March 4, 2019Regulatory
The Accelerated Approval Program allows for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval. Drug companies are still required to conduct studies to confirm the anticipated clinical benefit. These studies are known as phase 4 confirmatory trials. If the confirmatory trial shows that the drug actually provides a clinical benefit, then the FDA grants traditional approval for the drug. If the confirmatory trial does not show that the drug provides clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market.
In May 2014, FDA is a Draft Guidance for Industry entitled Expedited Programs for Serious Conditions - Drugs and Biologics. The programs described in this guidance are intended to help ensure that therapies for serious conditions are approved and available to patients as soon as it can be concluded that the therapies' benefits justify their risks. The Agency first formally articulated its thinking on expediting the availability of promising new therapies in regulations codified at part 312, subpart E ( 21 CFR part 312). The subpart E regulations are intended to speed the availability of new therapies to patients with serious conditions, especially when there are no satisfactory alternative therapies, while preserving appropriate standards for safety and effectiveness.
The regulations call for earlier attention to drugs that have promise in treating such conditions, including early consultation with FDA for sponsors of such products and efficient trial design, potentially relying on well-controlled phase 2 studies for evidence of effectiveness. The subpart E regulations specifically recognize that patients and physicians are generally willing to accept greater risks and side effects from treatment of life-threatening and severely debilitating diseases than they would for other diseases. The four principal programs that support these principles are fast track designation, breakthrough therapy designation, accelerated approval, and priority review designation (referred to in this guidance as the Agency's expedited programs). FDA has a history of applying the philosophy underlying subpart E to drugs for rare diseases through use of the Agency's expedited programs. FDA recognizes that certain aspects of drug development that are feasible for common diseases may not be feasible for rare diseases and that development challenges are often greater with increasing rarity of the disease. FDA will continue to apply flexibility in these situations to address particular challenges posed by each disease.