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  • 1.  CMC expectations for Breakthrough Therapy for oncology indication

    This message was posted by a user wishing to remain anonymous
    Posted 30-Nov-2022 09:29
    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?


  • 2.  RE: CMC expectations for Breakthrough Therapy for oncology indication

    This message was posted by a user wishing to remain anonymous
    Posted 30-Nov-2022 11:07
    This message was posted by a user wishing to remain anonymous

    I don't think so in terms of CMC perspective being flexible for API characterization in general and with respect to API cmc requirements given that as you state you had already 6 years in development experience plus you may have more time since the BTD data may still need to be validated! Drug product yes they would be flexible. Just so you are aware there were several instances where BTD products have not reached approval for several reasons.


  • 3.  RE: CMC expectations for Breakthrough Therapy for oncology indication

    Posted 03-Dec-2022 07:49
    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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