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  • 1.  Aseptic and terminal sterilization

    This message was posted by a user wishing to remain anonymous
    Posted 18-Feb-2021 13:59
    This message was posted by a user wishing to remain anonymous

    Is it possible to include both aseptic and terminal sterilization for a parenteral product in the NDA dossier


  • 2.  RE: Aseptic and terminal sterilization

    Posted 18-Feb-2021 16:55
    It is possible to do this but my question is why would you?  If you believe that the product "needs" aseptic filling and that your facility is capable of managing aseptic filling operations then terminal sterilization is a waste of time and money.  If you are afraid your product might become contaminated and you are going to head off any issues with terminal sterilization then you are effectively saying you not confident in your process. If your product is something that might need o be sterilized post-processing for other reasons (e.g. your product is biotechnologically derived and you need to remove any organisms/cells that might have been able to get through the filtration or other aseptic filling process) then I might start asking myself or my facility engineers and microbiologists whether it makes sense just to send it through terminal sterilization rather than pushing through both options.  Just remember - terminal sterilization will kill organisms or cells but if you are worried about pyrogens, then killing the organisms might actually increase the potential for pyrogenicity so you need to be very careful about your plans, and very clear on what you are trying to manage/avoid/prevent.

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    Victor Mencarelli
    Global Director Regulatory Affairs
    MelvilleNY
    United States
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    Original Message


  • 3.  RE: Aseptic and terminal sterilization

    Posted 19-Feb-2021 17:40
    Dear Anonymous,

    I am not totally clear about your question. Please elaborate considering the following scenarios.

    1. Normally sterile parenteral products need to be filled aseptically to ensure the environment is clean and free of contamination. Additionally, the filling equipment needs to be terminally sterilized before used for aseptic filling processes. So you need to provide validation data for both aseptic filling and terminal sterilization of the equipment in NDA.
    2. In cases where the drug itself can withstand a terminal sterilization process (such as high temperature autoclaving), it can be terminally sterilized. Like Victor pointed out, you don't need to do both and just pick one of the two to ensure sterility of the drug.

    Please let me know if you have further question.


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    Jingdong Zhu
    Independent Consultant
    Basking Ridge NJ
    USA
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    Original Message


  • 4.  RE: Aseptic and terminal sterilization

    This message was posted by a user wishing to remain anonymous
    Posted 19-Feb-2021 08:46
    This message was posted by a user wishing to remain anonymous

    From the FDA:

    " It is a well accepted principle that sterile drugs should be manufactured using aseptic processing ONLY when terminal sterilization is not feasible
    However, some final packaging may afford some unique and substantial advantage (e.g., some dual chamber syringes) that would not be possible if terminal sterilization were employed. In such cases, a manufacturer can explore the option of adding adjunct processing steps to increase the level of sterility assurance."
    NOTE: Similar position is also from the EU

    Original Message


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