Webinar Q&A follow-up: Manipulation of Abuse Deterrent Formulations at the Clinical Pharmacology Unit

On the 8th June we featured a fantastic live webinar from Scott Smiley (Vince & Associates Clinical Research, an Altasciences company), discussing the development of abuse deterrent formulations (ADFs) as a strategy to help combat the growing opioid epidemic in the USA and worldwide. We learnt more about the need for ADFs, strategies of opioid abuse and abuse prevention as well as the factors that must be taken into account for successful in vivo studies.

We’ve compiled the Q&A section below, including those questions we didn’t have time to answer in the live session, for you to take a look at. Do let us know your thoughts on this topic or any of the questions posed by commenting below this feature!

Where do we start when looking for the best way to manipulate our product?

The best way to start is to go back to the initial drug discovery; look at the chemical and physical make-up of what the product is and what the abuse deterrent mechanism is. A lot of the research should have already been done during development, and if preclinical studies have started a lot of data can also be taken from that. Once we identify whether it’s a physical or chemical method that we need to use then we can start using some general principles and basically it’s a trial and error of what will work and what won’t work for any given product.

Does this apply to generics?

When I initially gave this presentation at a conference back in November that was really a gray area for this. Fortunately, as of March this year the FDA have issued a draft guidance that covers generics with abuse deterrent formulations. A lot of the methodology and procedure are similar but they’ve focused a bit more on the in vitro side and then supplementing that with a lot of in vivo manipulations and testing.

How long should it take to develop the method?

Typically the method can be developed in 1–2 months. There’s a lot of basic testing and analysis that needs to occur; making sure that the method is reproducible, that the particle size will meet the evaluation criteria and that the clinical side can actually reproduce with the same particle size that we’re doing in the lab. Again, the sooner one can start, the more time it gives for you to iron out any bugs that may pop up during the formulation.

When is the best moment to start developing an abuse deterrent formulation across the clinical development plan for a new chemical entity?

The current guidance from the FDA is specific to opioids, however, that does not mean at some later date that abuse deterrent formualtion criteria would be added to stimulants, benzodiazepines, etc.  That being said, if you fall into the opioid class, it really depends on your resources.

Things that need to be addressed are any unique physical or chemical properties of the active pharmaceutical ingredient, route of delivery, immediate or extended/delayed release, etc; you can then evaluate which particular deterrent route you want to do.  If you have unlimited resources, you can start at this point.  If you are like most people, you at least want to show proof of concept before making the commitment to formulate your product.

Typically when conducting the likability studies how many subjects are you trying to enrol?

This is dependent on the statistical model you use (Williams square, Latin square, etc) and the confidence factor assigned.  We typically see a 20% overenrolment in order to obtain the required number of completers.  This may need to be adjusted up dependent on the number of periods and wash out time in between periods.

Have you found there is a most popular way to abuse transdermal patch formulations? Would any of the grinding/mill methods still apply?

The majority of fentanyl patch abuse is by the oral route, which takes very little manipulation.  There are two patches in the pipeline that have abuse deterrence, but I’m not familiar with their mechanism.  In theory, you could quick freeze the gel with liquid nitrogen, mill it to a small particle size, and extract the fentanyl, but I would think this would be extremely difficult to do.