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  • 1.  Frozen biologic drug substance

    Posted 16-Jul-2020 15:57
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    Does anyone have experience with Health Authority positions on requirements for annual stability lots for frozen drug substance (biologic)? Are annual stability lots a requirement for frozen DS? Is there room for negotiation? I appreciate your feedback.



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    Annette Hillebrand RAC
    Director Regulatory Affairs CMC
    Novato CA
    United States
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  • 2.  RE: Frozen biologic drug substance

    Posted 17-Jul-2020 08:22
    Dear Annette. According to The ICH guideline, the first three batches should be placed on a long term stability program.f you have produced several batches of the same bulk and have collected Long term stability data and have used the same volumes and container systems you could argue that you do not need to test every year. However, In my experience, companies producing vaccines test for stability periodically while the frozen stock of bulk material is stored. I think that beyond the requirements from the regulatory body it's a good practice to test for potency and purity/impurities at least. Are you thinking of testing just before using the bulk for further processing instead of doing it periodically?

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    Liliana Chocarro
    LC PLUS CONSULTING INC
    Mississauga ON
    Canada
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    Original Message


  • 3.  RE: Frozen biologic drug substance

    Posted 17-Jul-2020 14:57
    Hi Annette,

    Mostly yes. It is a requirement for frozen DS to be put on annual stability (as agreed upon in post-approval stability protocol during BLA). However, there can be exceptions for products with less demand (i.e., products targeting rare diseases).  It can be assumed that you won't need to manufacture DS lots every year to meet the demands. In that case, annual stability can be waived until you manufacture the next lot which will then go on stability as per the approved protocol.

    Once you have gathered enough data (through long term and accelerated conditions) for annual lots and you have better understanding of the stability behavior of your DS and DP, an argument can be made accordingly. FDA is quite amenable to the approach of initiating a dialogue supported by a strong justification. In fact, this topic was covered by an FDA/OBP in one of the conferences I attended this year. Please note that accelerated conditions in annual stability is not unusual and FDA encourages it. 

    All the very best,

    Deep

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    Deep Shah
    Regulatory Affairs CMC, Biologics
    Seattle WA
    United States
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    Original Message


  • 4.  RE: Frozen biologic drug substance

    Posted 20-Jul-2020 15:50
    I second what Deep said. Yes, it is required, but we have always said that if we don't actually manufacture batches in a given year, then none will be put on stability. IOW, we don't manufacture only to have a batch to put on stability annually.

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    Rachel Thornton
    Associate Director
    Smyrna GA
    United States
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    Original Message


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