Regulatory Open Forum

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  • 1.  Filter Validation

    Posted 01-Aug-2013 12:27
    Can someone share his/her experience on the subject of  Filter validation requirement for an aseptically processed sterile product if one changes the manufacturing site.

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    Sunil Shah
    Spectrum Pharmaceuticals
    Irvine CA
    United States
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  • 2.  RE:Filter Validation

    Posted 02-Aug-2013 02:24
    Dear Sunil

    validation of an aseptic process includes filter validation. Replicaitng the process or moving the process to another site requires full revalidation of all elements of the process, including the filter.

    Regards
    Siegfried

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    Siegfried Schmitt
    Principal Consultant
    PAREXEL
    Braintree, Essex
    United Kingdom
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    Original Message


  • 3.  RE:Filter Validation

    Posted 04-Aug-2013 14:20
    While change in a fill site will certainly require revalidation using media fills, and any mixing and possibly hold time studies, you may not need to revalidate your filter.  Filter validation is frequently performed by the filter vendor at their site, and demonstrates that the filter retains organisms in the presence of your product matrix.  If you are using the same filter and there are no formulation changes, I'd argue that filter validation is site independent, and revalidation under these circumstances is not necessary.

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    Celeste Ramsey RAC
    Director, Regulatory Affairs
    Niwot CO
    United States
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    Original Message


  • 4.  RE:Filter Validation

    Posted 05-Aug-2013 05:49
    Dear Celeste
    thank you for your comments. The issue, I believe, is that there is no guarantee that filters are transported, stored, handled and used in the same way on either site. Neither is there any guarantee that the process conditions are identical and thus the filter may not perform in the same way as on th eprevious site.
    I think you'll be challenged by inspectors to perform filter re-validation
    Siegfried

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    Siegfried Schmitt
    Principal Consultant
    PAREXEL
    Braintree, Essex
    United Kingdom
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    Original Message


  • 5.  RE:Filter Validation

    Posted 06-Aug-2013 09:26

    Complex filter validation tests go beyond the capabilities of the filter user and such tests are often conducted by outside laboratories or by filter manufacturers. In such cases, filter validation experiments, including microbial challenges, need not be conducted in the actual manufacturing areas. However, it is essential that validation studies simulate actual production conditions. Validation data should be applicable to the user's products and conditions of use because filter performance may differ significantly for various conditions and products. Therefore, filter validation studies should be performed due to manufacturing site change to demonstrate there is no impact on pre- and post- filtration sterility in addition to the release product sterility specification.


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    Rajanikanth Bandaru PHD
    Somerset NJ
    United States
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    Original Message


  • 6.  RE:Filter Validation

    Posted 05-Aug-2013 10:14
    I don't completely agree.  Any aspects of the filter validation that may be site specific would have to be repeated, but if you are using the exact same filter (same manufacturer, same model number, etc.), there should be no need to repeat all of the filter validation studies.  The bubble point isn't going to change, the extractables profile isn't going to change, the microbial retention isn't going to change, etc.

    However, if it's not exactly the same filter, then you would need to provide the filter validation information for the new one, even if it's "equivalent" (same material of construction, same pore size, etc.).

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    Rachel Thornton
    Associate Director
    UCB
    Smyrna GA
    United States
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    Original Message


  • 7.  RE:Filter Validation

    Posted 05-Aug-2013 13:52
    Filter performance may differ significantly for various conditions and products.  

    The following factors may/can affect filter performance:

    (1) viscosity and surface tension of the material to be filtered
    (2) pH
    (3) compatibility of the material or formulation components with the filter itself
    (4) pressures
    (5) flow rates
    (6) maximum use time
    (7) temperature
    (8) osmolality
    (9) and the effects of hydraulic shock, etc.  

    When determining whether validation studies should be performed or not, please consider "the user's products and CONDITIONS OF USE."

    Document adequate "justifications."  

    Read the Guidance here.  
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    President and Principal
    http://www.regulatorydoctor.com
    Riner VA
    United States
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    Original Message


  • 8.  RE:Filter Validation

    Posted 06-Aug-2013 11:47
    Dear All,

    I very much appreciate everyone's thoughts and guidance on this subject. I see valid points on both the sides. However, it will be interesting to find out if FDA has accepted an application for a site change without filter re-validation based on the scietific rationale.

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    Sunil Shah
    Spectrum Pharmaceuticals
    Irvine CA
    United States
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    Original Message


  • 9.  RE:Filter Validation

    Posted 07-Aug-2013 09:26
    We have submitted a new Drug Substance manufacturing site for a biological product (mAb) with no filter validation at all, not even mention of it, and it was approved with no questions (on that topic).  This was in 2010.  Of course the normal process validation/PPQ lots were done, with the filter in place.  One caveat is that we do not claim sterility of the drug substance; don't know if that makes a difference.  I don't know if the subject came up at inspection as that was before my time.

    Looking at the data we normally submit for filter validation, both at my current company and previous ones, I fail to see how any of the studies would be impacted by the change in site.  The product is the same; the process is the same; the filter is the same.  Use of the filter in the process is validated as part of the overall process, but I don't include that under the heading of "filter validation".  As someone else mentioned, most of the filter validation studies are not even done at the site in question, but by a contractor or the filter supplier.

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    Rachel Thornton
    Associate Director
    UCB
    Smyrna GA
    United States
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    Original Message