Industry is looking for more clarity from FDA on those aspects of the CMC program that can be completed either during application review or post-approval to allow the expedited clearance goals for breakthrough therapies to be realized.
In sorting through the implications of the breakthrough therapy (BT) provisions in the 2012 FDA Safety and Innovation Act (FDASIA), both FDA and industry are recognizing that the compressed clinical timelines provided for push the CMC development process onto the new drug clearance critical path – significantly heightening the profile of the related issues and forcing attention on the constraints of the current CMC review paradigm and how they can be dealt with.
In a draft guidance on breakthrough and other expedited approval programs released in late June and in addressing BT implementation from the podium, FDA has indicated the need for sponsors to develop and present a well thought out CMC plan relatively early in the discussion process – stressing 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 (IPQ April 25, 2013).
Industry, on the other hand, has been wrestling with the problem of how its normal CMC development process will have to be adjusted to keep pace with the expedited clinical timelines and is asking the agency to clarify, in turn, how it is going to provide the regulatory flexibility for these adjustments to be made.
Emerging into high relief in the BT dialogue are the constraints in the current review paradigm and what a regulatory approach would look like that would better accommodate manufacturing and control improvements as more knowledge and experience is gained across the product lifecycle.
Opening the risk/benefit door in the BT context is prompting a reevaluation of the CMC review paradigm in the US that has potentially significant international implications.
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