The FDA announced today a new draft guidance for opioid analgesic drugs, and the withdrawal of an earlier draft guidance for these medications.

The new draft guidance “Opioid Analgesic Drugs: Considerations for Benefit-Risk Assessment Framework” describes the application of the benefit-risk assessment framework that the agency uses in evaluating applications for opioid analgesic drugs. It also summarizes the information that can be supplied by opioid analgesic drug applicants to assist the FDA with its benefit-risk assessment, including considerations about the broader public health effects of these products in the context of the ongoing opioid epidemic.

The goal, according to agency officials, is to ensure product approval and removal decisions are science-based and that the agency’s benefit-risk framework considers not only the outcomes of prescription opioids when used as prescribed, but also the public health effects of inappropriate use.

According to a statement issued by the FDA’s Acting Commissioner Norman “Ned” Sharpless, MD and Deputy Director for Regulatory Programs Douglas Throckmorton, benefit-risk assessment is the foundation for the agency’s regulatory review of human drugs and biologics. These assessments capture the evidence, uncertainties, and reasoning used by the agency to arrive at regulatory decisions.

To inform the consideration of how best to assess the benefit-risk of opioid pain medicines, the FDA commissioned a study from the National Academies of Science, Engineering, and Medicine to identify additional actions that should be considered to address the opioid epidemic. There was a particular focus on approaches the agency can take to improve its benefit-risk framework for opioids to support a more formal assessment of the public health risks associated with opioids. The FDA developed the new draft guidance with this study’s recommendations in mind, according to agency officials.

The new draft guidance describes what information the FDA recommends companies provide in their opioid analgesic new drug applications in order for the agency to fully assess the benefits and risks, and the public health implications of approving their product. The agency will consider the benefits and risks of proposed new opioid analgesics relative to other already approved opioid and non-opioid analgesics.

In terms of patient safety, the agency recommends that companies consider providing information on whether their drug has any characteristics that would mitigate the risks of overdose, abuse or the development of addiction. Companies should also indicate whether their drugs have novel or greater risks compared to other opioids on the market and also note the public health implications of their products in terms of risks to nonpatients, such as household members.

Currently, all opioid analgesics intended for outpatient use are subject to 1 of the FDA-required Risk Evaluation and Mitigation Strategies (REMS) programs. The new draft guidance recommends that companies consider whether new products present a different safety profile than those products covered by a currently approved REMS. If so, the company should propose a REMS to ensure that the benefits of the drug outweigh the risks.

In addition to releasing a new draft guidance, the FDA is also withdrawing the 2014 draft guidance, “Analgesic Indications: Developing Drug and Biological Products.” Based on discussions with industry and other stakeholders, Sharpless and Throckmorton said, they believe the FDA can provide more targeted information in critical areas of development using a series of new draft guidances that will speed development.

The FDA will hold a public meeting September 17 to discuss further the agency’s benefit-risk assessment of opioid analgesics. An additional guidance outlining appropriate clinical endpoints and clinical trial approaches for the development of non-opioid drugs for use in the treatment of acute and chronic pain also is planned.


Statement on the FDA’s benefit-risk framework for evaluating opioid analgesics [news release]. Silver Spring, MD; June 20, 2019: FDA website. Accessed June 20, 2019.