US Food and Drug Administration (FDA) Commissioner Margaret Hamburg, writing in a letter to congressional legislators, has determined that the agency has the regulatory authority to require generic medications containing opioids to have abuse-deterrent qualities, providing a potentially significant boost to branded opioid manufacturers who for months have argued that their potential generic competitors should not be allowed to market first-generation non-abuse-deterrent opioid products.
"[The Department of Health and Human Services] and FDA share your concerns, and those of your constituents, regarding prescription drug abuse, including the abuse of opioid analgesics," Hamburg wrote in her letter to Fred Upton, chairman of the Committee on Energy and Commerce, the congressional committee primarily in charge of overseeing FDA.
"As part of our ongoing mission to protect public health, FDA has concluded that if FDA determines that a formulation of a product significantly deters abuse, we have legal authority under the drug approval and drug safety provisions of the Federal Food, Drug and Cosmetic Act to require generic versions of that product to have abuse-deterrent formulations as well."
An Issue of Safety-or Dominance
Branded opioid manufacturers have been arguing in recent months that non-abuse-deterrent opioid products would represent a risk to public health, and that FDA should prevent them from being marketed until they are have equivalent abuse-deterrent qualities to current-generation opioid products. The move is seen by some critics as an attempt to delay the onset of generic competition, but by others as being in support of public safety. Approximately 15,000 deaths are attributable to opioid overdoses each year, reports The New York Times.
FDA has been coy on the subject of whether it will explicitly require generic manufacturers to have abuse-deterrent qualities. In a press call on 9 January, FDA's Douglas Throckmorton, deputy director of the Center of Drug Evaluation and Research (CDER) said, "What we're going to do about the generics is something that we have not yet determined."
Hamburg confirmed this in her 8 January 2013 letter to Upton, saying the agency is still "actively reviewing whether it can and should seek to remove or refuse to approve opioid drug products not formulated to deter abuse in certain circumstances."
Litmus Test: Do Qualities Deter Abuse?
As part of the agency's review, Hamburg said regulators were now reviewing the evidence to determine if the newer 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 responded to a question of Upton's in which he implied that FDA should withdraw approval for older, non-abuse-deterrent formulations of currently-marketed opioid products, and that the products could be seen as an "imminent hazard to the public health" under Section 505(e) of the FD&C Act. Hamburg 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), the agency had 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.
Hamburg's lack of elaboration on the answer could be taken by some to mean that it would not be the agency's preferred method of action.
The letter also establishes that it expects to be able to provide incentives for companies willing to submit applications containing medicines with abuse-deterrent qualities.
First, Hamburg noted that products with abuse-deterrent formulations would likely be given fast-track or priority review status to "encourage the development and to speed the approval process of such products," providing a strong incentive for companies to include abuse-deterrent qualities in their products. Fast-track and priority review processes can significantly speed up review times, generally aiming for an approval decision within six months. This can sometimes halve the amount of time taken to receive an approval decision-a huge benefit for generic products looking to establish a foothold in a market no longer dominated by a single competitor.
Hamburg also noted a recent draft guidance issued by the agency that it says incentivizes the development of abuse-deterrent opioid products and may provide a blueprint for product development going forward. The guidance calls on industry to study the effectiveness and safety of their products in high-risk populations, and rewards them by being able to market their products as being explicitly "abuse-deterrent."