RegulatoryGlossary Term
An FDA program for drugs intended to treat serious conditions where preliminary clinical evidence indicates substantial improvement over available therapies on clinically significant endpoints.
Breakthrough Therapy Designation represents the most intensive FDA expedited program, created by the FDA Safety and Innovation Act of 2012 to accelerate development of drugs that show early evidence of transformative clinical benefit. While Fast Track focuses on drugs that may address unmet need, Breakthrough Therapy requires preliminary clinical evidence of substantial improvement over existing treatments, reflecting a higher bar that identifies drugs with exceptional therapeutic potential deserving the most intensive agency engagement.
The evidentiary standard for Breakthrough Therapy Designation requires preliminary clinical evidence, typically from early-phase trials, demonstrating substantial improvement over available therapy on clinically significant endpoints. The comparison is made to existing treatments, not to placebo, meaning that the drug must show potential to meaningfully advance the therapeutic landscape. The substantial improvement may be based on efficacy, safety, or other clinically meaningful advantages. This evidence requirement distinguishes Breakthrough Therapy from Fast Track, which can be granted based on potential rather than demonstrated benefit.
Drugs with Breakthrough Therapy Designation receive all benefits of Fast Track plus intensive FDA guidance on efficient drug development, organizational commitment involving senior managers, and eligibility for Rolling Review. The intensive guidance includes advice on clinical trial design, use of biomarkers, development strategies that might shorten development time, and FDA involvement in scientific discussions throughout development. This collaborative approach aims to enable efficient development programs that bring transformative therapies to patients as quickly as possible while maintaining appropriate standards for safety and efficacy demonstration.
Oncology development
"The targeted therapy received Breakthrough Therapy Designation after Phase I data showed response rates of 75% in patients with the specific genetic mutation, compared to historical response rates of 20% with standard chemotherapy."
Development efficiency
"Working closely with FDA under Breakthrough Therapy Designation, the sponsor designed a single pivotal trial with an adaptive design that reduced the overall development timeline by two years compared to traditional approaches."
A premarket submission to the FDA demonstrating that a medical device is substantially equivalent to a legally marketed predicate device and therefore does not require premarket approval.
An FDA pathway allowing approval of drugs for serious conditions based on a surrogate endpoint or intermediate clinical endpoint reasonably likely to predict clinical benefit, with post-marketing requirements to confirm the expected benefit.
A regulatory submission to the FDA requesting approval to market a biological product in the United States, demonstrating that the product meets standards for safety, purity, and potency.
An FDA program designed to expedite the development and review of drugs intended to treat serious conditions and fill an unmet medical need, providing increased communication with FDA and eligibility for Rolling Review.
An FDA approval that allows an investigational medical device to be used in a clinical study to collect safety and effectiveness data required to support a premarket approval application or 510(k) submission.
An FDA program for drugs intended to treat serious conditions where preliminary clinical evidence indicates substantial improvement over available therapies on clinically significant endpoints.
Breakthrough Therapy Designation represents the most intensive FDA expedited program, created by the FDA Safety and Innovation Act of 2012 to accelerate development of drugs that show early evidence of transformative clinical benefit. While Fast Track focuses on drugs that may address unmet need, Breakthrough Therapy requires preliminary clinical evidence of substantial improvement over existing treatments, reflecting a higher bar that identifies drugs with exceptional therapeutic potential deserving the most intensive agency engagement.
The evidentiary standard for Breakthrough Therapy Designation requires preliminary clinical evidence, typically from early-phase trials, demonstrating substantial improvement over available therapy on clinically significant endpoints. The comparison is made to existing treatments, not to placebo, meaning that the drug must show potential to meaningfully advance the therapeutic landscape. The substantial improvement may be based on efficacy, safety, or other clinically meaningful advantages. This evidence requirement distinguishes Breakthrough Therapy from Fast Track, which can be granted based on potential rather than demonstrated benefit.
Drugs with Breakthrough Therapy Designation receive all benefits of Fast Track plus intensive FDA guidance on efficient drug development, organizational commitment involving senior managers, and eligibility for Rolling Review. The intensive guidance includes advice on clinical trial design, use of biomarkers, development strategies that might shorten development time, and FDA involvement in scientific discussions throughout development. This collaborative approach aims to enable efficient development programs that bring transformative therapies to patients as quickly as possible while maintaining appropriate standards for safety and efficacy demonstration.
Oncology development
"The targeted therapy received Breakthrough Therapy Designation after Phase I data showed response rates of 75% in patients with the specific genetic mutation, compared to historical response rates of 20% with standard chemotherapy."
Development efficiency
"Working closely with FDA under Breakthrough Therapy Designation, the sponsor designed a single pivotal trial with an adaptive design that reduced the overall development timeline by two years compared to traditional approaches."
A premarket submission to the FDA demonstrating that a medical device is substantially equivalent to a legally marketed predicate device and therefore does not require premarket approval.
An FDA pathway allowing approval of drugs for serious conditions based on a surrogate endpoint or intermediate clinical endpoint reasonably likely to predict clinical benefit, with post-marketing requirements to confirm the expected benefit.
A regulatory submission to the FDA requesting approval to market a biological product in the United States, demonstrating that the product meets standards for safety, purity, and potency.
An FDA program designed to expedite the development and review of drugs intended to treat serious conditions and fill an unmet medical need, providing increased communication with FDA and eligibility for Rolling Review.
An FDA approval that allows an investigational medical device to be used in a clinical study to collect safety and effectiveness data required to support a premarket approval application or 510(k) submission.