Fast Track, Accelerated Approval and Priority Review

Accelerating Availability of New Drugs for Patients with Serious Diseases

Speeding the development and availability of drugs that treat serious diseases are in everyone's interest, especially when the drugs are the first available treatment or have advantages over existing treatments.  The Food and Drug Administration (FDA) has developed three distinct and successful approaches to making such drugs available as rapidly as possible: Priority Review, Accelerated Approval, and Fast Track.  Because each of these approaches implies speed, there can be confusion about the specific meaning of each and the distinctions among them.

The following summary describes each element, how they differ, and how they complement each other.

Fast Track
Accelerated Approval
Priority Review
Comparison of Approval Times for Priority and Standard Review Drugs between 1993 and 2003

Fast Track

Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and fill an unmet medical need.  The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases. 

Determining whether a disease is serious is a matter of judgment, but generally is based on whether the drug will have an impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one.  AIDS, Alzheimer’s, heart failure and cancer are obvious examples of serious diseases.   However, diseases such as epilepsy, depression and diabetes are also considered to be serious diseases.

Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially superior to existing therapy.

Any drug being developed to treat or prevent a disease with no current therapy obviously is directed at an unmet need.  If there are existing therapies, a fast track drug must show some advantage over available treatment, such as:

• Showing superior effectiveness
• Avoiding serious side effects of an available treatment
• Improving the diagnosis of a serious disease where early diagnosis results in an improved outcome
• Decreasing a clinically significant toxicity of an accepted treatment

A drug that receives Fast Track designation is eligible for some or all of the following:

• More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval
• More frequent written correspondence from FDA about such things as the design of the proposed clinical trials
• Eligibility for Accelerated Approval, i.e., approval on an effect on a surrogate, or substitute endpoint reasonably likely to predict clinical benefit
• Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the application is completed before the entire application can be reviewed.  NDA review usually does not begin until the drug company has submitted the entire application to the FDA, and
• Dispute resolution if the drug company is not satisfied with an FDA decision not to grant Fast Track status. 

In addition, most drugs that are eligible for Fast Track designation are likely to be considered appropriate to receive a Priority Review. Fast Track designation must be requested by the drug company.  The request can be initiated at any time during the drug development process.  FDA will review the request and make a decision within
sixty days based on whether the drug fills an unmet medical need in a serious disease.

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.

Accelerated Approval

When studying a new drug, it can take a long time - sometimes many years - to learn whether a drug actually provides real improvement for patients – such as living longer or feeling better.  This real improvement is known as a “clinical outcome.”  Mindful of the fact that obtaining data on clinical outcomes can take a long time, in 1992 FDA instituted the Accelerated Approval regulation, allowing earlier approval of drugs to treat serious diseases, and that fill an unmet medical need based on a surrogate endpoint. 

A surrogate endpoint is a marker - a laboratory measurement, or physical sign - that is used in clinical trials as an indirect or substitute measurement that represents a clinically meaningful outcome, such as survival or symptom improvement. The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval.

Approval of a drug based on such endpoints is given on the condition that post marketing clinical trials verify the anticipated clinical benefit.

The FDA bases its decision on whether to accept the proposed surrogate endpoint on the scientific support for that endpoint.  The studies that demonstrate the effect of the drug on the surrogate endpoint must be “adequate and well controlled” studies, the only basis under law, for a finding that a drug is effective.

Use of a surrogate can save valuable time in the drug approval process.  For example, instead of having to wait to learn if a drug actually can extend the survival of cancer patients, the FDA might now approve a drug based on evidence that the drug shrinks tumors because tumor shrinkage is considered reasonably likely to predict a real clinical benefit.  In this example, an approval based upon tumor shrinkage can occur far sooner than waiting to learn whether patients actually lived longer.  The drug company will still need to conduct studies to confirm that tumor shrinkage actually does predict that patients will live longer. 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 for patients, FDA has regulatory procedures in place that could lead to removing the drug from the market.

Priority Review

Prior to approval, each drug marketed in the United States must go through a detailed FDA review process.  In 1992, under the Prescription Drug User Act (PDUFA), FDA agreed to specific goals for improving the drug review time and created a two-tiered system of review times – Standard Review and Priority Review.

Standard Review is applied to a drug that offers at most, only minor improvement over existing marketed therapies.  The 2002 amendments to PDUFA set a goal that a Standard Review of a new drug application be accomplished within a ten-month time frame.

A Priority Review designation is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists.  A Priority Review means that the time it takes FDA to review a new drug application is reduced.  The goal for completing a Priority Review is six months.

Priority Review status can apply both to drugs that are used to treat serious diseases and to drugs for less serious illnesses. The FDA goal for reviewing a drug with Priority Review status is six months.

The distinction between priority and standard review times is that additional FDA attention and resources will be directed to drugs that have the potential to provide significant advances in treatment.
Such advances can be demonstrated by, for example:

• evidence of increased effectiveness in treatment, prevention, or diagnosis of disease;
• elimination or substantial reduction of a treatment-limiting drug reaction;
• documented enhancement of patient willingness or ability to take the drug according to the required schedule and dose; or
• evidence of safety and effectiveness in a new subpopulation, such as children.

A request for Priority Review must be made by the drug company. It does not affect the length of the clinical trial period.  FDA determines within 45 days of the drug company’s request whether a Priority or Standard Review designation will be assigned.  Designation of a drug as “Priority” does not alter the scientific/medical standard for approval or the quality of evidence necessary.

SUMMARY

Fast Track, Accelerated Approval and Priority Review are approaches that are intended to make therapeutically important drugs available at an earlier time.  They do not compromise the standards for the safety and effectiveness of the drugs that become available through this process. 

These revitalized FDA drug review approaches have yielded tangible results in bringing safe and effective drugs to patients with serious diseases more quickly. For example, since 1996, 68 drugs for cancer therapies have received priority review and approval. 

FDA reviewed Gleevec, a treatment for chronic myeloid leukemia, in four months.  Shortened review times have also brought promising treatments to patients with HIV/AIDS more quickly.  Kaletra for the treatment of HIV/AIDS was reviewed and approved in 3.5 months. Pegasys, a combination product for the treatment of Hepatitis C was approved for marketing in 4 months.

The table below illustrates the improvement in FDA review times in the years between 1993 to 2003.  The median time required to review a priority review drug was reduced from 13.9 months to 6.7 months.

Fast Track, Accelerated Approval, and Priority Review have evolved over time. FDA has been vigilant in assuring that reducing the time necessary for drug development has not compromised the safety and effectiveness of drugs for patients with serious diseases.

Comparison of Approval Times for Priority and Standard Review Drugs

Calendar Years 1993-2003