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  • 1.  Referencing API US-DMF in NDA applications for FDA

    This message was posted by a user wishing to remain anonymous
    Posted 09-Apr-2020 09:30
    This message was posted by a user wishing to remain anonymous

    Hi All, 
    I am looking for some advice on whether reference to US-DMF for an API supplier should be made in a NDA application if that particular API supplier will not be used commercially but has been used during drug development and manufacture of registration batches. 
     
    A bit of background to my question:

    An IR product was developed with API from supplier A. The process validation batches, stability batches and clinical batches of the drug product were all​ manufactured with the API from supplier A. Due to commercial reason, we will commercialize the drug product with API from supplier B. The API has a USP monograph, and the API from both supplier A and B are USP standard and will be controlled by the drug product manufacturer with identical specifications. The company intends to submit the drug application to the FDA for the drug product by referencing the API DMF from supplier B as part of the proposed commercial product and will not list API supplier A as commercial API supplier in the drug product application.

    In your opinion and based on your experience, should we also reference the DMF (and hence provide LOA) for supplier A?

    Has anyone had such experience? Any help on this matter would be very appreciated. 



  • 2.  RE: Referencing API US-DMF in NDA applications for FDA

    Posted 10-Apr-2020 07:38
    So if you never use API from.supplier B in you clinical trials or registration batches, only commercially, you should be discussing this with FDA ahead of time.   Your stability batches will need to be redone at a minimum, you may need equivalency justification of why they were not in clinical study use.or to do a bridging study.  But your application to FDA better include 6 months stability at a minimum with API B

    I worked on  project like this in early 2000s at 3M when the drug product's ownership, and manufacturing including API was going to be transferred in the middle of clinical development  at Phase 3/commercial. I was on the global Reg CMC team with partner company, and we had a very large F2F meeting with FDA.and the two companies,  as an issue based CMC meeting at EOP 2.

    My recommendation is not to do this without full disclosure/agreement up front in a meeting, as you really could put your stability and P3 study at risk.


    ------------------------------
    Ginger Cantor, MBA, RAC
    Founder/Principal Consultant
    Centaur Consulting LLC
    River Falls, Wisconsin 54022 USA
    715-307-1850
    centaurconsultingllc@gmail.com
    ------------------------------

    Original Message


  • 3.  RE: Referencing API US-DMF in NDA applications for FDA

    Posted 13-Apr-2020 15:47
    I would also submit DMF LOAs for both the old and new API's.  FDA may want to review old API DMF since you have a lot of drug product data (clinical batches) made with old API. You can confirm this if you have a F2F meeting with FDA as Ginger recommends.

    ------------------------------
    Tom
    Senior Director, Regulatory Affairs CMC
    Chicago
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    Original Message


  • 4.  RE: Referencing API US-DMF in NDA applications for FDA

    This message was posted by a user wishing to remain anonymous
    Posted 13-Apr-2020 15:49
    This message was posted by a user wishing to remain anonymous

    Hello,

    You will need to include the DMF LoA for Supplier A in the NDA since the batches used in your development program and clinical trial(s) were sourced from that supplier.

    For Supplier B, do not include their LoA in the NDA or list them in the 356h application form if they have not contributed to any API manufacturing during development.  Instead, in the original NDA or in a future submission (post-approval), you should include a comparability protocol that compares Supplier B to Supplier A and provides details on your proposed rationale for change (i.e., business reason or other), a risk assessment, equivalence of specs and data, etc.

    Two key FDA guidances are "Changes to an Approved NDA or ANDA" (April 2004) and "Comparability Protocols for Human Drugs and Biologics: Chemistry, Manufacturing, and Controls Information" (April 2016).

    Hope this helps!
    Original Message


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