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  • 1.  Combination product stability studies for PMA

    Posted 29-Apr-2018 07:20
    Dear Members,
    I have a case of a new combination product (the device is a type 3, manufactured in Europe) submitted for approval in US and Brazil. The MAH realised only the 25°C/60%HR stability study for both countries and the dossier was accepted by FDA (CDRH)  and ANVISA. I was expecting additional request for at least accelerated studies and for brazil the 30°C/75% results as described in ICH Q2 and WHO storage conditions. I went through all US requirements, but i could not find exception for combination products.   The MAH did not provid rational for not doing the other stability studies.
    Do you know which guidance will explain why you don't need to do all the stability studies?

    Thanks for your feedback
    Regards

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    Juliette Schenin-King
    Quality Auditor
    France
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  • 2.  RE: Combination product stability studies for PMA

    Posted 29-Apr-2018 07:33
    Hello,

    As per ICH, WHO & ASEAN Stability studies requirements, the stability studies conditions will vary depending on which Climatic Zone the stability data is submitted.

    These guidelines does not provide any references or explanation that stability studies need not be carried out in all Climatic zone conditions.
    However, this is a strategic filing decision and the manufacturer has to take a call depending on which countries they intend to get regulatory approvals and subsequently marketing the said product.

    Hope this helps !!

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    PURVI GORADIA
    Manager Regulatory Affairs
    Mumbai
    India
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    Original Message


  • 3.  RE: Combination product stability studies for PMA

    Posted 01-May-2018 12:28
    Quick question, what is the shelf life of this combination product? If the manufacturer is not claiming longer shelf life, also provided the excellent development stability studies data then evaluator may have waived the requirement.   It is at the discretion of the evaluator, I would think. I have seen examples not exactly like this, but similar scenarios.



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    Manda Pasarkar

    United States
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    Original Message


  • 4.  RE: Combination product stability studies for PMA

    Posted 30-Apr-2018 11:45
    Hi Juliette,

    I'll take a stab at the FDA process. When you say the dossier was accepted, do you mean accepted for review, or approved?

    Stability isn't required in 21 cfr 820, except under storage if the device deteriorates. (820.150). ICH Q2 applies to drugs, not devices. CDRH is going to review the PMA for review acceptance according to 814.20, which does not require ICH style stability. I can believe that CDRH would accept for review a PMA in the condition you described.

    Eventually there will be a substantive review and the drug constituent part of your combination product will be reviewed according to 21 CFR 4.4 (2)(vi) Thats where there may be a reviewer request for ICH stability studies of the drug. The actual requirements are in 211.166. I'd be worried about this moment, especially if there is no documented rational for not doing the full studies. The ICH conditions are not actually regulations, so it could be possible that for the specific circumstances of your PMA the 25/60 is sufficient. If by accepted you mean approved, then you dodged a bullet by having a unique product and robust 25/60. If by accepted you mean accepted for review, then stability questions may still come up.

    As a final thought, I'd look back at agency meeting minutes and see if stability was ever discussed. I'm assuming there was an IDE, so there should be years of background to the stability dossier. Honestly to think of a novel combination product PMA without extensive agency interaction is surprising.

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    Matthew Iorio, RAC
    United States
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    Original Message


  • 5.  RE: Combination product stability studies for PMA

    Posted 30-Apr-2018 13:44

    The concern is always the real-time study in the actual expected storage environment. The accelerated studies are typically used to estimate the real-time study, and are only useful if you don't have the real-time data yet. If you have the real-time data then the other studies aren't typically required.




    Original Message


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