Should the FDA revoke approvals for non-abuse deterrent generic opioids?

Posted on 25 March 2015 in Clinical Trials

Author: Linda Hermans, Scientist and Product Specialist

There is a growing public health concern in the US surrounding the misuse and abuse of pain relieving medication, such as opioid analgesics1. A method that is being used to address this concern is the development of abuse-resistant drug formulations, and clinical studies that assess the safety and efficacy of these formulations are considered a high priority by the FDA. Abuse-resistant technologies are designed to make drug manipulation more difficult or to make abuse of the product of manipulation less rewarding.

Clinical trials that are assessing the abuse potential of abuse-resistant formulations are expected to target the route of administration (e.g. tablets that are swallowed whole, crushed, dissolved, etc.) and include an appropriate comparator. Comparators are essential for determining whether an observed reduction in drug abuse potential is due to the product’s abuse-deterrent technology or the result of other factors, such as education, policy changes or other interventions. While guidelines such as these make the regulation of new painkillers easier, they do not directly address issues facing the status of in-market generic painkillers that did not include an investigation of abuse potential at the time of approval.

The FDA has previously based approval decisions for non-abuse-resistant generic painkillers on evidence (or lack thereof) of the safety and supposed decreased abuse potential of its abuse-deterrent counterpart2. Therefore a simple assessment of a drug’s liability for abuse would provide regulatory bodies with invaluable information when making decisions about approvals.

Recently, some US industry trade groups called for stricter legislation on non-abuse-resistant painkillers, suggesting that these products should have their approval revoked3. However, it would seem that re-calling such products for post-marketing studies in which generic painkillers’ liability for abuse are measured relative to appropriate comparators (such as an abuse-resistant formulation) would be an approach more consistent with the FDA’s draft guidance and provide an evidence-based decision.

So, how are these measurements made? Studies are typically conducted with subjects who have a history of drug abuse and the ability to distinguish an active drug from a placebo. A cross-over design is often used in order that direct comparisons between the investigative formulation and the comparator can be made. Using questionnaires and rating scales, subjective measurements are taken at multiple timepoints post-dose to measure how probable it is that the new formulation will be attractive to abusers. Computerized tools, such as the Clinical Trial Information System-Abuse Liability (CTIS-AL), provide a quick and easy method of collecting these data reliably in way that enables cases for approvals to be made effectively.

The trade groups and the FDA are united in their aim to promote both innovations in technology within the drug development space, as well as advocate for patient safety by proactively addressing the public health concern. However, as the regulatory landscape changes subtly with every new entry to the market, and public and political focus fluctuates, decision making for the FDA Controlled Substances division remains challenging.

The use of CTIS-AL allows the objective measurement of the human abuse liability of drug products, making the decision for regulatory bodies easier, complying with FDA guidance and providing fast, accurate results and invaluable information to aid their decision making.


1. Food Drug Administration Center for Drugs Evaluation Research (2010). Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling, FDA Maryland.