Regulatory Open Forum

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  • 1.  Qualification/ Validation

    Posted 17-Oct-2020 07:41
    I am looking for guidance on appropriate level of qualification/ validation through different phases of Clinical Trials Phase1, 2, 3 and 4.
    Your expert advice is appreciated.
    Thank you.

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  • 2.  RE: Qualification/ Validation

    Posted 17-Oct-2020 07:44
    To be specific, request is for biologics.

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    Meena Garg
    Regulatory and QA Consultant, Vaccines
    Brampton ON
    Canada
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  • 3.  RE: Qualification/ Validation

    Posted 18-Oct-2020 10:18
    Hi Meena,

    Please clarify, 1) are you seeking guidance for validation of manufacturing process or analytical procedures or both? 2) biologics (I assume you refer to drugs not devices, right?), advanced therapies (e.g., gene and cellular therapeutics) vs proteins (E.g., mAbs, enzymes and cytokines) or both?


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  • 4.  RE: Qualification/ Validation

    Posted 18-Oct-2020 11:13
    Hello Jingdong,
    Please clarify, 1) are you seeking guidance for validation of manufacturing process or analytical procedures or both? Yes
    2) biologics (I assume you refer to drugs not devices, right?), advanced therapies (e.g., gene and cellular therapeutics) vs proteins (E.g., mAbs, enzymes and cytokines) or both? Yes, Including vaccines, not devices.
    Many thanks

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    Meena Garg
    Regulatory and QA Consultant, Vaccines
    Brampton ON
    Canada
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  • 5.  RE: Qualification/ Validation

    Posted 19-Oct-2020 09:14
    Process Validation: As described in the FDA & EMA guidelines on process validation, it's a continuous process that should be ongoing through the clinical phases, culminating in process performance qualification of your commercial process, and followed by continuous process verification after approval. For most markets, there is no expectation that any PPQ data would be submitted in a clinical trial application but is required in the marketing application. However, there is a strong preference for the commercial process to be used in your Ph3 trials, so PPQ is often performed just before or in parallel with Ph3. Even though the PPQ data is not required, many agencies want to see discussion of critical controls, particularly at Ph3. Also, validation of sterile or aseptic processes, or any non-standard processes, is required.

    Method Validation: Full method validation, in line with ICH guidance, is required in the marketing application. Earlier in development you should have some sort of qualification, if not full validation, just to be sure that you can trust the data your methods are giving you. A summary of that data should be included in the CTA. It's generally a good idea to have your methods fully validated before Ph3, and definitely before you run your PPQ batches, just because it's a huge risk to the company if you later find out that the method you used to generate all your Quality data is unreliable.

    The EMA guideline on requirements for the Quality information for a biotechnology product in the IMPD gives a good indication of what is expected when.

    Does that answer your question?

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    Rachel Thornton
    Associate Director
    Smyrna GA
    United States
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  • 6.  RE: Qualification/ Validation

    Posted 19-Oct-2020 09:55
    Dear Rachel, Thank you. This is clear and very helpful....
    Regards
    Meena

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    Meena Garg
    Regulatory and QA Consultant, Vaccines
    Brampton ON
    Canada
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  • 7.  RE: Qualification/ Validation

    Posted 19-Oct-2020 19:37
    Well said Rachael. 

    In some accelerated programs where phase 1/2 becomes the pivotal studies, there is some limited flexibility especially for analytical procedures validation. Case by case and may seek Agency's feedback or agreement as an option if the sponsor decides to do.

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