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  • 1.  US DMF Procedure

    Posted 20-Dec-2017 04:30
    ​Hi all,

    I must admit to being slightly confused by the US DMF guidance and procedure. The manufacturer of our API is now considered an external 3rd party- the same entity used to be considered an internal company. So while in the past Module 3.2.S sections have been provided, it is now appropriate to refer to a DMF. I am submitting a manufacturing transfer for the drug product which includes a minor change to the drug substance. In a European submission I would detail the changes and the justification for them. In the US, since there is no open (applicants) part of the DMF, is the only thing I need to provide the LOA without any further explanation regarding any changes or any supporting data since in theory I should be unaware that any changes have occurred?


    Kind Regards,

    David


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    David Cox
    United Kingdom
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  • 2.  RE: US DMF Procedure

    Posted 21-Dec-2017 10:32

    ​Hi David,

    The API manufacturer is obligated to notify you of the changes (see 21 CFR 314.420 (c)). While they don't have to provide all the details of the change, they should provide sufficient information to allow you to properly assess the impact on the Drug Product and drug product filing. If the change does not require a supplement on your part, then I think you can notify the FDA of the change during the next annual report. Otherwise a supplement should be submitted. Also see below from DMF guideline from FDA's website:

    "Any addition, change, or deletion of information in a DMF is required to be submitted to the DMF.  In addition the DMF holder must notify each person authorized to reference the DMF (authorized party) (See 21 CFR 314.420(c))  There are no reporting categories for DMFs.  All changes must be reported as amendments.  The DMF holder should notify each authorized party of the nature of the changes, providing as much detail as is consistent with the confidentiality agreement between the DMF holder and the authorized party, so that the authorized party can determine how to report the changes in their approved NDA or ANDA.  See 21 CFR 314.70 and related Guidances."

    Hope this helps.

    Sabrina


    Original Message


  • 3.  RE: US DMF Procedure

    Posted 21-Dec-2017 12:21

    For US, your API supplier (the DMF holder) should make you aware of any significant changes that are being made – ideally via a change control that you should be approving before they implement the change.  So you should have a general summary of the changes that are being made to the drug substance that you can include in your submission (i.e. cover letter) to FDA.  Then the LOA included in your submission will prompt FDA to review the DMF update.  It is a bit odd that up to this point you have been including drug substance info in 32S of your application and now you are switching to referencing a DMF, but I guess that's acceptable.  Even though there is now a DMF, you can still include the new info in 32S if the supplier is willing to share with you.  Just because they have a DMF doesn't mean you can't include the info in your application as opposed to referencing the DMF.

     

    Tom

    Chicago




    Original Message


  • 4.  RE: US DMF Procedure

    This message was posted by a user wishing to remain anonymous
    Posted 26-Dec-2017 09:20
    This message was posted by a user wishing to remain anonymous

    ​

    From the query it is not clear that which changes are made in US DMF or drug substance part, but below mentioned two variations has to be filed in US also.

    1. The manufacturing site transfer for finished drug product
    2. Change in drug substance

    Original Message


  • 5.  RE: US DMF Procedure

    This message was posted by a user wishing to remain anonymous
    Posted 26-Dec-2017 09:20
    This message was posted by a user wishing to remain anonymous

    ​DMF exists only for keeping the API information confidential for 3rd parties. If your API supplier has no problem sharing it with you the entire information or the justification for change and you wish to provide that information directly to the FDA, please go ahead, nothing stops you from doing it without sending the FDA the LOA to DMF.
    Original Message


  • 6.  RE: US DMF Procedure

    Posted 28-Dec-2017 00:38
    Dear David,

    Yes, you can always refer a DMF as I assume that DMF assessment fees paid and the DMF is on Active Status.
    But make sure the 3rd party has provided the necessary administrative ammendments to the US FDA.

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    Tushar Premchandani PHD
    Assistant Manager RA
    Olive Healthcare
    Daman
    India
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    Original Message


  • 7.  RE: US DMF Procedure

    This message was posted by a user wishing to remain anonymous
    Posted 13-Jun-2018 12:57
    This message was posted by a user wishing to remain anonymous

    Just to follow-up on the filing fee angle of this thread, when must a DMF hoder pay a filing fee?

    I'm thinking of a situation where a DMF for an investigational product that is not yet approved but the DMF has been filed by a contract manufacturer to protect some of its proprietary assets and then allows a customer to x-ref it for their IND. Its my understanding that a DMF for a commercially available API would incur a DMF filing fee but are there filing fees for a DMF for an investigational product? And what about a DMF for excipients only? Thanks in advance for any help.
    Original Message


  • 8.  RE: US DMF Procedure

    Posted 13-Jun-2018 20:48
    Filing fee for DMF Type II (API) exists only for generic ANDAs (GDUFA). No filing fee for IND stage products or for excipients.

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    GRSAOnline
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    Original Message


  • 9.  RE: US DMF Procedure

    Posted 14-Jun-2018 12:30

    Hi David

     

    To address your last question, I will add that DMF holder should be making you aware of any changes that are being made and your company should be signing off via your change control process on what the regulatory impact is.  This will enable you to describe the changes that are being made in your IND amendment while confidentiality is still maintained.  So you'll need to provide a little more than just a LOA for the DMF.  The change(s) can be summarized in either the cover letter or 1.11.1 Quality Information.  I typically use 1.11.1.

     

    Tom

    Chicago




    Original Message


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