Abuse-deterrent Opioid Strategies

Four presentations covered these distinct topics:

Dr. Nathaniel Katz spoke of the five different types of evidence used in abuse liability and offered informative data on the rates of misuse and abuse. Among thes types described were: in vitro extractability/tampering tests, human abuse liability studies, clinical trials for analgesia, clinical trials for abuse, and epidemiologic studies.

Katz said currently, the dominant format of opioid abuse involves oral administration of products, followed by snorting, but it varies by product. This is why, he said, it is essential for those involved in developing abuse deterrent opioid strategies to examine carefully the preferred method of abuse and create an alternative method of administration that prevents it from being misused.

Robert Brianchi, vice president and chief of Scientific and Technical Affairs for the Prescription Drug Research Center, evaluated the extent to which formulations resist tampering/extraction, and how they fair in testing standards as well as extractability measurement.

Brianchi pointed out that most opioid drug abusers receive the info on how to misuse these drugs from their friends and family, publications, and the internet. In order to prevent abuse and misuse in the forms of tampering, extraction, and other forms, Brianchi said it was essential for manufactures to take certain steps, which include recognizing the products’ vulnerabilities and developing specific experiments catered to them.

Additionally, he recommended each manufacturer engage independent labs and abuse experts in finding solutions for their formulations and consider all modes of abuse.

Dr. Lynn Webster, cofounder and medical director of Lifetree Clinical Research & Pain Clinic, highlighted the latest methods in human abuse liability studies and provided some insight into which type of studies may be appropriate.

Webster spoke about the past of HAL studies and their main focus: In the 1970s HAL studies were used by the DEA for scheduling drugs; and now in 2010, these studies are used by the DEA for scheduling and creating new formulations.

One of the key indicators in using HAL studies in knowing whether or not the drug has abuse potential. For example, psychoactive drugs will almost always be appropriate for HAL studies, he said. HAL studies are designed to provide insight into relative risks of abuse by using surrogate measures in well-defined populations and in controlled settings, he said. While HALs are generally used to create a balance between risk and benefit, Webster said it is essential to be aware of the specific population the tests is being designed for medical abusers or nonmedical abusers.

Edgar H. Adams’ presentation focused on examining clinical trials on analgesia and abuse as well as epidemiological studies and discussed the challenges going into the future.

Adams highlighted an FDA memo to abuse-deterrent opioid drug manufacturing companies that stated these companies would have to demonstrate their findings in the real world before they could actually receive a Claim. Adams said this raises the challenge of now deciphering how large a study needs to be and how long it must last before results will be sufficient to receive a Claim. One suggestion he offered was that manufactures compare rates of addiction in patients with and without a history of addiction and that they incorporate a number of different measures including access to AMP data.

Examining methods used in producing scientific data on abuse potential of new opioids, evaluating types of evidence considered when testing for drug reinforcement properties, and predicating which studies are appropriate in creating abuse-deterrent formulations were the focus of a symposium discussing abuse-deterrent opioid strategies, at the American Pain Society’s 29^th Annual Scientific Meeting.