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  • 1.  API site transfer

    Posted 16-Oct-2013 12:27
    Hi,

    Any guidance on the following scenario would be appreciated:

    ANDA for an injectable was in the process of being filed with US FDA. ANDA exhibit batch was manufactured using an API that is no longer being manufactured by the site because it is bought by another firm. New site for API manufacturing has not been identified. What would be the best course of action at this point?


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    Karan Dhaliwal
    RA Consultant
    United States
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  • 2.  RE:API site transfer

    Posted 17-Oct-2013 12:40

    My guess would be go ahead and submit the ANDA, Perhaps you would have to make addendum to the submission once new site is identified. Infact better course, to seek FDA input before submitting
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    Original Message


  • 3.  RE:API site transfer

    Posted 18-Oct-2013 13:55
    If you haven't identified the API manufacturer, you may get a refusal to file. I'd think that the API manufacturer would either have to be inspected or have a recent GMP inspection.  If you don't have the manufacturer identified, FDA will have no way to verify the compliance status of your API source.

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


  • 4.  RE:API site transfer

    Posted 28-Oct-2013 11:21
    A few thoughts-
    1. 1st, a reality check - reevaluate - is management absolutely sure it's worth seeking approval for this product? No matter which path is chosen, there is likely to be a serious delay (at least several months) vs. the original approval target, given this very late change in API sourcing.

    2. This looks like a 2-scenario situation.
    #1) Drop the current API and exhibit batch and start completely over with another API;
    #2) File the current ANDA as planned and use the review time to prepare exhibit batch(es) with a new alternate API. The new API version may be submitted as a major amendment if before approval, or, wait for post approval supplement. Major amendment is going to add 6-12 months to review.  After approval probably needs prior-approval supplement, and might take 1-2 yrs to approve, and that period starts after approval.

    3. IF management chooses to file the original ANDA anyway while working on alternate API - then many follow-up Q's need to be explored-
    >How much inventory exists from the "former" API site?
    >What is the exp dating or retest period of the existing API inventory?
    >Is the quantity + exp or retest date of existing API adequate to justify buying up existing API before it's gone?
    >If the new API site owner has no interest in this API, who would respond to CMC queries from OGD related to the API or its DMF?
    >Who would maintain the API DMF + pay DMF GDUFA establishment fees for the original API site if you go ahead and file the ANDA while working on an alternate API source?
    >The original API site may be subject to a pre-approval inspection (or may not need PAI, depending on what the new owners continue to do there). Would the new owners agree to host that?
    >For any completely new/alternate API to become qualified, assuming it would not be submittable until after June 2014, you will be running into the new OGD policy requesting at least 2 API batches + 3 finished dose batches to be produced & subjected to 6-month accelerated stability.

    Tough one. Unexpected buy-outs of key suppliers are very hard to plan for. One possible going-forward lesson might be to implement contracts with API suppliers that require them to support you in the event of "change of control" for at least 3 years.

    Hope that helps

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    Robert Falconer
    VP Technical Operations
    Breckenridge Pharmaceutical Inc.
    Henrico VA
    United States
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