Introduction:

Food additives are subject to FDA GRAS premarket review, but if a petitioner can show that an ingredient is Generally Recognized as Safe (GRAS) under its original conditions of use, then there is an exemption.

Writing a GRAS dossier can be a daunting process, but understanding the key elements and critical criteria for submission increases the likelihood of regulatory success for GRAS Dossiers. This overview covers exactly what you need to know about GRAS dossiers, to maximize your chances of submitting an effective dossier and the 7 parts of a GRAS dossier.

What is a GRAS Dossier?

A GRAS dossier is a regulatory submission that presents safety and efficacy data for a product containing an ingredient or combination of ingredients considered “generally recognized as safe” (GRAS). It includes scientific evidence from literature, peer-reviewed studies, and other research to support the determination that the ingredient is indeed safe for use in food products. The dossier also includes information about how the ingredient will be manufactured and used in food products.

What are the different parts of a GRAS Dossier?

You will require a GRAS dossier whether you’re planning for a self-affirmed GRAS or an FDA-notified GRAS. A GRAS dossier is a collection of papers that details the quality, safety, and efficacy of an ingredient. It is required to contain a substantial amount of data organized into seven key sections, including:

Part 1: Certified Claims and Signed Statements

Part 1 of a GRAS dossier must include details about the organization, the substance that was notified, the intended uses, and the rationale behind the GRAS conclusion. It must also include the signatures of an organization representative attesting to the information’s accessibility, accuracy, and confidentiality.

Section 2: Identity, Method of Manufacture, Specifications, and Physical or Technical Effect

Technical details about the substance, including its chemical name, empirical and structural formula, CAS number, physical and chemical properties, stability, and an in-depth account of the manufacturing process, are required in Part 2 of a GRAS dossier.

Part 3: Dietary Exposure

Based on data on food consumption in the United States, this part of a GRAS dossier considers the expected level of exposure to the substance from its intended use in addition to exposure from all dietary sources that may also contain the notified substance.

Part 4: Self-Limiting Levels of Use

In this section, the self-limited level of use of the substance must be discussed, if applicable. This is the limit to the amount of the ingredient that can be added to food before the product may become technologically unfeasible or unpalatable.

Part 5: Experience Based on Common Use in Food Before 1958

Most of the time, scientific methods will be used to back the GRAS conclusion’s underlying assumptions. However, if adequate historical data is given, the notifier has the option to support a substance’s GRAS status in part 5 of a GRAS dossier based on extensive previous use before January 1, 1958. GRAS conclusions based on widespread use are extremely uncommon because it is very challenging to locate supporting documentation of use previous to 1958.

Part 6: Narrative

A narrative supporting the foundation of the GRAS conclusion for the substance under its intended conditions of use must be included in Part 6 of the GRAS dossier. Any information that is incongruent with the GRAS conclusion must be addressed, and the narrative must include all of the substance’s information that is currently accessible. Unpublished studies may be used as supporting evidence, but publicly accessible safety data must form the bulk of the GRAS conclusion.

Part 7: List of Supporting Data and Information

All the information mentioned in Part 6 of the GRAS dossier that supports the substance’s safety must be given in Part 7, along with details on which information is public and which is unpublished.

What Supporting Data is needed for Analyzing the GRAS Dossier?

Once the applicant has determined what GRAS dossier information to submit, they must also choose which specific data to include. Applicants should consider both published and unpublished scientific references as well as proprietary studies to make sure they have sufficient data to support their safety and efficacy statements. All this data should be carefully analyzed by an experienced scientist or research group to come up with accurate conclusions that properly address all aspects of the evaluation.

What Documentation do you need to write for Section of the GRAS Dossier?

To ensure that your GRAS dossier submission is complete and accepted, it is important to provide robust documentation for each section included in the dossier. This documentation can include data gathered from published studies, tests performed on the product itself or on its ingredients, as well as any relevant information regarding any potentially toxic effects. All the documentation should be arranged logically in a way that clearly indicates the conclusions of each evaluation. Additionally, a detailed explanation should be given as to how various components of the product were chosen and why they are necessary.

How to finalize Your GRAS Dossier and Submit It for Review?

Once all the components of your dossier are in place and you have arranged them in a logical order, it is important to go through all the details one more time, triple-checking for accuracy and completeness. When everything is in order, you can submit the dossier to whatever agency or organization is necessary with confidence that they will accept it. Always ask if there is an electronic filing system, as this can allow you to track the progress of your submission while it’s being reviewed. Additionally, keep some hard copies available, as you may be asked to produce them at some point.