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  • 1.  Impurity limit set up

    Posted 13-Nov-2018 06:13

    Dear Members,

    We are developing a Fixed Dose Combination (FDC) Tablet containing  Irbesartan and Amlodipine.

     As per literature data, The maximum daily dose of Irbesartan is 300 mg and for Amlodipine, it is  10 mg.

     As per ICH Q3B, Identification threshold for Amlodipine is 0.5%  (1 mg - 10 mg) & for Irbesartan it is 0.2%  (>10 mg - 2 g)                

    Please advise, for a combination product of Amlodipine and Irbesartan Tablet,  what would be the limit for Unidentified unspecified Impurity in Finished Product? Is it  0.2% or 0.5%

    Thanks in advance.



    ------------------------------
    Thanks & Best regards

    Rajib Kumar Baishnab
    Manager, Regulatory Affairs
    The ACME Laboratories Ltd.
    Dhamrai, Dhaka-1350, Bangladesh
    Ph: +8801990-407587
    Email: rbaishnab.qo@acmeglobal.com
    ------------------------------


  • 2.  RE: Impurity limit set up

    Posted 13-Nov-2018 12:56
    You should keep the tighter limit or you can justify the higher limit with available data.

    ------------------------------
    Gaurang Bhavsar, MS, RAC
    Manager, R&D and RA
    Sunrise Pharmaceutical, Inc.
    Rahway, NJ 07065
    USA
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    Original Message


  • 3.  RE: Impurity limit set up

    Posted 14-Nov-2018 03:53
    ​
    Hi Rajib Baishnab and Gaurang Bhavsar,

    Sorry its not like that, this is to inform you that we should keep the distinct acceptance criteria (Unidentified unspecified Impurity in DP) for both the individuals of Amlo (max 0.5 %) and Irbe (max 0.2 %) as per ICH Q3B. We shouldn't go for the combined limits to both the API's for the FCD.

    Regards
    VIJAY




    ------------------------------
    Vijay Yama
    Hyderabad
    India
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    Original Message


  • 4.  RE: Impurity limit set up

    This message was posted by a user wishing to remain anonymous
    Posted 19-Nov-2018 09:03
    This message was posted by a user wishing to remain anonymous

    Impurities on Impurities in combination products
    @https://www.tga.gov.au/book/182-related-impurities-drug-substances-and-drug-products 

    "18.2.2 Impurities in combination products

    If a drug product contains two or more drug substances, the limit for any identified impurity applies to the particular drug substance from which it is derived.

    The limit for an unidentified impurity should normally apply to whichever drug substance leads to the more stringent limit for the <g class="gr_ gr_19 gr-alert gr_gramm gr_inline_cards gr_run_anim Punctuation only-del replaceWithoutSep" id="19" data-gr-id="19">impurity,</g> unless it can be clearly demonstrated that the unidentified impurity was derived from a specific drug substance.

    The limit should take into account:

    • the maximum daily dose of each drug substance in the combination product
    • the likely overall patient exposure to the substance
    • the associated ICH limit for unidentified impurities
    • the content of each drug substance in the combination product".

    Original Message


  • 5.  RE: Impurity limit set up

    Posted 23-Nov-2018 04:20
    Dear All,
    Thanks a lot for all your valuable suggestions regarding setting up of impurity limit.

    ------------------------------
    Thanks & Best regards

    Rajib Kumar Baishnab
    Manager, Regulatory Affairs
    The ACME Laboratories Ltd.
    Dhamrai, Dhaka-1350, Bangladesh
    Ph: +8801990-407587
    Email: rbaishnab.qo@acmeglobal.com
    ------------------------------

    Original Message


  • 6.  RE: Impurity limit set up

    Posted 24-Nov-2018 02:46
    Dear Member,

           If we use two different method for the two API in the combination product for the determination of related substance, on that case 
    can we provide the acceptance limit for an unidentified impurity  for both API or not.

    Thanks in advance for your comment.

    ------------------------------
    MANOJ PANIGRAHI

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    Original Message


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