Regulatory Open Forum

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  • 1.  DMF

    Posted 18-May-2014 22:01
    Hello,

    Can someone briefly explain what is the function of drug master file (DMF)? Also, what is the difference between a DMF and the mandatory CMC information submitted in a NDA application?

    Thank you!

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    Ranyang Li
    Process Development Engineer
    Tissuegene, Inc
    Rockville MD
    United States
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  • 2.  RE: DMF

    Posted 19-May-2014 10:55
    To add to Michael's response is the following Introduction from FDA's website on DMFs. Please refer to the Guideline for Drug Master Files which is very comprehensive.

    A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. The submission of a DMF is not required by law or FDA regulation. A DMF is submitted solely at the discretion of the holder. The information contained in the DMF may be used to support an Investigational New Drug Application (IND), a New Drug Application (NDA), an Abbreviated New Drug Application (ANDA), another DMF, an Export Application, or amendments and supplements to any of these.

    A DMF is NOT a substitute for an IND, NDA, ANDA, or Export Application. It is not approved or disapproved. Technical contents of a DMF are reviewed only in connection with the review of an IND, NDA, ANDA, or an Export Application.

    This guideline does not impose mandatory requirements (21 CFR 10.90(b)). It does, however, offer guidance on acceptable approaches to meeting regulatory requirements. Different approaches may be followed, but the applicant is encouraged to discuss significant variations in advance with FDA reviewers to preclude spending time and effort in preparing a submission that FDA may later determine to be unacceptable.

    Drug Master Files are provided for in 21 CFR 314.420. This guideline is intended to provide DMF holders with procedures acceptable to the agency for preparing and submitting a DMF. The guideline discusses types of DMF's, the information needed in each type, the format of submissions to a DMF, the administrative procedures governing review of DMF's, and the obligations of the DMF holder.

    DMF's are generally created to allow a party other than the holder of the DMF to reference material without disclosing to that party the contents of the file. When an applicant references its own material, the applicant should reference the information contained in its own IND, NDA, or ANDA directly rather than establishing a new DMF.


    All the best,

    Dar

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    Darlene Rosario
    Principal Consultant RA, Quality and Compliance
    Velocity Consulting
    Ventura CA
    United States
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    Original Message


  • 3.  RE: DMF

    Posted 19-May-2014 17:00
    A Drug Master File typically is filed by a firm that makes an active pharmaceutical ingredient (API) or an inactive ingredient that is purchased by a company that uses the API or inactive to manufacture a finished dosage form (FDF) product that requires either a NDA or ANDA approval.  In that situation, the FDF maker has a duty to include in its NDA/ANDA a description of how, in particular, the API is manufactured.  However, the API maker will not want the FDF maker to know how it makes the API as those processes are typically proprietary.  Thus, to allow the FDF maker to "include" the information on the API that it needs for its NDA/ANDA the API maker files a DMF with FDA and gives the FDF maker a letter providing a right of reference to the DMF, which the FDF maker includes in its application to satisfy its duty to describe how the API was made. 

    The information in the DMF often is very similar to what would have been included in the CMC section for the drug substance had the FDF maker also been the maker of the API.


    ______________________________________________
    Michael A. Swit, Esq.
    Special Counsel, FDA Law Practice
    Duane Morris LLP
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    Note: all postings by me on this forum represent my personal views and are not necessarily those of my clients or my law firm. Further, my comments are not intended as legal advice but as the sharing of general knowledge and do not create an attorney-client relationship with any reader.

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  • 4.  RE: DMF

    Posted 21-May-2014 14:26
    Michael,

    Thank you for your reply! It is very clear and helpful!

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    Ranyang Li
    Process Development Engineer
    Tissuegene, Inc
    Rockville MD
    United States
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    Original Message


  • 5.  RE: DMF

    Posted 22-May-2014 08:17

    In addition to excipients and API's there are additional DMF types for your reference

    The types of DMFs are:

    • Type II Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product

    • Type III Packaging Material

    • Type IV Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation

    • Type V FDA Accepted Reference Information


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      KELLY MILLER MS
      PAREXEL
      CLEARWATER FL
      United States
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      Original Message


  • 6.  RE: DMF

    Posted 22-May-2014 08:35
    Hi Ranyang.

    The purpose of the DMF is to allow the manufacturer of the drug active (or excipient) substance to provide essentially business confidential information to the FDA in a manner that allows the agency to fully evaluate the production methodology and any ancillary issues (possible impurities, etc.) that might arise from the production method.  Many companies are not comfortable with providing the required level of detail that would be found in a DMF to each and every finished product drug producer because of the fear of having the method duplicated and losing out not only on the sale of the ingredient to the company who duplicated (or had duplicated) the material but also by being undercut on price in the market generally.

    As several people have stated so much better than I probably could, the ingredient manufacturer then simply provides a "letter of access" or "letter of reference" to the finished product manufacturer allowing the FDA to utilize the information in the DMF in their review of the overall application.  This letter is inserted into the application in the position where the ingredient specific data is expected and would direct the agency to look at the DMF for the information that should be in that part of the CMC.  Without that letter, the FDA will require that the finished goods applicant provide full information on the raw active substance in its application.

    There is very little difference between the DMF and the CMC section of an application.  Essentially the difference is that the DMF deals specifically with the manufacturing of the active substance while the CMC deals more with the overall manufacturing of the finished product.

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    Victor Mencarelli
    Sr. Manager - Regulatory Affairs
    United States
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    Original Message