Understanding the FDA’s Expedited Approval Pathways

Fast Track

The first of these sped-up procedures is coined the Fast Track process. In 2021, 36% of drugs were designated as Fast Track. This process is meant to motivate the development and approval of medication for an unmet treatment area. The FDA states, “the purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions.”

According to the FDA website, while judging whether or not a condition is serious is subjective, an easy way to identify serious conditions is if they will progressively become more severe. Beyond addressing a serious illness, applicants seeking Fast Track designation must produce a product that fills an unmet need, such as providing therapy for a condition where no treatment exists.

Despite the requirement to fill an unmet need, drugs on the Fast Track pathway may treat conditions with available therapy. However, in those cases, a Fast Track approval would require the drug or device to be superiorly effective, reduce or eliminate the side effects of available therapy, improve diagnostic accuracy, decrease toxicity, or address a public health need.

Fast Track designation allows the manufacturer or drug developer to meet and communicate more frequently with the FDA. To receive Fast Track designation, the drug developer must apply for the designation. At this point, the FDA will review and deliver a decision on the designation within 60 days.

“Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients,” stated the organization’s website.

Priority Review

According to the FDA website, the Prescription Drug User Act (PDUFA), established in 1992, set guidelines for drug review times, separating them into standard and priority reviews. A standard review timeline is approximately ten months. However, under a Priority Review designation, the FDA reviews the application over six months.

This type of expedited approval focuses on the evaluation of the drugs. Most commonly, the designation is for medicines that would improve the treatment, diagnosis, or prevention of severe conditions. Other improvements may also include reducing or eliminating drug reactions, enhancing patient compliance, or improving safety and efficacy for a patient subpopulation.

The FDA will categorize each application as a priority or standard review. This occurs without any intervention from the manufacturer or developer; however, applicants may request a priority review.

The FDA states, “It does not affect the length of the clinical trial period. FDA informs the applicant of a Priority Review designation within 60 days of the receipt of the original BLA, NDA, or efficacy supplement. Designation of a drug as ‘Priority’ does not alter the scientific/medical standard for approval or the quality of evidence necessary.”

Breakthrough Therapy

An additional accelerated pathway is the Breakthrough Therapy designation. In 2021, 28% of approved drugs received a Breakthrough Therapy designation. “Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint,” states the FDA website.

Clinically significant endpoints for this kind of designation require measuring the effect of irreversible morbidity or mortality or symptoms. Findings to support a Breakthrough Therapy designation may include an impact on an established surrogate endpoint, intermediate clinical endpoint, other pharmacodynamic biomarkers, or an improved safety profile.

Breakthrough Therapy designation allows applicants the same features as Fast Track designations, guidance on drug development from Phase I trials, and FDA commitment involving senior managers.

The drug company must request a Breakthrough Therapy designation by the end of phase II meetings to utilize the features of the Breakthrough Therapy designation. Despite the request having to come from the manufacturer, the FDA may recommend applying for this designation based on preliminary clinical evidence.

Accelerated Approval

For many medications, the effects and benefits take years to understand or appear. Taking that into account, the FDA has developed procedures to expedite the approval of these medications. The same year the FDA established the PDUFA, it instituted accelerated approval regulations. In 2021, 28% of approved drugs went through the Accelerated Approval pathway.

“These regulations allowed drugs for serious conditions that filled an unmet medical need to be approved based on a surrogate endpoint. Using a surrogate endpoint enabled the FDA to approve these drugs faster,” stated the FDA website.

They define a surrogate endpoint as some measure that can predict or assume clinical benefit. For standard FDA approval, multiple endpoints are required because they cannot be considered measures of clinical benefits alone.

In addition, the FDA website notes, “drug companies are still required to conduct studies to confirm the anticipated clinical benefit. These studies are known as phase IV 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.”

Overall, expedited approval, while more common in recent years, still follows rigorous regulatory procedures.