Frequently Asked Questions: Breakthrough Therapies
CDER and CBER Breakthrough Therapy Requests Received
CDER and CBER Breakthrough Therapy Approvals
- CDER Approvals for Breakthrough Therapy Designated Drugs
- CBER Approvals for Breakthrough Therapy Designated Drugs
CDER and CBER Breakthrough Therapy Withdrawn After Granting (WAG) and Rescinded
- CDER Breakthrough Therapy Designation Withdrawn After Granting (WAG) and Rescinded
- CBER Breakthrough Therapy Designation Withdrawn After Granting (WAG) and Rescinded
- 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, 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
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 obtain 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 that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit.
Priority Review: As part of its commitments in PDUFA V, FDA has established a review model, the Program. The Program applies to all new molecular entity NDAs and original BLAs, including applications that are resubmitted following a Refuse-to-File action, received from October 1, 2012, through September 30, 2017. For applications filed by FDA under the Program, the PDUFA review clock will begin at the conclusion of the 60 calendar day filing review period that begins on the date of FDA receipt of the original submission.
MAPP 6025.6 “Good Review Practice: Management of Breakthrough Therapy-Designated Drugs and Biologics” was published on July 29, 2014.
- PRIME and the US breakthrough therapy designation share the same objective (timely patient access to innovative medicines) but have a different legal basis, hence comparison and harmonization is difficult.
- In late 2016, as part of the confidentiality arrangements, FDA and EMA began regular exchange of information and meetings regarding breakthrough therapy designation and PRIME eligibility requests, focusing on high level topics and comparing general experience and program implementation challenges.
- In this context, FDA and EMA track submitted requests for PRIME and breakthrough therapy designations and compare final review outcomes, including specific reasons for a designation request denial.
- These meetings facilitate increased awareness of FDA/EMA dually designated products and stimulate early dialogue by therapeutic area experts in both regions on an ad hoc basis within the existing clusters, or in the context of Parallel Scientific Advice (PSA) program via a formal meeting.
- The agencies do not routinely share scientific and regulatory reviews regarding dually designated product development programs or marketing applications, unless a topic of specific interest has been defined by the agencies’ subject matter expert teams or sponsors.
- When requesting breakthrough therapy designation or eligibility to PRIME, sponsors are encouraged to inform the agency whether they have submitted a request for designation or eligibility to the other agency and the outcome of this request.
- For successful planning of global development and clinical studies, both agencies encourage sponsors to contact FDA and EMA on a dually designated product’s development program and seek joint advice under the PSA program. Sponsors wishing to nominate a product for a PSA procedure should address one single “Request for PSA” letter to both email@example.com at EMA and OC-OIP-Europe@fda.hhs.gov at FDA.