Compressed Breakthrough Therapy Timelines Require Intensified Upfront Sponsor Dialogue on CMC Plans Internally, With Contractors and With FDA

FDA is stressing that the ability to meet the aggressive expedited review goals of the breakthrough therapy pathway will hinge on the sponsor intensifying its upfront CMC coordination and communication internally, with outside contractors involved with drug substance and product manufacturing, testing and packaging, and with the agency.

As implementation of the breakthrough therapy (BT) provisions of the 2012 FDA Safety and Innovation Act (FDASIA) unfolds (IPQ April 25, 2013), the agency is getting a clearer picture of the CMC challenges involved and what it will take to meet them.

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In a draft guidance on breakthrough and other expedited approval programs released in late-June and in addressing implementation from the podium, FDA is making clear that sponsors will need to develop and present a well thought out CMC plan relatively early in the discussion process, and that a lot more upfront communication and coordination will have to take place among all those involved to assure the plan is viable and executed.

The new 33-page guidance explains how the breakthrough therapy pathway fits in with and combines elements of the other three programs FDA already had in place to facilitate and expedite the development and review of new drugs and biologics that target unmet medical needs for serious conditions: ● fast track ● accelerated approval, and ● priority review.

The agency has also posted on its website and continues to update a Frequently Asked Questions (FAQ) specifically on the BT designation. The FAQ currently addresses about a dozen questions including what the designation means (see box above right), how it differs from the fast track and other expedited review programs, eligibility, and how and when to apply..

While FDA is listing aggregate numbers of BT designation requests received and granted (see box below), the FAQ explains that it cannot disclose information regarding the specific sponsors and therapies, since they are typically submitted at the IND stage when the information is not in the public domain. Companies, on the other hand, have been generally quick to tout the receiving of a BT designation.

As of September 13, press releases had been issued on 22 BT-designated products, which include the name of the drug and the indication sought (an annotated listing of these 22 designations, reflecting the releases, is provided below).

The number of designations as of CDER’s September 6 update was 26.  CBER had not granted a BT designation as of its last August 31 update – having turned down eight of ten, with two decisions pending.

[CLICK HERE for the complete story. Included are insights from an FDA compliance official on the CMC challenges along the BT pathway.  Nonsubscribers can purchase the story for $195 by contacting Karen Bertani ( For subscription/license information, click here.]

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