"Provisional Monographs" for Self-Affirmed GRAS Ingredients

From FCC e-Newsletter (Summer 2009, Vol. 2, Issue 1)

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Within the U.S. regulatory food law, food ingredient manufacturers have several options to legally use food substances in food production. A popular option is the "GRAS Self-Affirmation" process, in which food manufacturers can follow a rigorous safety assessment of a proposed food substance and self-affirm the GRAS (Generally Recognized As Safe) status of such a substance using a panel of qualified experts. This process is exclusively the responsibility of the party seeking the self-affirmed GRAS status, and although the FDA does not register or review such claims it does recognize the status and allow for the legal use of self-affirmed GRAS ingredients in foods.

While this status has been recognized by the FDA since the proposed rule describing it was published in 1997, until now, the FCC has not had a mechanism specifically designed to establish monograph standards for food ingredients that have not undergone review by the FDA or other international regulatory authorities. To include a new food ingredient in the FCC, USP typically requests a statement of approval for the ingredient from a recognized regulatory authority, but such a notice from the FDA is not available for self-affirmed GRAS food ingredients. To include in the FCC food ingredients that are considered GRAS following such a self-affirmation procedure, USP offers now the newly developed provisional monograph process.

In general, the submission requirements for a provisional monograph do not differ from the requirements for a "standard" monograph. The following list indicates the most common requirements; however, this list will be modified depending on the nature of the food ingredient:

• A draft monograph for the ingredient, in the format of FCC monographs or information addressing the following required sections of an FCC monograph: Title, Synonyms, Chemical Structure, Chemical Formula, Formula Weight, CAS Number, INS Number (if applicable), FEMA Number (if applicable), Description, Functions (uses in foods), Packaging and Storage Information, Identification Tests (tests such as IR to aid in substantiating the identity of the ingredient), Assay (assay is a purity test to quantify the concentration of the principle component(s) in the ingredient), Impurities Tests (addressing potential organic and inorganic impurities that could occur in the product from raw materials or as a result of processing of the ingredient), and Specific Tests (or any test that does not clearly fit in other testing categories, including physical characteristics such as specific rotation, pH, loss on drying, etc.).
• Data from at least three food-grade batches of the ingredient which clearly indicate that the commercially available product meets all proposed specifications. Certificates of Analysis usually meet this requirement.
• Complete test methods for each test used in the monograph (unless the sponsor is using tests that already appear in FCC or USP-NF). If the test methods do not already appear in FCC or some compendial source, a validation report for each method. If non-FCC methods are used, a justification should also be provided. Additional information describing the required elements of method validation can be found in the FCC, 6th Edition.
• Any relevant regulatory information for the ingredient. This should include the regulatory authorities that have reviewed and approved the safety of this ingredient, and documentation to demonstrate this status. For provisional monographs, the summary of the self-affirmed GRAS report will have to be submitted in lieu of a statement by regulatory authorities.
• To aid USP scientific staff and the Food Ingredient Expert Committee in evaluating proposed specifications, relevant information on the method of manufacture and chemical composition of the food ingredients should be submitted where possible. Method of manufacture information should include the main ingredients and a description of the manufacturing process. Chemical compositional information should provide a characterization of the food ingredient sufficient to distinguish it from other similar food ingredients.

USP will also contact the sponsor for samples of any materials used in the proposed monograph as reference materials for potential development of a USP Reference Standard. USP encourages sponsors to provide an adequate quantity of each material, determined in consultation with USP staff, to facilitate future development and distribution.

A provisional monograph will be put through the same rigorous public vetting process as a standard monograph. USP will publish a specific section in the FCC that will contain all provisional monographs. However, if USP is informed that the food ingredient has been approved by the regulatory authorities during the provisional monograph development process or after its publication, USP will move the provisional monograph to the "standard" monograph section in FCC.

Please contact USP/FCC staff scientists to discuss in more detail.