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Agency is trying to quantify the effects of abuse-deterrent formulations
While there are now a number of opioid pain drugs or other opioid-based controlled substances on the market, the methodology for making a label claim of such deterrence has been lacking. To address this, FDA has now issued draft guidance that lays out both the clinical research process for evaluating deterrence, and its thinking on how deterrence could become part of a label claim. “An important step towards the goal of creating safer opioids is the development of products that are specifically formulated to deter abuse,” said Dr. Douglas Throckmorton, deputy director for regulatory programs at CDER. The comment period will end in early March.
Most drug developers are concerned with demonstrating the therapeutic effects of the drug on a medical condition; opioid manufacturers have that burden as well as, now, demonstrating the effectiveness of preventing abuse of the drug. The draft guidance lays out a three-step process for formulation development: in vitro manipulation and extraction (to see how easily it is to get at the opioid); pharmacokinetic studies; and clinical abuse potential studies. The latter category seems to be especially challenging: FDA wants developers to engage with “opioid-experienced abusers who have experience with the particular route of abuse being studied,” but who “should not be physically dependent and should not be currently seeking or participating in treatment for drug abuse.” In other words, ex-users who will now be ingesting (via inhalation, intravenous or swallowing) the very drug that made them an abuser.
A fourth category, postmarketing studies, will require developers to go out into the drug-abusing population, via public-health studies and other routes, to assess how well the deterrence is working on the street, including “a population of known drug abusers.” If a developer can make it this far, the finish line is a label claim that ranges from simply noting that the drug “is formulated with physicochemical barriers to abuse,” to a label claim that the drug “has demonstrated reduced abuse in the community.”
While Margaret Hamburg, FDA Commissioner, noted that “This draft guidance is an important part of a larger effort by FDA aimed at preventing prescription drug abuse and misuse,” a lot of the current enforcement action is with DEA, which has gone after local pharmacies, and regional and national distributors to tighten the distribution of opioids and other controlled substances. Meanwhile, thousands of deaths continue to occur annually due to abuse.