opioid after crushing or dissolution; and pharmacokinetic and clinical abuse potential studies demonstrating the release of an antagonist from an opioid and antagonist combination product following crushing and that the presence of the antagonist resulted in less drug liking compared to a similar amount of opioid alone.
FDA is also “currently considering formal studies plus a variety of supportive information (e.g., data concerning the street value of prescription drugs) as sources that may be acceptable to provide evidence that a product’s formulation has had an actual impact on reducing its abuse,” the agency said.
The guidance, however, does not apply to or address generic opioid products, which control about 80% of the current market. The agency said it is working on draft guidance in this area.