On March 24, 2016, the US Food and Drug Administration (FDA) published draft guidance to assist applicants who intend to file abbreviated new drug applications (ANDAs) for approval of generic versions of opioid drug products with abuse-deterrent properties. The FDA’s draft guidance follows its April 2015 final guidance for brand name opioids, which marked the first step in establishing a framework for identifying what studies are needed to test an opioid drug product’s abuse-deterrent properties.
The FDA’s new draft guidance outlines a set of general principles for evaluating a generic opioid drug’s abuse-deterrent properties and suggests that ANDA applicants conduct in vitro and other studies to demonstrate that the generic opioid drug equivalent is no less abuse-deterrent than its reference listed drug (RLD) counterpart. The FDA explains that it will consider the “totality of the evidence” presented by the ANDA applicant when making this determination. ANDA applicants are encouraged to be very detailed and comprehensive in their testing to present the best case for a generic equivalent to the FDA for approval.
The FDA encourages ANDA applicants to heed the following principles when evaluating the abuse-deterrent properties of generic opioid drugs against their RLD counterparts:
- ANDA applicants should conduct comprehensive tier-based testing to confirm findings. ANDA applicants should conduct an array of testing, beginning with simple manipulations in in vitro studies (Tier 1) and later performing more aggressive mechanical and chemical manipulations. ANDA applicants should be able to demonstrate that the generic opioid drug’s abuse-deterrent properties surpass the RLD’s same properties.
- Generic products may only be understood after first testing the abuse-deterrent properties of RLD products. ANDA applicants must identify the RLD product’s abuse-deterrent properties for all routes of abuse (e., injection, ingestion, insufflation (nasal), and smoking). If, based on the testing conducted, the RLD product appears to have no abuse-deterrent properties for a particular route of abuse, the FDA encourages ANDA applicants to document the testing conducted and reasons for concluding that the RLD product has no abuse-deterrent properties for that particular route.
- Testing should involve control products. The FDA encourages ANDA applicants to include a control product when comparing generic opioid drugs with their RLD equivalents. The FDA suggests using a non-abuse deterrent version of the RLD product that contains the same active pharmaceutical ingredient (API) as the RLD product. The FDA anticipates that use of appropriate control products and discriminatory testing conditions will enable ANDA applicants to perform the statistical comparisons needed to accurately evaluate the generic and RLD products across all routes of abuse.
- ANDA applicants should evaluate the generic product across multiple strengths and consider additional testing. Where an ANDA applicant seeks approval for multiple strengths of a generic drug, the FDA suggests that the ANDA applicant conduct in vitro studies across all strengths. Further, where there are limited or no reliable in vitro testing methodologies, the FDA suggests that ANDA applicants conduct pharmacokinetic (PK) studies only in healthy volunteers. ANDA applicants should also ensure that the same level of mechanical or chemical manipulations have been applied for both the generic product and its RLD equivalent prior to administration.
The FDA will accept electronic or written comments on the draft guidance until May 24, 2016.
*Blake Walsh is admitted only in Tennessee. Her practice is supervised by principals of the firm admitted in the District of Columbia.