The FDA’s decision to not accept or approve any ANDAs (abbreviated new drug applications) for generics that rely upon the approval of original OxyContin means the generic companies will have to invest considerably more money in abuse-deterrent formulations.
Here are the latest labels for Purdue and Endo Pharmaceuticals’ oxycodone drugs:
The agency says that any generic companies will now have to make it more difficult to crush, break, or dissolve OxyContin generics, as well as form a “viscous hydrogel” so the drug cannot be easily prepared for injection.
Although the FDA has yet to detail how companies should implement the abuse-deterrent technology, Dr. Stephen Brown -- R&D director of Encap Drug Delievery, a subsidiary of Capsugel -- told us that “there are technical in vitro tests we’ve developed in house to test how easy it is to grind and powder formulations and extract with solvents.”
The methods may vary slightly between companies, but there are “fairly standard techniques” to ensure abuse deterrence, especially when testing formulations against an innovator’s non-abuse-deterrent product, Dr. Brown said. And the FDA understands the methodologies these companies are using and can ensure the data is accurate, he said.
All of the drugs have used GRAS (generally regarded as safe) excipients that “have been around for some time” but the right formulation depends on the drug, Dr. Brown added.
Recent draft guidance, however, does provide some background on what companies should do to ensure their products are abuse deterrent.
“The guidance is a step, but I anticipate we and others will be teasing this out with the FDA in the days ahead,” said a Senate aide who requested anonymity because of his proximity to the decision making.
Teva Pharmaceutical Industries, Impax Laboratories and Covidien’s generics division Mallinckrodt all were seeking approval of their generic versions of OxyContin when the FDA’s decision came out late Tuesday. But none of them have commented on whether they would adopt the expensive abuse deterrent formulations.
James Heins, a spokesman for Purdue Pharma, told us the company’s abuse-deterrent technology took almost nine years to develop and generic manufacturers “should be willing to develop their own abuse-deterrence technologies and develop products accordingly, or get a license to use the abuse-deterrence technology from any of the companies that have already invested to develop such technology.”
In terms of the types of testing involved, Purdue “completed laboratory manipulation and extraction testing, pharmacokinetic and abuse ‘liking’ studies for the reformulation of OxyContin prior to its approval in April 2010,” Heins said. “Purdue has also undertaken extensive epidemiologic studies to evaluate the effect of the reformulated OxyContin tablets on misuse and abuse and related consequences (e.g. addiction, overdose and death) in real-world conditions. We have submitted data from these ongoing studies to the FDA.”
Market for Abuse Deterrent Generics
Two opioid analgesics approved with abuse‐deterrent language in their FPI (full prescribing information) include Pfizer and Acura’s Oxecta and Pfizer subsidiary King Pharmaceuticals’ Embeda.
Despite the FDA recognizing the importance of these formulations, neither drug has been able to capitalize on the market as less-expensive and non-abuse-deterrent formulations of interchangeable drugs have dominated the market, according to Purdue.
Purdue estimates that both drugs make up less than 1% of the opioid market.
Congressional Action
The FDA’s decision follows a strong push in both the House and Senate to require the abuse deterrent properties for generic versions of the opioids.
On Monday, US Sens. Tom Coburn (R-OK) and Charles Schumer (D-NY) introduced a resolution calling on the FDA to “encourage the use of abuse-deterrent formulations of drugs.” Sen. Lamar Alexander (R-TN) also signed onto the resolution on Tuesday, according to a Senate aide.
Sen. Coburn also filed an amendment to this year’s budget that would define abuse-deterrent formulations in statute and require generic prescription opioid drugs to have abuse-deterrent properties.
“To account for future innovations in abuse-deterrent formulations, the amendment allows the FDA to supersede the definition of abuse-deterrence at a later date through a transparent, formal rulemaking process requiring public comment,” Coburn’s office said in a statement.
In addition, Rep. Michael G. Grimm (R-NY) called on the FDA on Tuesday to not approve generic opioids.
“At this time, brand-name opioids contain tamper resistant properties that prevent them from being crushed, snorted, or injected, or otherwise abused. The generics do not. With 800 million generic doses scheduled to hit the market this Tuesday, it is imperative that the FDA enforce that they contain abuse deterrent properties,” Rep. Grimm said.
In addition, Sen. Coburn and Rep. Fred Upton (D-MI) sent a letter to FDA Commissioner Margaret Hamburg last month on the issue.