The Food and Drug Administration (FDA) issued a final guidance for industry, Opioid Use Disorder: Developing Depot Buprenorphine Products for Treatment, that reflects the agency's current thinking on trial designs for depot buprenorphine products. Buprenorphine is a medication used in medication assisted treatments to help people reduce or quit opiates. The FDA states that depot buprenorphine products work by injecting buprenorphine resulting in a solid deposit or depot under the skin. Once the depot is formed, buprenorphine is slowly released by breaking down the depot. This guidance outlines suggestions for developmental programs and trial designs for the generation of depot buprenorphine products.
Product developers should use key parameters (e.g., pharmacokinetic profile, minimum and maximum plasma concentration, and accumulation after many doses) described in the guidance to determine how similar an investigational depot buprenorphine product is to existing, FDA approved depot buprenorphine products. For burprenorphine depot products that are similar to a previously approved depot product, a new efficacy trial may not be necessary given similarities to the approved product. However, if the buprenorphine depot product has novel features relative to approved depot products, the FDA guidance outlines a sequential process for developmental programs to follow.
The guidance then outlines details about trial design, recommended efficacy endpoints, and novel efficacy endpoints related to buprenorphine. Specifically, the FDA indicates that novel efficacy endpoints "are not focused on opioid and other abused drug use assessed by toxicological testing" and provides the following examples:
- Reduction in craving;
- Improvement in sleep or mood; and
- Other patient-reported outcomes.
The guidance also describes circumstances in which an application for depot buprenorphine products may be submitted to section 505(j) or 505(b)(2) of the Federal Food, Drug, and Cosmetic Act to inform developers of the best approach for these products.