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November 1, 2021 Regulatory Affairs

FDA’s Expedited Programs Explained

Erica Berzin, MS Regulatory Affairs Director and Consultant

In order to incentivize the development of therapies (drugs biologics) to fill unmet medical needs for treatment of serious conditions, FDA has developed various programs to expedite drug development and review. These four programs are: fast track, breakthrough therapy, accelerated approval, and priority review. Over the years, we have learned that guiding clients through the process and selecting the right procedure can have great benefit. Understanding which track best suits each product substantially aids in creating an effective regulatory strategy and drug development program.

Before discussing the programs in detail, it is useful to review some definitions:

Serious condition:

  • Is a “disease or condition associated with morbidity that has substantial impact on day-to-day functioning. Short-lived and self-limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible if it is persistent or recurrent.”
  • “all conditions meeting the definition of life-threatening…would also be serious conditions”

Available therapy:

  • “is approved or licensed in the United States for the same indication being considered for the new drug”
  • “is relevant to the current U.S. standard of care (SOC) for the indication”

Unmet medical need:

  • “is a condition whose treatment or diagnosis is not addressed adequately by available therapy.”
  • Examples include:
    • Where there is no available therapy
    • Where there is available therapy:
      • Drug has effect on a serious outcome that is not known to be influenced by available therapy
      • Drug shows improved effect on a serious outcome compared with available therapy
      • Drug has effect on serious outcome in patients who are unable to tolerate or fail to respond to available therapy
      • Drug can be used effectively with other agents that cannot be combined with other therapy
      • Drug provides comparable efficacy to available therapy while avoiding serious side effects
      • Drug has comparable safety and efficacy to available therapy but has a documented benefit
      • Drug addresses an emerging or anticipated public heath need
    • Where the only available therapy was approved under accelerated approval and clinical benefit has not been verified post-approval

There is often confusion regarding these four programs, as they have many similarities and overlapping benefits. All four programs are designed to address an unmet medical need for a serious condition.

Here, we summarize the procedural guidance from FDA regarding these programs, with an emphasis on comparing and contrasting the four programs. The table below and following information provides an overview of all four of FDA’s expedited programs.

Type of Data Required Data Should Demonstrate Benefits
Fast Track Designation Preliminary nonclinical, mechanistic, or clinical data Potential to address an unmet medical need for a serious condition
  • More frequent meetings with FDA
  • More frequent written communication from FDA
  • Rolling review
Breakthrough Therapy Designation Preliminary clinical data Substantial improvement on clinically significant endpoint(s) over available therapies
  • More frequent meetings with FDA
  • More frequent written communication from FDA
  • Rolling review
  • Intensive guidance on an efficient drug development program
  • Involvement of FDA senior managers to expedite development
Accelerated Approval Pathway Not specified; Sponsor should make justification of alternate endpoint based scientific support Generally provides a meaningful advantage over available therapies AND demonstrates an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit or a clinical endpoint that can be measured earlier than irreversible morbidity or mortality
  • Approval based on a surrogate or intermediate endpoint (often allows for shorter development time) Note: FDA requires clinical trials to be conducted post-approval to confirm clinical benefit
Priority Review Designation Data contained in the final NDA submission Significant improvement in safety or effectiveness of the treatment, prevention, or diagnosis of a serious condition
  • Review of application in 6 months

Fast Track Designation

The Fast Track Designation  helps to facilitate the development and expedite the review of new drugs that treat a serious medical condition and fill an unmet medical need. By speeding up these processes, new drugs can get to patients in need faster than they normally would through standard tracks.

Breakthrough Therapy Designation

Breakthrough Therapy Designation from the FDA helps expedite the development and review of new drugs that may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. The determination of whether the improvement over available therapy is substantial and depends on the magnitude of treatment effect including the effect duration and observed clinical outcome.

Fast Track vs. Breakthrough Therapy

Fast Track and Breakthrough Therapy are the most similar programs designed to expedite the development of drugs for serious conditions. The most significant difference in these two programs is related to the type of data needed to substantiate the request. Fast Track Designation can be granted based on preliminary data, such as activity in a nonclinical model or pharmacological data, or a mechanistic rationale. Breakthrough Therapy Designation must use preliminary clinical data, and therefore activity in a nonclinical model or a mechanistic rationale alone would not be sufficient.

Sponsors should also note the subtle differences in the designation criteria: drugs seeking Fast Track Designation must only have the potential to address an unmet medical need, while drugs seeking Breakthrough Therapy Designation must have preliminary data which demonstrate substantial improvement on clinically significant endpoints over available therapies. The benefits of Fast Track Designation are more frequent meetings with FDA, more frequent written communication from the Agency, and rolling review. Rolling review refers to the ability of FDA to begin review of the NDA as sections are completed, rather than waiting for complete submission the entire NDA to begin review. Breakthrough Therapy Designation drugs receive all the benefits of Fast Track drugs, but also are given intensive guidance on an efficient drug development program and have the involvement of FDA senior managers. It is not uncommon for a drug with Fast Track Designation to be granted Breakthrough Therapy Designation during the drug development process.

Accelerated Approval

Accelerated Approval is the most unique of the programs for drugs intended to treat a serious disease because it is an approval pathway rather than a designation. An approval pathway is a mechanism to market authorization whereas a designation is granted to a drug based on meeting certain criteria. A designation provides certain benefits, such as expediting the approval process (for priority review designations) or providing tax credits and exclusivity (for orphan drug designations).

Accelerated approval allows for the use of a surrogate endpoint that is reasonably likely to predict clinical benefit or an intermediate clinical endpoint that can be measured earlier than irreversible morbidity or mortality. Drugs using the accelerated approval pathway must also generally provide a meaningful advantage over available therapies.

Accelerated approval has an important commitment; the Sponsor is required to conduct additional clinical trials after the drug is approved to confirm the clinical benefit. Until the benefit has been confirmed in a post-market setting, the labeling has special language to indicate that the use of the drug has not yet been shown to have a clinical benefit. Additionally, if a drug fails to show a clinical benefit after approval, the drug can be removed from the market.

Priority Review

The final expedited program is Priority Review, which is requested by a Sponsor at the time of NDA submission. While most NDAs have a 10-month goal date, priority review drugs have a 6 month goal date. In order to qualify for priority review, the Sponsor must show that if approved, the drug would provide a significant improvement in safety or effectiveness of the treatment, prevention, or diagnosis of a serious condition.

Contact ProPharma Group for Expert Guidance on Expedited Programs

If you think your drug may be eligible for one or any of the expedited programs, have additional questions about one or all of the programs, contact ProPharma Group. ProPharma Group is the global leader in regulatory science consulting services with over 35 years of experience helping companies of every size across the world achieve success with the FDA.

We’ll use our extensive knowledge and experience working directly with the FDA to facilitate a successful interaction with the Agency. Contact us to learn more about our services and get started today.

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