As pressure continues to mount on the US Food and Drug Administration (FDA) over its October 2013 decision to approve a controversial pure hydrocodone painkiller known as Zohydro ER (hydrocodone bitartrate), several legislators are trying to convince the government itself to launch an investigation into the matter.
Background: What is Zohydro?
FDA approved Zohydro in 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.
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.
The drug's lack of abuse-deterrent qualities has made it a lightning rod for critics, who contend that its existence will exacerbate rates of drug abuse.
Legislators as Critics
Among those critics are several prominent US senators, who have launched a steadily escalating campaign against the drug and FDA for having approved it.
As Regulatory Focus has previously covered, Senate Minority Leader Mitch McConnell sent a letter to FDA in February 2014 demanding to know why the agency had approved Zohydro.
Then, in early March 2014, Sen. Charles Schumer (D-NY) launched a new strategy: Lobby the US Department of Health and Human Services (DHHS), FDA's parent agency, to overturn the Zohydro decision. DHHS has only once before in its entire history overturned an FDA decision, which occurred in 2011. A week later, Sen. Joe Manchin (D-WV) signed on to that strategy, firing off his own letter to DHHS calling for the removal of Zohydro.
A week later, Manchin introduced the Act to Ban Zohydro, which specifically calls for "withdrawal of approval of drug Zohydro ER" no later than 45 days after the passage of the Act, and for FDA not to approve "any application under section 505 of the Federal Food, Drug and Cosmetic Act (FD&C Act) for pure hydrocodone bitartrate extended-release capsules" lacking abuse-deterrent qualities.
On 13 March 2014, a bipartisan group of 13 House legislators introduced identical companion legislation-also known as the Act to Ban Zohydro-intended to force the drug off the market within 45 days and to prevent future non-abuse-deterrent versions of the drug from reaching the market.
The legislative interference has led to concerns that it could set a dangerous precedent for future approvals, and that legislators would be more open to overturning future controversial drug approvals, thereby diluting FDA's power as a regulator.
Legislators: Investigate FDA Participation in Meetings
Now a bipartisan group of legislators are taking yet another tactic: Get the government to investigate FDA's approval.
In a letter send to DHHS' Office of the Inspector General (OIG), Reps. Rosa DeLauro (D-CT), Harold Rogers (R-KY) and Stephen Lynch (D-MA) said they wanted OIG to "examine the relationship between industry and the FDA in facilitating the approval of Zohydro at the expense of public health and consumer safety."
"FDA Advisory Committees seldom vote against approval, and such overwhelming opposition is even rarer," the representatives wrote in the letter, addressed to OIG Inspector General Daniel Levinson.
FDA is not bound to follow the advice of its advisory committees, but often does-about 75% of the time, depending on the year.
The letter also notes FDA's recent actions to more tightly schedule hydrocodone under the Controlled Substances Act (CSA), calling it perplexing that FDA would on one hand take actions intended to reduce the supply and availability of hydrocodone, and on the other approve a drug without abuse-deterrent qualities.
The approval, they said, "raises several questions," including the "dubious ethical involvement of corporate pharmaceutical interests in the regulatory process," referring to FDA regulators' participation in a small invitation-only conference where some companies paid as much as $35,000 to attend.
Zogenix, the sponsor of Zohydro, has maintained that it was not among the companies in attendance at that conference, though MedPage Today reports that Zohydro's initial manufacturer, Elan-now Alkermes-was in attendance.
The letter nevertheless calls for OIG to investigate FDA involvement at the conference, and to determine if it was improperly influenced and led to a "less scrutinized and less transparent drug approval process for Zohydro ER."
Other Meetings Suspect as Well?
The letter also calls into question FDA's attendance at many association conferences, such as the Food, Drug and Law Institute (FDLI). Those conferences may allow attendees to "influence FDA officials," but are "frequently unaffordable to any stakeholders other than pharmaceutical and device companies," the letter contends.
Full Disclosure: RAPS, the parent organization of Regulatory Focus, also puts on conferences and events at which FDA attendance is frequent.
"Ensuring that patients and consumers are protected against dubious ethical involvement of corporate pharmaceutical interests in the regulatory process helps to ensure public health is protected," they continued. "This requires transparency. Accordingly, this matter requires closer inspection."
The legislators request a response by OIG by 15 April 2014.
Letter to OIG