US FDA May Seek Legal Authority To Require Superiority Tests For Future Opioids
Executive Summary
Commissioner Califf testifies at budget appropriations hearing that the agency may ask Congress to give it authority to require a new opioid drug application to show superiority to opioids on the market.
The US Food and Drug Administration may go beyond recommending that sponsors show that a new opioid product has an advantage over marketed drugs to actually requiring superiority data.
FDA Commissioner Robert Califf commented at a 28 April Senate Appropriations Subcommittee hearing that the agency may ask Congress for the legal authority to impose such a requirement.
Responding to a question about the FDA’s plans to address opioid safety, Califf said there are a couple of areas “where we’re probably going to come back to you if there’s concurrence within HHS and say that we need some new legal authority.”
For example, he said, the agency doesn’t have the legal authority right now to require that a new drug application show the product is superior to drugs already on the market. “I think that’s something that I would like to see happen that may require something from Congress to institute,” he stated.
Califf said the legal comparative standard is comparing a product to placebo or nothing. But he said opioids “don’t work like other drugs.”
Sen. Mike Braun, R-IN, said most members of the subcommittee would find this additional authority and subsequent rulemaking to be warranted.
Opioids Are Different
Califf was testifying before the Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies on the agency’s fiscal year 2023 budget request. His comments indicate that the agency would like to surpass the comparative effectiveness standard put forward in its 2019 draft guidance on opioid analgesic drugs.
In that document, the FDA said it would consider a proposed product’s benefit-risk balance relative to approved analgesics, and evaluate whether it provides any advantages over existing pain therapeutics. (Also see "New Opioids May Need Comparative Effectiveness Data For Approval" - Pink Sheet, 20 Jun, 2019.)
Before the draft guidance was released, former FDA Commissioner Scott Gottlieb advocated this approach at the subcommittee’s hearing on the agency’s proposed FY 2020 budget. He said the FDA needs to treat opioids “as a class differently than we evaluate other drug classes.” (Also see "FDA Finalizes Comparative Safety, Efficacy Requirement For New Opioids" - Pink Sheet, 5 Apr, 2019.)
Gottlieb also noted in a statement on FDA’s 2019 opioid policy that the comparative framework could include “seeking revisions to statutory authorities to allow us to change the weight we give to meaningful therapeutic differentiation for proposed new opioids, including relative safety or effectiveness advantages over existing treatments.”
Last year, the agency signaled its intent to weigh broader public health considerations in certain benefit-risk decisions, an approach that would have a significant impact on opioid products, though the draft guidance was not limited to any particular class. (Also see "Beyond Individual Patients: FDA Emphasizes Public Health Role In Certain Benefit-Risk Decisions" - Pink Sheet, 30 Sep, 2021.)
Policies In The Works
Braun asked Califf if he had reviewed the recommendations the National Academies of Sciences, Engineering, and Medicine made in its 2017 report on the opioid crisis. Califf replied that he was a member of the NASEM and had requested the report during his previous tenure as commissioner in 2016. He noted that the draft guidance addresses one of the most important components of the report, assessing the benefits and risks of a product.
Califf said the agency has a team working on implementing a number of changes in opioid policy, some of which are in process and some of which will come to fruition in the next month. He noted that he gave a speech about the FDA’s plans at the 20 April Rx and Illicit Drug Summit in Atlanta.
One of the agency’s proposals is to require all opioid analgesics used in outpatient settings to be dispensed with prepaid mail-back envelopes. (Also see "US FDA Considering Opioid Mail-Back Envelope Mandate, But Industry Has Heard This Before" - Pink Sheet, 21 Apr, 2022.)
At the summit, Califf noted that the agency is also reexamining the potential utility of blister packaging to stem the problem of accidental ingestion by children and address the problem of clinicians prescribing excessive numbers of tablets in some situations.
In 2019, the FDA sought public comment on the idea of requiring certain solid, oral dosage forms of immediate-release opioid analgesics to be made available in blister packaging for outpatient dispensing. However, industry was largely critical of the proposal with many groups calling for the agency to conduct a study before moving forward. (Also see "Opioid Blister Packs Need Study Before Mandate, Groups Urge " - Pink Sheet, 11 Aug, 2019.)
Among other plans, Califf said the agency is looking for ways to accelerate progress in the development of novel non-addictive treatments for pain, including non-opioid analgesics and medical devices, through better science and facilitation of clinical development.
The FDA is also reconsidering its approach to labeling of opioids to make sure it supports the best prescribing practices. And it is re-examining the role of prescriber education, including the need for a unified, national level education program on managing pain. (Also see "FDA Exploring Partnerships As Alternative To REMS Mandate For Opioid Education" - Pink Sheet, 14 Apr, 2022.)