From a technological standpoint, it is understood that the goal of developing 505(b)(2) abuse-deterrent products is to make changes to the API or formulation of a drug that has abuse potential in such a way that it dissuades the abuser from wanting to use the drug and choose something else. However, the real-world problem is determining how can we test the product in a controlled setting. We can’t, so the FDA will not allow labeling to state that the technology is abuse-deterrent until post-marketing studies. So, what can we put on the labeling in order to have a commercially meaningful difference upon which to market our product?

It is possible to get information about the in vitro and in vivo performance of your technology into a couple of sections of the labeling. The FDA will judge whether your technology provides an incremental difference from an existing, non-deterrent product.

In order to get immediate highs, abusers will often attempt to crush the tablets to snort it or extract the actives to inject it. A product designed to be abuse-deterrent does not have to address both of these possibilities in order to get FDA approval (the question of market acceptance is another matter).

There are three types of studies that can be conducted to yield information that may be included on labeling at approval:

• In vitro data: Data from studies designed to evaluate the product’s resistance to attempts to defeat the abuse-deterrent properties. These studies should be based on information from abusers, and must be scientifically rigorous and blinded.

• Pharmacokinetic data: Data from studies that evaluate the effects of different methods of physical manipulation identified in the in vitro studies on the pharmacokinetic profile.

• Clinical data (human liking studies): Data from studies of experienced drug abusers to evaluate the likability and euphorigenic effects of manipulated and intact product compared to the product that is not tamper resistant.

A major point to consider is that it is possible to design studies to measure differences between test and reference products, but we often do not know which measures are important in the real world and how much difference is enough to deter abuse. This is why FDA won’t allow the words “abuse-deterrent” on labeling without actual experience studies post-approval.

Premier Consulting considers these issues and discusses them with FDA every month. We can say that the standards are evolving.