Regulatory Focus™ > News Articles > Policy on Generic Abuse-Deterrent Opioids Coming Soon, Will Adopt Case-by-Case Approach

Policy on Generic Abuse-Deterrent Opioids Coming Soon, Will Adopt Case-by-Case Approach

Posted 03 April 2013 | By Alexander Gaffney, RAC

US Food and Drug Administration (FDA) Commissioner Margaret Hamburg told an audience of opioid abuse advocates that the agency is tantalizingly close to finalizing a policy on requiring abuse-deterrent qualities for generic opioids, and that the policy is likely to take a case-by-case approach rather than the one-size-fits-all approach favored by some critics.


Speaking this week at the National Rx Drug Abuse Summit, Hamburg told participants that her agency recognizes both the promise and perils of prescription opioid medications, and has been working diligently through numerous paths to target imprudent and dangerous use of the drugs without cutting off access to those who depend on the drugs.

"FDA is certainly striving to do its part," Hamburg explained. "Our multi-pronged approach is targeted at critical points in the lifecycle of an opioid product."

FDA has indeed been busy, particularly in the latter months of 2012. In July, it instituted its first-ever class-wide Risk Evaluation and Mitigation Strategy (REMS) policy for extended release and long-acting opioid products, mandating that all such products include educational materials at the point of prescribing. Later that same month, the agency announced a crackdown on manufacturers of unapproved oxycodone products, ordering them to cease marketing immediately.

In December 2012, FDA went on to propose a new prescribing paradigm for opioids, saying it's interested in exploring ways to reduce the use of opioid products for certain types of pain while preserving it for others.

Then, in January 2013, FDA came out with a new guidance aimed at incentivizing abuse-deterrent studies for opioid products.

Sticking Points

But the agency has drawn most fire regarding pending changes that could see generic versions of existing, non-abuse-resistant opioids brought onto the market.

The problem is effectively a double-edged sword. On one side, many are concerned that if generic versions come to market, more people will have access to non-abuse-resistant opioids, thereby erasing much of the hard work done by manufacturers and public health and safety officials. On the other hand, some have maintained that attempts to make all generic opioid manufacturers have abuse-deterrent qualities is simply a ploy to delay competition, and might actually lead to shifting patterns of abuse.

For its part, FDA has been trying to walk the fine line between determining what constitutes the full measure of the public good. In late January 2013, it said it needed more time to determine whether all opioids should be crush-resistant, and denied a Citizen Petition by Endo Pharmaceuticals, the manufacturer of Opana ER.

"Throughout this process, we must strike a balance between the risks associated with misuse, abuse and addiction and the potential benefits of these products in helping patients who have pain," Hamburg said in her remarks. "All available drugs - even aspirin - have their challenges, but opioid drugs require our special attention and concern."

Prior Hints at a Policy

But some hints have emerged that Hamburg may be considering requiring most manufacturers to adopt abuse-deterrent qualities.

In a letter to legislators in January 2013, Hamburg said regulators were reviewing the evidence to determine if the newer "abuse-deterrent" formulations "actually deter abuse."

If the newer formulations are found to deter abuse, the agency will have the legal authority to require generic versions of the products to have those qualities as well, though Hamburg stopped short of saying that FDA definitely would exercise that authority.

Hamburg also explained that while FDA does indeed have the authority to unilaterally withdraw the approval of a drug from the market (so long as it provides the applicant with notice and an opportunity for a hearing) if it finds it to be an "imminent hazard to the public health," the agency has only used that authority once, in 1977, to withdraw all products containing phenformin hydrochloride. That product was associated with the high risk of lactic acidosis, a highly deadly condition in which lactic acid builds up in the blood stream faster than the body can remove it.

New Developments: A Case-by-Case Approach

In her speech to the National Rx Drug Abuse Summit, Hamburg reiterated this point, saying that FDA has "concluded that, if FDA finds a new formulation to be abuse deterrent, then the Agency has the legal authority under the Food, Drug and Cosmetic Act to require that generic versions of that product have abuse-deterrent formulations as well. In addition, under certain circumstances, we believe that we would have the authority to refrain from approving non-abuse-deterrent formulations of that drug and to initiate procedures to withdraw non-abuse-deterrent versions already on the market.

Advocates of a comprehensive ban on non-abuse-deterrent generics, however, are likely to be disappointed. Hamburg said her agency has already found that abuse-deterrent qualities are "not straightforward," and that the agency is accordingly approaching the issue from a case-by-case basis.

"FDA's scientific staff is actively reviewing the data relating to specific opioid products," Hamburg said, adding that she had hoped to be able to announce a formal policy on the day of the meeting. "Unfortunately, we're not ready to do that, but I can report that we expect to do so soon," she said.

Interaction with DEA

Hamburg also conceded that her agency was in the midst of an "impassioned, sometimes heated, debate" between patients, families, law enforcement, educators, companies and the medical community at large.

And one other group is involved in that debate in a prominent way: the Drug Enforcement Administration (DEA), which recently penned a letter to FDA indicating its desire to see oxycodone products more tightly regulated.

"The DEA is concerned about the potential public health risks resulting from abuse of opioid drug products," it wrote. "Additional regulatory measures are necessary for opioid formulations to adequately safeguard the American public."

Those measures would include "restrictions on prescribing, marketing practices and clinical indications for these opioid products.

"The clinical use of opioid analgesics must be accompanied by appropriate measures to minimize the adverse health impact associated with the diversion and abuse of these products," it continued. "The DEA hopes that FDA will implement suitable measures, such as labeling revisions, to help mitigate the adverse impact on the public health resulting from abuse of these products."

In her speech, Hamburg acknowledged this letter, saying FDA is "currently working on DEA's request for a scientific and medical evaluation and scheduling recommendation on drugs containing hydrocodone, either combined with other analgesics such as acetaminophen or for cough suppression in combination with other cough-cold substances."

"We recently convened a two-day advisory committee meeting with experts on this subject and are reviewing their advice as we prepare our recommendations to DEA," she said.

And, Hamburg added, FDA is approaching this evidence from a "targeted science-based, multi-pronged approach that addresses misuse, abuse and addiction at critical points in the lifecycle of an opioid product," of which abuse-deterrent properties are a part.

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