Breakthrough Designation Speeds Up Approval but Strains FDA’s Resources
[Posted on: Thursday, 24 March, 2016]

The breakthrough therapy designation (BTD) has been lauded as one of the most innovative of regulatory pathways as it modifies the conventional drug development, review and approval processes to speed up availability of new drugs to the patients. Since its implementation in 2012, more than 100 drugs have obtained this designation and already 39 new drugs have been approved under this pathway, mostly for treatment of cancer. In a survey published earlier this month, it was found that drug designated as breakthrough by FDA get to market in about 5.2 years compared to 7.4 years for the non-breakthrough drugs. It is obvious that the authors included time to development prior to introduction of this pathway. Also, it would be hard to compare drugs developed prior to 2012 with the drugs developed currently since other factors may have played a role in the overall development time-line for a given product. These include orphan designation, accelerated approval product, fast-track designation, first treatment for an untreatable indication, and novel mechanism of action, most of which applies to drugs currently designated as breakthrough. That said, the advantages of breakthrough designation to bring products to patients is unquestionable. While FDA has been very supportive of the breakthrough designations and has diligently reviewed and approved drugs designated as such, expectedly FDA resources are stretched thin to meet the demand of quicker turnaround. A sponsor’s breakthrough therapy designation request (BTDR) goes through an extensive multi-level review at the FDA. In an effort to make the BTDR review process more efficient, FDA has always advised that prior to submitting a BTDR, the sponsor contact the project managers in the division where the request will be submitted to seek preliminary advice regarding appropriateness of the BTD at the time of request. Hereby the sponsor could get feedback from the review division regarding sufficiency of supporting data and the targeted indication before submitting a formal BTDR. The FDA division could grant a short 15 min teleconference to discuss with the sponsor. Although FDA will not give any written minutes or go into much details, it could be a good way for both the sponsor and FDA to avoid going through the detailed BTDR review. With the rejection rate of BTDR being more than 60% this seems like a good idea. Recently, a respected blog published the details of this preliminary BTDR process, along with the preliminary advice template. Getting a negative feedback does not necessarily preclude a sponsor from still submitting the BTDR. While this may seem like a good idea, few sponsors use the preliminary process. The main reason being that even if one gets a negative decision to their BTDR, the detailed rationale provided by FDA to reject an application could be valuable for further development of the product and re-filing the BTDR at a later time. The preliminary process could be used by sponsors who are not seriously planning a BTDR but want to get some early feedback from FDA. So, this may further strain the resources at FDA with sponsor bringing clearly half-baked ideas to get free feedback. There is no public data on how many preliminary BTDR meetings FDA grants and the outcome. But the pros and cons of the process are obvious.