FDA issues draft guidance for Dietary Ingredient Master File (NDIN MF)

The USFDA released draft guidance on New Dietary Ingredient Notification (NDIN) Master Files for dietary supplements in April 2024. Let’s break down what this means for the industry.

What are NDIs and NDINs?

• A New Dietary Ingredient (NDI) is any dietary ingredient not marketed in the U.S. in a dietary supplement prior to October 15, 1994.
• Before introducing a dietary supplement containing an NDI into interstate commerce, manufacturers or distributors must submit a New Dietary Ingredient Notification (NDIN) to the FDA at least 75 days in advance.
• The NDIN must demonstrate that the dietary supplement containing the NDI is reasonably expected to be safe.

Understanding NDIN Master Files

• An NDIN Master File is a repository of detailed information about the NDI’s identity, manufacturing process, and safety data.
• The Master File owner submits this file to the FDA for potential use in evaluating future NDINs.
• The Master File owner may grant written authorization to other parties to reference information from the NDIN Master File through a Letter of Authorization
• Both the owner and other authorized parties (e.g., business partners, manufacturers) can reference the Master File in their NDIN submissions.

How Does an NDIN Master File Work?

• The FDA doesn’t routinely review Master Files independently. They’ll review a Master File when an NDIN referencing it is submitted.
• If the FDA has questions about the Master File’s content, they’ll contact the Master File owner directly and also inform the notifier (of NDIN) of the general subject of the information needed without disclosing specific details about the NDIN Master File content. The notifier can either ask the Master File owner to supplement the NDIN Master File or otherwise provide the necessary information directly to FDA
• Master File owners have the responsibility to maintain and update their files as needed.
• NDIN Master Files are (preferably) submitted electronically via the CFSAN Online Submission Module (COSM) or ePortal.

NDIN Master Files vs. Drug Master Files (DMFs)

The NDIN Master File process draws similarities to the Drug Master File (DMF) process for drug products. Both streamline regulatory submissions by housing confidential ingredient details. Here are some key differences:

• Fees: No submission or review fees for NDIN Master Files (unlike DMFs).
• Templates: NDIN Master Files don’t have a standardized format (CTD) like DMFs.
• Annual Reports: NDIN Master File owners aren’t required to submit annual reports. However, they must promptly update the FDA of any changes to the file’s content.

USFDA Guidance: New Dietary Ingredient Notification Master Files for Dietary Supplements