FDA Accelerated Approval Program

What Is the FDA Accelerated Approval Program?

The Accelerated Approval Program allows drugs for serious conditions that fill an unmet medical need to be approved based on an expected benefit rather than benefits demonstrated through years of clinical trials and studies. This program was instituted in 1992 in order to speed up the approval process for life-saving medications used to treat serious, life-threatening conditions.   

Why Is the FDA’s Accelerated Approval Program Necessary?

The Accelerated Approval Program’s goal is to approve drugs and medical devices to treat serious and fatal illnesses. This is necessary to get the drugs and medical devices on the market as quickly as possible to help those patients in need. 

What Tests Does the FDA Require in the Accelerated Approval Program?

Even after accelerated approval, drug companies are still required to conduct studies and clinical trials to confirm the anticipated clinical benefit. If the trials show the drug does provide the clinical benefit, then the FDA grants traditional approval. On the other end, if the trial doesn’t show that the drug provides a clinical benefit, the FDA has procedures that could remove the drug from the market. 

How Is the Accelerated Approval Program Different From the FDA’s Traditional Approvals Process?

The accelerated approval allows earlier access to treatments that can help save and extend patient’s lives. One of the main differences is the way in which the drug or medical device is tested. Through traditional approvals, the process can take a long time to determine whether the drug actually produces results and can be beneficial for patients. The Accelerated Approval Program doesn’t require the actual proof of results before approval, but instead only requires a predicted outcome through a measured point. 

How Does a Drug Get Approved Through the Accelerated Approval Program?

The FDA bases its decision to accept the surrogate or intermediate clinical endpoint on the scientific support for that endpoint. Instead of having to wait to learn if a drug actually extends survival for cancer patients – since that would take years or decades to confirm – the FDA can approve a drug based on the evidence currently available. The drug company will still need to conduct ongoing studies. Approval of a drug may be withdrawn or the label can be changed if the trials fail to verify the clinical benefit or do not demonstrate sufficient clinical benefits to justify the risks associated with the drug.

What Is a Surrogate Endpoint?

A surrogate endpoint used for accelerated approval is a marker – a lab measurement, radiographic image, physical sign, or another measure that predicts clinical benefit, but is not the clinical benefit itself. 

What Is an Intermediate Clinical Endpoint?

Similarly to a surrogate endpoint, an intermediate clinical endpoint is a measure of a therapeutic effect that is considered likely to predict the clinical benefit of a drug, like preventing irreversible morbidity and mortality (IMM).

What Is the Controversy Surrounding the Accelerated Approval Program? 

The FDA Accelerated Approval Program has garnered a great deal of controversy since it was adopted. The program is often criticized for rushing certain drugs and devices to the market without sufficient proof of their efficacy. It is estimated that 10 percent of accelerated approvals in the oncology market fail in post-marketing studies. This translates to ineffective drugs and devices being used by patients who are in critical need of effective treatment. Additionally, approval through the FDA Accelerated Approval Program may fail to identify deadly side effects that result from the use of the product.

How Do Delays in Post-Marketing Studies Affect Patients? 

After a product is approved under the FDA Accelerated Approval Program, manufacturers are still required to conduct post-marketing, confirmatory studies. If the confirmatory trial shows clinical benefit, the product receives traditional FDA approval. If it does not, FDA regulatory procedures may be used to remove the drug from the market. However, several manufacturers fail to provide timely post-marketing study results.

When Was the Accelerated Approval Program at Fault?

In 2000, Pfizer received accelerated approval for a treatment for acute myeloid leukemia (AML). Unfortunately, the study was not conducted until four years after the drug was approved under the FDA Accelerated Approval Program. Pfizer withdrew the drug in 2010. The withdrawal took place because clinical studies showed a lack of clinical benefit from the drug. Additionally, an unexpected number of deaths occurred in patients using the drug.

What Changes Are Being Implemented by the FDA to the Accelerated Approvals Program?

In 2011, the FDA discussed changes to the FDA Accelerated Approval Program. Several FDA officials suggested using an existing provision within a 2007 law. This provision would result in a fine of up to $10 million for companies that failed to conduct timely post-marketing studies. Additionally, the FDA discussed that post-marketing studies began before accelerated approval was granted to a product. This way, manufacturers would be unable to postpone clinical studies.

What Are the Food and Drug Amendments of 2022?

The Food and Drug Amendments of 2022 grant the FDA explicit legal authority to require confirmatory studies prior to accelerated approval, setting of targets, and biannual reporting of study progress. The legislation also includes an expedited withdrawal procedure that can happen if the sponsor fails to conduct the required postapproval study, the confirmatory study does not confirm benefit, other evidence shows the product is not safe and effective, or the sponsor produces misleading promotional materials.