The US bio pharmaceutical industry's two largest trade groups are calling on the US Food and Drug Administration (FDA) not to approve—or to revoke approval for—generic equivalents of older, non-abuse-resistant painkillers if a drug manufacturer has since made improvements to a drug to make it harder to abuse.
Background
FDA's regulation of opioid painkillers has a long and complicated history. In recent years, FDA's regulation of opioids had attracted a significant amount of critical attention from legislators as the death toll associated with painkiller abuse has skyrocketed.
The agency has taken several actions since 2012 that have attracted significant attention:
Its October 2013 approval of the pure hydrocodone painkiller Zohydro, which prompted concern from legislators that the approval of the drug was tone-deaf and ignored its potential to cause overdoses. The agency has since approved an abuse-deterrent version of a similar drug, Hysingla, but has not removed Zohydro from the market.
A January 2013 guidance document calling on manufacturers to provide data indicating their opioid products are resistant to abuse by patients.
FDA's October 2013 recommendation that the Drug Enforcement Administration (DEA) regulate all hydrocodone combination products as Schedule II drugs under federal law, thereby making them more difficult to obtain in large quantities.
FDA's September 2013 policy change which requires safety labeling changes and postmarket studies for extended release (ER) and long-acting (LA) opioid analgesic products.
FDA's July 2012 launch of a class-wide Risk Evaluation and Mitigation Strategies (REMS) policy for opioid products, meant to train and educate prescribers on the safety use of opioids.
To date, FDA's strategy seems to be focused on two competing factors: Ensuring that patients who rely on painkillers to manage their severe and ongoing pain have ready access to the drugs they need; and ensuring that those same painkillers are not so easily available as to lead to rampant abuse.
The Problem with Generics
But even as FDA has grappled with how to best regulate new painkillers, it has also struggled to form a coherent policy regarding generic painkillers.
The problem is this: When FDA approves an opioid, often times the first version of that drug is a non-abuse-resistant version. Many times manufacturers then release subsequent reformulations which make the drug harder to abuse, and also serve the increase the amount of time a manufacturer can market a drug without competition. In many cases, the manufacturer will then remove the first version of the drug from the market, leaving only the new, abuse-deterrent version of the drug available to consumers.
This leaves FDA in a case-by-case conundrum. Because the non-abuse-resistant version of the drug was the first on the market, it is almost always the first to have its patents or marketing exclusivity expire, leaving it vulnerable to generic competition. Even if the drug has been withdrawn from the market, a company can file a petition with FDA for the agency to find that the drug was "not withdrawn from the market for reasons of safety or efficacy." If FDA finds the drug was not withdrawn for either reason, the generic manufacturer would then be permitted to file an application with FDA for approval of the generic version of the non-abuse-deterrent drug.
That case-by-case approach has led to some surprising decisions. For example, in June 2013 FDA said it would allow non-abuse-deterrent versions of the painkiller Opana ER to be sold. FDA said it could find no convincing proof that the subsequent, supposedly more abuse-deterrent version of the drug was actually any safer or harder to abuse than the original formulation.
As explained by Janet Woodcock in November 2014, FDA's director of the Center for Drug Evaluation and Research (CDER), the problem is that abuse-deterrent technologies are still very much in their "infancy," and that the mere presence of such a technology should not automatically preclude generic competition.
On the other hand, FDA has shown it is willing to say no to non-abuse-resistant copies of painkillers. In April 2013, the agency said it would not approve non-abuse-resistant generic versions of Purdue's Oxycontin, which it said had been removed from the market for reasons of safety or efficacy. FDA formally withdrew the drug application for the original formulation of Oxycontin several months later in August 2013.
In the meantime, FDA's varying decisions have attracted the attention of legislators, who in May 2014 asked FDA Commissioner Margaret Hamburg to explain why FDA has not yet finalized its January 2013 guidance document on abuse deterrence.
"It is important to ensure that the FDA does not apply a less stringent abuse standard for generic products," the four legislators wrote.
PhRMA and BIO: No Deterrence, No Approval
The legislators' stance is nearly identical to sentiments expressed last week to FDA by the trade groups PhRMA and BIO, who wrote to FDA in support of stricter standards of approval for generic non-abuse-resistant opioids.
"When an innovator has developed, and FDA has approved, such a [abuse-deterrent] formulation, FDA should not approve a generic formulation of the medicine that does not incorporate comparable abuse deterrence," the trade groups wrote.
The issue, they said in their 7 January 2015 letter to FDA, is as much about incentives for innovation as it is about promoting patient safety.
"We believe that permitting the approval of generic products that lack comparable abuse deterrence not only undermines the incentive for innovative biopharmaceutical companies to invest in important new abuse deterrent technologies, but more importantly, fails to mitigate a public and societal health risk," they wrote. In other words, if a company invests a significant amount of time and money into developing a drug which is safer than the original, why should FDA discount that investment and allow the harm to be perpetuated?
Both groups said FDA should exercise its authority to "remove from the market non-abuse-deterrent generic formulations of the same drug." Interestingly, the group mentions only generic drugs in that statement. It does not, for example, call for the removal of branded versions containing the same active ingredient without similar abuse-deterrent qualities.
"Under its existing regulatory authority, FDA has the ability to remove generic formulations that lack abuse deterrent characteristics from the market, when the additional relative safety of a new formulation of a medication with abuse deterrent properties is available," PhRMA and BIO continued. "We encourage FDA to exercise its authority to continue to protect the public health. FDA should incentivize the development of abuse deterrent formulations, which is in the best interest of patients."
PhRMA/Bio Letter to FDA
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