Regulatory Open Forum

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  • 1.  Need guidance

    Posted 25-Feb-2021 13:57
    Hi,

    I have a general question regarding the batches used for registration stability (formal stability). I always remember that the batches used for formal stability need to be manufactured under GMP (in other words, GMP batch); however, in the ICH guidelines, the GMP requirement is not explicitly spelled out. 
    Are there any other regulatory requirements that call out the use of GMP batch(es) for formal stability? What is the rationale for requiring GMP batches for formal stability? Can a batch produced in a non-GMP environment with a protocol-driven process be considered a formal stability batch as long as the process is considered representative to commercial?
    Thank you so much.

    Regards,

    Ming Aquila

    Mobile (908) 720-5336


  • 2.  RE: Need guidance

    This message was posted by a user wishing to remain anonymous
    Posted 25-Feb-2021 17:14
    This message was posted by a user wishing to remain anonymous

    Please be advised, once you said its for registration purposes (i.e. registration NDA/ANDA/BLA...batches), just don't even think of anything else but cGMP!!!! When the FDA has a guidance even for phase 1 batches (i.e. drug product) for human studies to be cGMP, NDA batches must be cGMP standards!. Please read CFR 210 & 211.


  • 3.  RE: Need guidance

    Posted 25-Feb-2021 19:43
    How about the batches used for registration stability only, not for clinical?






  • 4.  RE: Need guidance

    This message was posted by a user wishing to remain anonymous
    Posted 26-Feb-2021 08:56
    This message was posted by a user wishing to remain anonymous

    No non-cGMP batches either for stability only or for marketing can be used for registration purposes. Unless the stability is for research only!


  • 5.  RE: Need guidance

    This message was posted by a user wishing to remain anonymous
    Posted 26-Feb-2021 14:51
    This message was posted by a user wishing to remain anonymous

    Sorry a minor correction: No, non-cGMP batches either for stability only or for marketing can NOT be used for registration purposes. Unless the stability is for research only!


  • 6.  RE: Need guidance

    This message was posted by a user wishing to remain anonymous
    Posted 26-Feb-2021 08:56
    This message was posted by a user wishing to remain anonymous

    Same thing! If I understand your question correctly, you want to use non-cGMP batches for stability to establish your expiry period  and submit the data in the NDA/ANDA etc??? If this is your first NDA, during pre-approval inspection FDA would issue a warning letter!


  • 7.  RE: Need guidance

    Posted 26-Feb-2021 09:53
    Thank you!







  • 8.  RE: Need guidance

    Posted 25-Feb-2021 23:13
    I think I left an important portion out of my email. The non-GMP portion mentioned is for secondary packaging. The primary container closure system is manufactured by a GMP facility. Only the secondary packaging activities were proposed to be done in a protocol-driven process. Thank you.





  • 9.  RE: Need guidance

    Posted 26-Feb-2021 09:13
    Hi Ming.

    I look at this a little simpler.  My question that would need to be answered is whether or not the company would be able/would allow the secondary packaging to be done in a non-GMP manner or by a non-GMP supplier after the IND is approved.  If you wouldn't accept that as part of your production practices in general then I would not generally accept it as part of the official stability lots.  Think about it, mix-ups occurring in the validation and stability batches are just as likely to provide erroneous data as would be reviewed by FDA as a recall.  Everything from using the wrong product secondary package to placing material in the package in the wrong way, etc.  So if you are not going to control your official batches for stability it provides a really strong circumstantial case that you are less than serious about controlling your official commercial production.

    One other strong suggestion for you - whatever you and the company finally decide to do, if you choose to do something outside of the full GMP packaging for your sample batches, make certain that you have an air-tight, bullet-proof explanation of what you did, why you did it, how you did it, what the risk review looks like, etc. before you move forward, keep that document in a secure place where it can be found instantly and be ready to defend it every way possible because you are very likely to need to defend the decision during inspection.

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    Victor Mencarelli
    Global Director Regulatory Affairs
    MelvilleNY
    United States
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