The FDA yesterday issued proposed rules or “draft guidance” designed to encourage drug developers to manufacture abuse-resistant opioid pain medicines.
“Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling” will apply to biopharmas companies planning to launch new formulations of opioid products. It contains FDA’s perspective on what studies drug makers should conduct to show the agency their medications are abuse-resistant, how those studies will be evaluated, and what labeling claims may be allowed based on study results.
FDA said drugmakers should present data from each of three categories of premarketing studies—in vitro manipulation and extraction studies, pharmacokinetic studies, and clinical abuse potential studies—as well as from postmarketing studies showing how a potentially abuse-deterrent formulation results in “a significant decrease in population-based and use-based estimates of abuse” compared to abuse estimates for non-abuse-deterrent formulations.
Labels of abuse-resistant opioid drugs, FDA continued, should describe the product’s specific abuse- deterrent properties as well as specific routes of abuse the product is designed to deter. The agency promised to “take a flexible, adaptive approach” to evaluating and labeling treatments with the potential for opioid abuse.
“Our goal here is to encourage the development of abuse-deterrent formulations that work to reduce abuse in the real world. And the intent of the guidance is to find a way to incentivize that, and to encourage the development of that science,” Douglas Throckmorton, M.D., deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, said yesterday during a conference call for reporters on the proposed regulations.
FDA opened a 60-day comment period for the draft guidance, with a public hearing to follow. The date of that hearing has yet to be set, Dr. Throckmorton said.
The draft guidance comes in response to a provision of the FDA Safety & Innovation Act (FDASIA) as well as requests from the Office of National Drug Control Policy (ONDCP). The agency said the proposed rules were part of a multi-agency response to pain drug abuse, which according to FDA resulted in about 15,600 deaths and nearly 425,000 emergency-room visits involving opioid medications.
“Abuse and misuse of these products is a serious and growing public health problem, and is a priority for the FDA,” Dr. Throckmorton said.
FDA released the draft guidance about a month after guidance comes one month after an advisory committee voted against recommending agency approval of the Zogenix opioid drug candidate Zohydro, citing the drug’s lack of abuse resistance, and resulting potential for abuse. But the Anesthetic and Analgesic Drug Products Advisory Committee balanced its decision by advising that FDA not make its decision until it adopts a rule requiring abuse resistance formulations of pain drugs. Zogenix has said it is developing an abuse-resistant version of Zohydro.
A few other drug developers are marketing abuse-resistant formulations of their pain drugs—including Purdue Pharma, maker of OxyContin (oxycodone), and Endo Pharmaceuticals, maker of Opana (oxymorphone). However, FDA-approved generic versions of Opana that lack tamper resistance were approved before the branded drug’s June 2012 reintroduction with a crush-resistant formulation. Generic versions of Opana ER 7.5 mg and 15 mg are available from Actavis, which will join several companies expected to launch additional generic versions in 2013 including Impax, Sandoz, Teva, Watson, Roxane, and Ranbaxy.
Questioned why FDA is asking branded-drug makers to switch to abuse-resistant formulations and not makers of generic Opana or other generic drugs, Dr. Throckmorton said he could not comment on agency conversations with the generic developers involved.
While the draft guidance does not apply to generic drugmakers, FDA says it is evaluating several citizen petitions requesting action on abuse resistance in generic drugs. "What we do about the generics is something we have not yet determined," Dr. Throckmorton added.