WASHINGTON — The FDA needs to put a moratorium on approval of opioid drugs until it finishes developing a framework for such approvals, Public Citizen and the chairman of an FDA advisory committee said Thursday.
“The agency has been given every opportunity to act in the interest of the American public,” said Raeford Brown Jr., MD, chairman of FDA’s Anesthetic and Analgesic Drug Products Advisory Committee, on a phone call with reporters. “At the direction of the former commissioner, Robert Califf, MD, the FDA spent many tax dollars to engage the National Academies [of Science, Engineering, and Medicine] in an effort to define the agency’s responsibility for the current and ongoing problems with prescription opioids and establish a new way forward in the regulatory process consistent with the existing statutory authority provided by Congress.”
“This process was finished more than 1½ years ago with a powerful report accepted by the current commissioner that’s been supported by the scientific and health community,” Brown continued. “However, the agency has yet to respond to substantial changes suggested by the academies. Those of us that study the activities of the FDA have yet to observe behaviors indicating the agency is prepared to accept responsibility for the opioid crisis and substantially change the regulatory framework.”
“As an important contributor to the current opioid crisis because of its poor record, the FDA can no longer be trusted to approve opioids,” said Sidney Wolfe, MD, founder of and senior adviser to Public Citizen’s Health Research Group, which, along with Brown, filed a petition formally asking for a moratorium on opioid drug approvals.
“A moratorium will force the FDA and its advisers to actually design and implement the regulatory framework recommended almost 2 years ago by the National Academies, but [which is] still dangerously unfinished. To continue approving opioids such as Opana ER [oxymorphone] and more recently, Dsuvia [sufentanil] before developing this framework for safer opioid regulations is to guarantee further opioid disasters and FDA culpability.”
In particular, Wolfe said, “in 2011, the agency approved reformulated Opana ER despite previous evidence that it could be easily manipulated to facilitate intravenous abuse … the FDA’s unsupportable claim at the time of approval that this evidence of possible increased intravenous use did not constitute a safety problem became its excuse for not having any pre-approval safety advisory committee meeting.”
“The FDA then took more than 6 years to remove the medication from the market despite rapidly mounting evidence that the predicted intravenous abuse of the drug was leading to a public health emergency,” he said.
Wolfe, a former member of the FDA’s Drug Safety and Risk Management Advisory Committee, also called for replacing Janet Woodcock, MD, the current director of the agency’s Center for Drug Evaluation and Research. “I think getting a new director of drugs at [the] FDA would be an important step while the moratorium is on to ensure the moratorium is usefully spent developing this now-delayed regulatory framework for opioids,” he said.
The petition filed Thursday notes that “in the past two decades … the FDA has approved new opioids or reformulations of existing opioids when previously known risks of the drugs exceeded their known benefits. These approvals violated the FDA’s current drug approval requirements for ensuring safety and effectiveness and deviated from the principles articulated in the FDA’s requested assessment of its opioid approval process by the [National Academies], which concluded that the FDA had failed to adequately ‘incorporate public health considerations into opioid-related regulatory decisions.'”
“The FDA’s continued approval of new potent opioids, which are known to threaten the public health, without first significantly improving the review process by creating and finalizing an opioid regulatory framework recommended by the National Academies represents a clear and present continuing danger to the health and safety of people in this country,” the petition said.
“Until improvements are made, the FDA does not have a framework to effectively evaluate [new drug applications] for new opioids and new opioid formulations to determine whether the legal standards for establishing safety and effectiveness are met. Thus, an immediate moratorium on opioid approvals is needed urgently.”
In its 2017 report, the National Academies made a variety of recommendations to the FDA, including that the agency consider the following factors when weighing an approval decision:
- Benefits and risks to individual patients, including pain relief, functional improvement, the impact of off-label use, incident opioid use disorder (OUD), respiratory depression, and death
- Benefits and risks to members of a patient’s household, as well as community health and welfare, such as effects on family well-being, crime, and unemployment
- Effects on the overall market for legal opioids and, to the extent possible, impacts on illicit opioid markets
- Risks associated with existing and potential levels of diversion of all prescription opioids
- Risks associated with the transition to illicit opioids (e.g., heroin), including unsafe routes of administration, injection-related harms (e.g., HIV and hepatitis C virus), and OUD
- Specific subpopulations or geographic areas that may present distinct benefit-risk profiles
After the agency acknowledges receiving the petition, “the next step is a pro forma response in 6 months saying ‘We’re working on this,'” Wolfe said. If the agency doesn’t act on the petition, Wolfe said his group may sue under the Administrative Procedures Act. “In this case, we are not going to wait a very long time because this is a national crisis.”
Public Citizen is also “going to try and enlist [help from] members of Congress,” he said. “I think there’s a lot of interest, particularly now that the House has leadership more likely to go against the industry … There’s going to be lot of action parallel with [us] at the same time, hopefully increasing the chances for a moratorium.”
Asked to comment on the petition, an agency spokeswoman said in an email that the FDA “is reviewing the petition and will respond directly to the petitioners.” She referred a reporter to FDA Commissioner Scott Gottlieb, MD’s statement on the Dsuvia approval and a broader statement on the opioid epidemic for more information.