Regulatory Open Forum

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  • 1.  Stability Testing- sample testing

    Posted 21-May-2014 04:02

    My question concerns whether it is mandatory to test one sample 3 times (per a test parameter) in stability testing as required in the validation testings.
    Reference to any published guidelines/regulations would be helpful (FDA/EU/ICH).

    Thank you.

    Sincerely,
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    Dahuin Lee
    Regulatory Affairs Associate
    Seoul
    Korea, Republic of
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  • 2.  RE: Stability Testing- sample testing

    Posted 21-May-2014 08:57
    Hi Dahuin.

    In my own experience it appears that you are referencing "accelerated" stability conditions.  The problem with testing 1 sample 3 times is that each time you remove the sample from the controlled atmosphere in the chamber, you change the dynamics of the tests.  What I have generally seen done is placing 3 samples in the chamber and removing one sample at each particular time point in order to ensure that you have the least impact on the data generated as possible.

    If this is for "real time" stability in your chosen environmental conditions, then there might be a reason for doing the same sample multiple times.  Just keep in mind that every time you open the sample, you increase your likelihood for microbial contamination (or any other type of contaminant in the area) and that could negatively impact your result as well.

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    Victor Mencarelli
    Sr. Manager - Regulatory Affairs
    United States
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  • 3.  RE: Stability Testing- sample testing

    Posted 22-May-2014 10:16
    The requirements for stability testing are linked to the standards to which you are claiming conformity.  You did not state what type of products.  If you are working with IVDs, here are a few standards to consider, depending upon the intended market:
    CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents
    EN 13640 Stability testing of in vitro diagnostic reagents
    ISO 23640 In vitro diagnostic medical devices - Evaluation of stability of in vitro diagnostic reagents

    Best of luck-
    Carole

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    Carole Harris RAC
    International Regulatory Program Manager
    Asuragen, Inc
    Austin TX
    United States
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  • 4.  RE: Stability Testing- sample testing

    Posted 23-May-2014 11:36
    Dahuin,

    Carole is correct in that it is difficult to give accurate input without more detail on the product type.  The testing of the number of samples or replicates on stability is dependent on many factors including the attribute being evaluated, method variability, product homogeneity among others.  Key is to generate a sampling plan justified scientifically to support your stability test plan to confirm stability throughout the proposed shelf life.  Typically more testing (replicates and sampling) is conducted early in the development program to understand the product where methods are typically minimally validate (Sensitivity, Linearity, Accuracy and Precision), however, full method validation should include evaluation of variability (lot to lot, sample to sample, laboratory, day to day, etc) including stack up tolerance and incorporate these into a sampling plan where the result can be relied on to represent that attribute.  I have typically tested Beginning, Middle and End samples for each attribute with sufficient replicates to understand the variability (statisticians are useful in this regard).  Then narrowed down replicates as justified by the data.  Again, all of this depends on your product, drug substance, versus drug product, IVD, etc.

    There are a number of ICH guidance documents on stability for drug products and Drug Substance but the level of detail on sampling and replicates needs to be justified by the developer/innovator. The Agencies do expect to know your sampling plan for the release of each batch to the market.

    Hope this is helpful, please feel free to connect if needed. rosariodar07@gmail.com,

    Dar

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    Darlene Rosario
    Principal Consultant RA, Quality and Compliance
    Velocity Consulting
    Ventura CA
    United States
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