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FDA Statement

Statement on the FDA’s benefit-risk framework for evaluating opioid analgesics

For Immediate Release:
Statement From:
Norman E. "Ned" Sharpless, MD
Acting Commissioner of Food and Drugs - Food and Drug Administration

Douglas Throckmorton,, M.D.
Deputy Director for Regulatory Programs - Center for Drug Evaluation and Research | CDER

Addressing the crisis of opioid addiction is an issue of great concern for our nation and remains a top public health priority for the FDA. The agency continues to take new steps to confront this crisis, while also paying careful attention to the needs of patients in accessing appropriate pain management. Opioids present unique challenges: they have benefits when used as prescribed yet have very serious risks and can cause enormous harm when misused and abused. We’ve had a robust public debate over the years, engaging the pain and addiction communities, academia, health care professionals and policymakers on developing a framework to help evaluate the benefit-risk considerations specific to prescription opioids that not only serves the patient community but the public health as a whole. Above all, our goal has been 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.

Today, as part of the FDA’s ongoing commitment to assess the benefit-risk of opioid pain medications, the agency issued a new draft guidance, “Opioid Analgesic Drugs: Considerations for Benefit-Risk Assessment Framework,” which describes the application of the benefit-risk assessment framework that the agency uses in evaluating applications for opioid analgesic drugs and summarizes the information that can be supplied by opioid analgesic drug applicants to assist the agency with its benefit-risk assessment, including considerations about the broader public health effects of these products in the context of this crisis. The agency is also withdrawing the 2014 draft guidance, “Analgesic Indications: Developing Drug and Biological Products.” Following discussions with industry and other stakeholders, we believe that the FDA can provide more targeted information in critical areas of development using a series of new draft guidances to speed development.

Benefit-risk assessment is the foundation for the FDA’s regulatory review of human drugs and biologics. These assessments capture the evidence, uncertainties and reasoning used by the agency to arrive at its regulatory decisions. The FDA evaluates a drug product’s risks against its benefits in the context of the use indicated in the labeling. When it comes to regulating opioids, we do so with an understanding that any action taken by the agency should be considered in light of the opioid crisis.

To inform the consideration of how best to assess the benefit-risk of opioid pain medicines, the agency commissioned a study from the National Academies of Science, Engineering, and Medicine to identify additional actions the FDA should consider to address the opioid crisis with 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.

The new draft guidance we’re announcing today 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 under the FDA’s current approval authorities. 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 non-patients, including members of the patient’s household, visiting relatives, friends and others.

Currently, all opioid analgesics intended for outpatient use are subject to one of the FDA-required Risk Evaluation and Mitigation Strategies, or REMS programs. The 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.

Today, the FDA is also announcing that it will hold a public meeting on September 17 to further discuss the agency’s benefit-risk assessment of opioid analgesics, including the manner in which risks of misuse and abuse of these products factor into the benefit-risk assessment. This meeting will include a discussion of whether an applicant for a new opioid analgesic should be required to demonstrate that its product has an advantage over existing drugs in order to be approved and, if so, what new authorities the FDA would need to impose such a requirement. In addition, the agency will discuss whether new preapproval incentives (in addition to existing incentives, such as breakthrough designation) are needed to better support and encourage development of all therapeutics – opioid or non-opioid drugs, biological products or devices – intended to treat pain or addiction.

We also plan to issue additional guidance that will outline appropriate clinical endpoints and clinical trial approaches for the development of non-opioid drugs for use in the treatment of acute and chronic pain.

The FDA’s benefit-risk evaluation does not end once a product is approved; we’re continually reevaluating the safety of approved opioid products based on both post-market data the FDA has required from companies and additional sources of information as part of our safety surveillance. For example, the FDA requested the market withdrawal of reformulated Opana ER based on postmarketing data that demonstrated a significant shift in the route of abuse of Opana ER from nasal to injection following the product’s reformulation, in addition to evidence that injection of the product had been associated with a serious outbreak of HIV and hepatitis C, as well as cases of a serious blood disorder (thrombotic microangiopathy). We’ll continue to apply this same evidence-based decision making as appropriate for other products if there is a shift in the benefits no longer outweighing the risks.

Congress recently enacted new authorities that enable the FDA to, among other things, require post-market studies to evaluate efficacy of opioids and other drugs if we have concerns that these products may not be as effective as previously thought; to require opioids (and other drugs that pose a risk of abuse or overdose) be sold in unit dose packaging; and to require that such drugs be dispensed with packaging or systems that enable the drugs to be safely disposed. This guidance is part of the FDA’s implementation of the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act (SUPPORT Act).

The FDA remains committed to addressing the opioid crisis on all fronts. The agency is focused on decreasing exposure to opioids and helping prevent new addiction by taking novel steps to encourage more appropriate prescribing; supporting the treatment of those with opioid use disorder and promoting the development of improved, as well as lower cost, forms of medication-assisted treatment; fostering the development of novel pain treatment therapies that may not be as addictive as opioids, as well as opioids that are more resistant to abuse and misuse; and taking action against those who contribute to the illegal importation and sale of opioid products. The FDA will also continue to evaluate how drugs currently on the market are used, in both medical and illicit settings, and will take regulatory action where needed.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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