Access to Unapproved Drugs: FDA Policies on Compassionate Use and Emergency Use Authorization

Summary

The Food and Drug Administration (FDA) regulates the U.S. sale of drugs and biological products, basing approval or licensure on evidence of the safety and effectiveness for a product’s intended uses. Without that approval or licensure, a manufacturer may not distribute the product except for use in the clinical trials that will provide evidence to determine that product’s safety and effectiveness. Under certain circumstances, however, FDA may permit the sponsor to provide an unapproved or unlicensed product to patients outside that standard regulatory framework. Two such mechanisms are expanded access to investigational drugs, commonly referred to as compassionate use, and emergency use authorization.

If excluded from a clinical trial because of its enrollment limitations, a person, acting through a physician, may request access to an investigational new drug outside of the trial. FDA may grant expanded access to a patient with a serious disease or condition for which there is no comparable or satisfactory alternative therapy, if, among other requirements, probable risk to the patient from the drug is less than the probable risk from the disease; there is sufficient evidence of safety and effectiveness to support the drug’s use for this person; and providing access “will not interfere with the ... clinical investigations to support marketing approval.” The widespread use of expanded access is limited by an important factor: whether the manufacturer agrees to provide the drug, which—because it is not FDA-approved—cannot be obtained otherwise. The FDA does not have the authority to compel a manufacturer to participate. Manufacturers consider several factors in deciding whether to provide an investigational drug, such as available supply, perceived liability risk, limited staff and facility resources, and need for data to assess safety and effectiveness. Although FDA reports the number of requests it receives, manufacturers do not.

In the case of determination of a military, domestic, or public health emergency, the Commissioner of Food and Drugs may issue an emergency use authorization (EUA) to allow temporary use of medical products that FDA has not approved or licensed, or unapproved uses for approved or licensed products.

FDA’s assessment of the balance of a drug’s potential risks and benefits—whether for overall market approval or for an individual with a serious disease or a public faced with an unusual and dangerous threat—may vary with the circumstance, such as an individual’s prognosis, threat to the community, alternative available treatments, extent of knowledge of safety and effectiveness in the anticipated use, and informed consent.

Although FDA granted over 99% of the expanded access requests it has received since 2010, patients and others point to what they see as FDA-created obstacles to access. In February 2015, FDA released draft guidance and a new form that, when finalized, would reduce the amount of information required from the physician. Since 2014, 20 states have passed so-called right to try laws to bypass FDA permission for access to an investigational drug.

Congress and FDA seek to protect the public by balancing ensuring that drugs are safe and effective with getting new products to the market quickly. Complementing expanded access programs in achieving those goals are broader tools including incentives to development, expediting development and review, limited access, and regulatory science.