A senator has become the second legislator in two weeks to call on the secretary of the Department of Health and Human Services (DHHS) to exercise an authority-one used only once in the agency's history-to overturn a recent regulatory decision by the US Food and Drug Administration (FDA).

Background: Zohydro

That regulatory decision was with regard to Zohydro ER (hydrocodone bitartrate), a pure hydrocodone pill approved by FDA on 25 October 2013. The approval decision was seen by many as surprising, as it followed an FDA advisory committee meeting at which a majority of the committee members voted against approving the drug, citing its potential for abuse. The drug, unlike most hydrocodone-based products on the market, lacks abuse-deterrent characteristics, making it easier to abuse.

The drug, however, is indicated for those who experience severe pain and require around-the-clock treatment. Advocates for the drug have cited the need for a hydrocodone product without acetaminophen, which can cause toxicity in high doses.

The product's manufacturer, Zogenix, said in a statement that the product would especially help patients avoid liver injury, which can be caused by high-dose long-term use of acetaminophen.

Background: Pressure on Zohydro

But despite the drug's Schedule II status under the Controlled Substances Act (CSA) and participation in a class-wide opioid Risk Evaluation and Mitigation Strategies (REMS) plan, many legislators have expressed their displeasure at the drug's approval.

In February 2014, Senate Minority Leader Mitch McConnell and several other top Republicans sent a letter to FDA demanding to know why the agency had approved the drug.

"This decision contradicts FDA's own advisory panel, and could undermine the important measures taken by FDA, lawmakers and state attorneys general to curb prescription drug abuse across the country unless accompanied by appropriate safeguards and due consideration for the potential for abuse," they wrote.

Several weeks later, Sens. Joe Manchin (D-WV) and David Vitter (R-LA) followed suit, accusing FDA of being improperly influenced by participation in a small invitation-only conference where some companies paid as much as $35,000 to attend.

"We are deeply troubled by allegations that the FDA gave manufacturers of prescription drugs the opportunity to pay thousands of dollars to the University of Rochester Medical Center (URMC) for the privilege to attend private meetings with FDA officials," they wrote.

Those meetings, they said, may well have influenced FDA's decision to approve Zohydro and delay rescheduling hydrocodone as a Schedule II drug.

New Regulatory Strategy: Ignore FDA

Then, in early March 2014, Sen. Charles Schumer (D-NY) unveiled a surprising strategy: Stop worrying about FDA, and instead lobby DHHS Secretary Kathleen Sebelius to overturn the Zohydro decision.

As Regulatory Focus explained last week, such a move has only occurred once in FDA history. In 2011, Sebelius personally overturned FDA's decision to approve Teva Women's Health's application for Plan B One-Step (levonorgestrel), which the company was seeking for over-the-counter status.

But with that precedent-setting decision on the books, Schumer pressed DHHS to again use its authority, this time to overturn the approval of Zohydro.

"It is inexcusable that a product with more potency and without abuse deterrent technologies has been approved for production," Schumer wrote in a letter to Sebelius.

"I urge you to override the FDA's approval of Zohydro ER and work quickly to stop it from being sold to consumers," he concluded. "It is essential that we stop yet another dangerous drug from playing a role in our country's national drug epidemic, and that we also begin to incorporate abuse-deterrent technologies into all dangerous opioids as new drugs are introduced to the market."

Manchin Follows Schumer

That strategy is now getting a co-sponsor in the Senate. On 10 March 2014, Sen. Manchin again sent a letter, this time ignoring FDA-the usual recipient for letters regarding drug approvals-and instead focusing entirely on DHHS.

"I write to respectfully request that you overturn the Federal Drug Administration's recent approval of Zohydro Extended Release (ER), a powerful and dangerous opioid drug product with a high potential for abuse," Manchin wrote in his letter to Sebelius.

FDA had approved the drug for "inexplicable reasons," he added, and the drug-set to launch in March 2014-"must be stopped before … [it] is sold to the public."

Earlier letters to FDA had fallen on "deaf ears," he added.

Regulatory Uncertainty

The letters by Manchin and Schumer raise regulatory uncertainty for more companies in the future. If Sebelius relents and agrees to overturn the drug's approval decision, conceivably any drug product that is politically unpopular could be subject to political pressure to overturn its approval.

And more alarming still, it raises the possibility that a new DHHS secretary could unilaterally decide to revoke the approvals of other drugs-the abortifacient drug Mifepristone (Ru 486) for example.

In other words: We may soon be approaching a future in which FDA is no longer the last word on regulatory approvals.

 

Manchin letter