US FDA guidance aims to encourage generic abuse-deterrent opioids

Opioid abuse has become an epidemic in the US, with over 90 Americans dying after overdosing on opioids daily, according to the Centers for Disease Control and Prevention​. Solid dose prescription opioids have played a major part in this, due to their potential for abuse via oral, parental, nasal, or inhalation routes.

“Opioids with abuse-deterrent formulations (ADFs) are intended to make certain types of abuse, such as crushing a tablet to snort or dissolving a capsule to inject, more difficult or less rewarding,”​ US Food and Drug Administration (FDA) commissioner Scott Gottlieb said in a statement this week.

But though the Agency has approved 10 such drugs – OxyContin, Targiniq ER, Embeda, Hysingla ER, MorphaBond ER, Xtampza ER, Troxyca ER, Arymo ER, Vantrela ER, RoxyBond – there are currently no generic opioids with abuse-deterrent properties labelling.

Therefore to encourage advancements in this space, the FDA published final guidance for drugmakers developing generic abuse-deterrent opioids this week, recommending the type of studies they should conduct to demonstrate that the generic drug is no less abuse-deterrent than its brand-name counterpart.

“It is important that less costly generic versions of opioids that reference RLDs [reference listed drugs] whose labeling describes abuse-deterrent properties are available to ensure access to safe and effective analgesics for patients who need them,”​ the guidance​ states.

“However, it is also important that the availability of such generics does not exacerbate the public health problems associated with opioid abuse.”​

It therefore “focuses on the general principles for developing and evaluating the abuse deterrence of generic solid oral opioid drug products formulated to incorporate physical or chemical barriers” ​and highlights six principles for evaluating a generic solid oral opioid product:

• Tier-based approach to testing – or hierarchical testing – evaluating abuse-deterrent properties under progressively more challenging conditions
• Performance-based evaluation of abuse deterrence: The evaluation of the abuse deterrence for each potential route of abuse being based on the potential ANDA applicant’s best understanding of the abuse deterrence of the reference drug product for that route
• Most effective manipulation, with the FDA recommending a potential ANDA applicant identifies the most effective manipulation conditions for both the reference and its test product before comparing them
• Sample selection after physical manipulation by selecting an appropriate sample before conducting comparative in vitro studies
• Comparing test and reference products in extraction studies to assess the particular vulnerabilities of the products
• Statistical comparison of test and reference products