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U.S. Department of Health and Human Services

Regulatory Information

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Frequently Asked Questions: Breakthrough Therapies

1) How many requests for breakthrough therapy (BT) designation have been received by the Food and Drug Administration (FDA) (Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER)) since the Food and Drug Administration Safety and Innovation Act (FDASIA) was signed into law on July 9, 2012?
2) What is breakthrough therapy designation?
Breakthrough therapy designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. A breakthrough therapy designation conveys all of the fast track program features (see below for more details on fast track designation), as well as more intensive FDA guidance on an efficient drug development program. The FDA also has an organizational commitment to involve senior management in such guidance. Section 902 of FDASIA requires the following actions, as appropriate:
  • holding meetings with the sponsor and the review team throughout the development of the drug
  • providing timely advice to, and interactive communication with, the sponsor regarding the development of the drug to ensure that the development program to gather the nonclinical and clinical data necessary for approval is as efficient as practicable
  • taking steps to ensure that the design of the clinical trials is as efficient as practicable, when scientifically appropriate, such as by minimizing the number of patients exposed to a potentially less efficacious treatment
  • assigning a cross-disciplinary project lead for the FDA review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the cross-discipline members of the review team (i.e., clinical, pharmacology-toxicology, chemistry, manufacturing and control (CMC), compliance) for coordinated internal interactions and communications with the sponsor through the review division’s Regulatory Health Project Manager
  • involving senior managers and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review
3) What other programs does FDA have to expedite drug development for serious conditions?
The FDA has various programs that are intended to facilitate and expedite development and review of new drugs to address unmet medical need in the treatment of serious or life-threatening conditions. These expedited programs help ensure that therapies for serious conditions are available as soon as it can be concluded that the therapies’ benefits justify their risks, taking into account the seriousness of the condition and the availability of alternative treatment. These programs include breakthrough therapy designation as noted above, fast track designation, accelerated approval, and priority review. For purposes of this document, all references to “drugs” include both human drugs and biological drug products regulated by CDER and CBER.
Fast Track Designation: Fast Track designation is intended to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Designation may be granted on the basis of preclinical data. A sponsor of a drug that receives fast track designation will typically have more frequent interactions with FDA during drug development. In addition, products that have been designated as fast track can submit portions of a marketing application before submitting the complete application, known as rolling review.
Accelerated Approval:  This program can be used for speeding the development and approval of promising therapies that treat a serious or life-threatening condition and provide meaningful therapeutic benefit over available therapies. Accelerated approval allows approval of a drug that demonstrates an effect on a “surrogate endpoint” that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality (IMM) that is reasonably likely to predict an effect on IMM or other clinical benefit. 
Thus, the accelerated approval pathway is most often useful in settings in which the disease course is long and an extended period of time is required to measure the intended clinical benefit of a drug, even if the effect on the surrogate or intermediate clinical endpoint occurs rapidly. Nevertheless, even after the drug enters the market, the sponsor may be required to conduct post-marketing trials to verify and describe the drug’s clinical benefit. If further trials fail to verify the predicted clinical benefit, the FDA may withdraw approval.
Note that a drug that has received a breakthrough therapy designation or a fast track designation can be eligible for the accelerated approval pathway, if the relevant criteria are met. 
Priority Review: Under the Prescription Drug User Fee Act (PDUFA), FDA agreed to specific performance goals for completing the review and taking an action on an application according to a two-tiered system of review times: Standard Review and Priority Review. Priority review shortens the review goal date to 6 months from the standard review timeline of 10 months.
This review designation is determined at the time of a Biologics License Application (BLA), New Drug Application (NDA), or efficacy supplement submission. Any drug, including those that have received a fast track designation, breakthrough therapy designation, or those being evaluated for accelerated approval, can be granted priority review, if the relevant criteria are met.
4) What are the differences between the breakthrough therapy designation and the fast track designation?
Although breakthrough therapy and fast track designation programs have similarities, as they both are intended to expedite the development and review of drugs for serious or life-threatening conditions, there are differences in what needs to be demonstrated to qualify for the programs. A breakthrough therapy program is for a drug that treats a serious or life-threatening condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint(s) over available therapies. In contrast, a fast track program is for a drug that treats a serious or life-threatening condition, and nonclinical or clinical data demonstrate the potential to address unmet medical need
5) When will “Guidance for Industry” on breakthrough therapies implementation be published?
The draft Guidance for Industry: “Expedited Programs for Serious Conditions––Drugs and Biologics” published on June 25, 2013, and can be found at:
6) Can a request for breakthrough therapy designation be submitted for multiple indications of the same drug?
Yes. A breakthrough therapy designation may apply to a combination of a drug (either alone or in combination with other drugs) and the specific use for which it is being studied. Therefore, a separate breakthrough designation request must be submitted for each proposed development program (i.e., each indication for a drug (or drug combination)).
7) Whom should sponsors contact if they wish to discuss the potential for their product meeting the breakthrough therapy criteria?
The review division managing the Investigational New Drug Application (IND) for the drug in question is the sponsor’s first resource for questions related to the development program of the specific drug, and its potential for breakthrough therapy qualification. If an IND is not yet open, then the contact would be the review division that manages the particular therapeutic area of the proposed indication.
8) Would a clinical trial for a drug that has been designated as a breakthrough therapy generally have to enroll fewer patients prior to approval?
After a development program is designated as a breakthrough therapy, the FDA will work closely with the sponsor to ensure that the design of the clinical trials is as efficient as practicable, when scientifically appropriate. An efficient trial design typically would help minimize the number of patients exposed to a potentially less efficacioustreatment, which could translate to fewer patients enrolled in clinical trials that support marketing approval. Regulatory standards to demonstrate safety and efficacy must still be met.
9) Is a drug that has been granted breakthrough therapy designation still able to submit a request for Special Protocol Assessment (SPA)?
Yes. A breakthrough therapy designation and SPA are two independent regulatory pathways. Therefore, a drug designated as a breakthrough therapy is eligible for SPA, if the protocol meets the criteria for SPA. Conversely, a drug for which an SPA is under review may be considered for breakthrough therapy designation, if the breakthrough therapy designation criteria are met. 
10) Will the FDA announce when a drug has been granted breakthrough therapy designation?
FDA will not disclose information regarding sponsors who submitted requests for or who have been granted or denied breakthrough therapy designation. Breakthrough therapy designation requests are typically submitted to an IND, and the FDA cannot disclose the existence of an IND, or any submissions that have been submitted to the IND, unless it has previously been publicly disclosed or acknowledged per 21 CFR 312.130(a).
11) Does a sponsor have to request breakthrough therapy designation?
Yes, a request to be considered for designation is required. However, the FDA may suggest that the sponsor consider submitting a request for breakthrough therapy designation if: (1) after reviewing submitted data and information (including preliminary clinical evidence), the Agency thinks the drug development program may meet the criteria for breakthrough therapy designation and (2) the remaining drug development program can benefit from the designation.
12) If a product has been designated as a breakthrough therapy, does it need to request fast track designation?
No. All the benefits of fast track designation are available to those who have received a breakthrough therapy designation.
13) If a product is denied breakthrough therapy designation, is it automatically reviewed for fast track designation?
No. Fast track and breakthrough therapy designations are separate programs and require separate requests for Agency consideration.


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