Generic or 505(b)(2)?
- Posted by: Ken Phelps
- Published on: November 29, 2009
Is an opioid product that has abuse resistant characteristics but otherwise the same as the RLD a generic or 505(b)(2)?
Readers will know that Camargo has been involved in many opioid-related projects. We have been to FDA’s DAARP 13 times this past year alone. What is the objective of most of these meetings? For the opioids, it is often to review the special anti-abuse or abuse resistant characteristics of the proposed drug product.
The public concern about opioids is the abuse by some patients and the diversion to others who will abuse the drug. There is an important need for these drugs when used correctly. How to balance this risk/benefit has been the focus of public FDA meetings. Yet, as of now, the FDA cannot define product characteristics that can reduce or eliminate abuse. Importantly for sponsors, the Agency cannot define the studies needed to prove the lack of abuse potential of a drug. What we know is that no label will include abuse resistance (or similar) language without Phase IV (post approval) studies.
There are number of approaches to address the abuse potential. But there are certain assumptions that may or may not be true. One is what the route or means of abuse may be. Drug addicts are a very motivated and creative group. Their objective is to get a fast “high”. Extraction and concentration of the opioid from the drug product is accomplished by many solvents — the strategy may be to develop a formulation that is resistant to solvents. Addicts may grind the tablets or empty the capsule contents and snort the powder. Some will consume alcohol to raise the bioavailability.
But think about this: the drug product must simultaneously be bioequivalent to the RLD and be resistant to abuse. Presumably, the drug still must be extractable in gastric fluid. What we have is a generic that has “special characteristics”. Is this a generic product or a 505(b)(2) product?
The Agency wants to encourage the development of abuse resistant products. The way these products are 505(b)(2)’s is that key information will be allowed in the Special Studies section of the labeling, thus allowing marketing based on the differences from the RLD. We are not talking about simple in vitro studies. The Agency will always insist on clinical relevance. What are the studies needed? The FDA suggests asking the experts. Stay tuned.