Breakthrough Therapy Designation

Breakthrough Therapy Designation (BTD) is a rather new drug designation category that was signed into law with the approval of the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012. Drugs which are designated as a breakthrough therapy showcase significant improvement upon current therapies and its planned outcome. 


FDASIA Section 902 specifically relates to the BTD, which was put in place as a means to accelerate the “development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).” A drug which receives BTD is eligible for similar benefits as the Fast Track designation (FTD), with additional guidance from FDA on the drug’s development program as early as phase 1 and organizational commitment involving senior managers.


The approval of a BTD depends on evidence demonstrating the proposed drug or therapy shows improvement in efficacy, safety, or a major contribution to patient care over the currently available therapy options. In reference to the exact language and terminology surrounding the meaning of the “improvement over available therapy on a clinically significant endpoint(s),” often translates to if the therapy delivers better results on irreversible morbidity or mortality (IMM) and other factors that show serious consequences of the disease.   


However, other observed clinical endpoints that may showcase medical superiority can include: 

  • An effect on an established surrogate endpoint
  • An effect on a surrogate endpoint or intermediate clinical endpoint considered reasonably likely to predict a clinical benefit (i.e., the accelerated approval standard)
  • An effect on a pharmacodynamic biomarker(s) that does not meet criteria for an acceptable surrogate endpoint, but strongly suggests the potential for a clinically meaningful effect on the underlying disease
  • A significantly improved safety profile compared to available therapy (e.g., less dose-limiting toxicity for an oncology agent), with evidence of similar efficacy

The BTD is just one of several drug designation programs that the FDA offers in an effort to expedite certain therapies to market. Other designation programs include FTD, Priority Review, Accelerated Approval, and more.

Breakthrough Therapy Designation vs. Fast Track Designation


BTD and FTD are two entirely different drug approval programs, but their definitions can make it seem like overlap exists. It is important for a sponsor or pharmaceutical developer to understand the key differences between the two programs to understand which designation applies to their therapy solution. 

The differentiators by definition center around the area of application. Both programs are intended to fast-forward the development and approval process for new therapies to treat serious or life-threatening conditions. BTD is intended for drugs which show a significant benefit over currently existing treatments, while FTD therapies are intended to treat unmet medical needs relating to the serious condition.


Fast Track

Breakthrough Therapy

Program Goal

Drug Designation

Drug Designation

Approval Criteria 

  • A therapy intended to treat a serious condition and nonclinical or clinical data shows the potential to address an unmet medical need 
  • A drug that has been designated as a qualified infectious disease product
  • A drug that is intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinical endpoint over currently available therapies 

When to Submit a Request

  • With the IND or after 
  • As soon as sufficient data is available to show the drug’s potential to address an unmet medical need 
  • With the IND or after 
  • No later than the EOP2 meeting

FDA Response Timeline

  • Within 60 days of receiving the request
  • Within 60 days of receiving the request 

Designation Features 

  • Actions to expedite drug development and review 
  • Rolling review 
  • All Fast Track features 
  • Intensive guidance on an efficient drug development program, beginning as early as Phase 1
  • Organizational commitment involving senior managers

Breakthrough Therapy Designation Timeline & Approval Process


A BTD is traditionally requested by the drug sponsor. It may be made concurrently with, or at any time after, the submission of an Investigational New Drug (IND) application. A request should be sent to the FDA no later than the end of Phase 2 meetings. The FDA may suggest a sponsor submit a request for approval if: 


  1. Post reviewing the submitted data and information (including preliminary clinical evidence), the FDA believes the drug development program may meet the qualifying criteria for Breakthrough Therapy designation 
  2. The remaining drug development program can benefit from the designation 


The FDA will respond to application submission requests within 60 days. 


If a sponsor is in need of help with their BTD application, the FDA does offer optional guidance prior to the formal submission. A sponsor can contact the regulatory project manager (RPM) in the division where their active IND is assigned and ask for the “Preliminary Breakthrough Therapy Designation Request Advice” template. This template should then be sent as a formal amendment to the IND and a virtual meeting teleconference between the sponsor and the review division will be organized. 


For the fiscal year of 2021, the FDA received 113 BTD applications with:  


  • 45 requests being granted 
  • 44 being denied 
  • 12 being withdrawn 
  • The remaining pending a decision

Breakthrough Therapy Designation Guidance


Understanding the components of the BTD program can be complex. Even with the help of an FDA regulatory project manager and the guidance documents put together by the administration, questions, missteps, and errors occur on the part of the petitioning sponsors. 


At Biopharma Global, we are regulatory affairs experts who specialize in a variety of drug designation programs like the BTD. We are able to provide in-depth, direct guidance to sponsors on how to meet and exceed application requirements and supporting information. In our years of experience dealing with the FDA approval process and stringent protocol guidelines, we have been able to successfully help several pharmaceuticals receive approval and get to market for patient use. Our staff has submitted countless applications for a variety of indications and has a 100% success rate when clients follow our instructions. 


If you are in the process of applying for Breakthrough Therapy Designation, contact us today to learn how we can help you submit a successful application. 

Biopharma Global - FDA & EMA Regulatory Affairs Consulting Services