Although it may not contain the precise answer to your question, I would recommend you review the
recently posted MAPP from FDA regarding Quality Assessments for Products in Expedited Programs, which incidentally becomes effective next week. It provides a good level of detail about how FDA considers regulatory flexibility in such situations.
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Jonathan Amaya-Hodges
Director, Technical Services
Sharon MA
United States
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Original Message:
Sent: 30-Nov-2022 01:36
From: Anonymous Member
Subject: CMC expectations for Breakthrough Therapy for oncology indication
This message was posted by a user wishing to remain anonymous
FDA has granted Breakthrough Therapy designation for a small molecule drug candidate for an oncology indication. I would be grateful for any comments on the likelihood that FDA would accept an NDA under the following circumstances:
- Only one registration stability batch of API and drug product has been made
- No stability data are available yet for the registration stability batch, but the clinical batches made by a slightly different process were stable for more than 6 years at 25/60 and 6 months at 40/75
- Due to substantial challenges in purification, structural characterization and synthesis, some impurities that exceed the ID threshold are identified only tentatively and have not been isolated in pure form as reference standards. However, the specifications for these impurities can be justified based on their levels in the tox batch.
- In relation to a different IND for a non-life-threatening indication, FDA indicated that one of the proposed regulatory starting materials (RSMs) did not meet their expectations for an RSM. Might they be more flexible, given Breakthrough Therapy status for a life-threatening indication?