Part One: Signed Statements and Certification

Purpose:
Establish the submitter’s official GRAS conclusion and provide key identifying and administrative details of the submission.

Summary:
Part One must clearly state that the submitter concludes the ingredient is Generally Recognized as Safe (GRAS) under 21 CFR 570. Identify the ingredient, describe intended use and conditions of use, and include the proposed AAFCO ingredient definition. Provide formal certifications that the submission is complete, balanced, and includes all known favorable and unfavorable safety data. Include signatures from responsible officials to establish the legal and procedural foundation of the submission.

Focus:
Ensure declarations and certifications are properly signed and dated. Clearly identify the ingredient, intended use, and any limitations. Confirm that GRAS conclusion wording and the proposed AAFCO definition are concise and consistent throughout the submission. Use this section to demonstrate organizational accountability and procedural compliance.

Part Two: Identity, Method of Manufacture, Specifications, and Physical or Technical Effect

Purpose:
Establish the identity of the ingredient, how it is made, its characteristics, and its intended function.

Summary:
Part Two must describe ingredient identity, source materials, composition, and method of manufacture with sufficient detail to support safety evaluation. Include descriptions of raw materials, processing steps, and quality controls. Provide analytical specifications and representative batch data (typically three to five). Discuss potential contaminants or impurities, stability, and validation of analytical methods. 

Considerations:

• Manufacturing process: Provide a complete, labeled flow diagram and/or process description sufficient to evaluate consistency and safety. Additionally, provide reference(s) to peer-reviewed papers/books describing accepted manufacturing methods used to make ingredients.
• Specifications and contaminants: Provide analytical specifications supporting the guaranteed analysis and testing for potential contaminants (e.g., microbial, heavy metals, mycotoxins, pesticide residues). Explain why specific contaminants were included or excluded.

Focus:
Provide complete and reproducible manufacturing details. Ensure analytical methods are appropriate, validated, and relevant to safety. Identify potential impurities or by-products and provide rationale for specifications explaining how they ensure safety and consistency. Avoid unnecessary jargon unless it improves clarity or reproducibility.

Part Three: Target Animal and Human Exposures

Purpose:
Quantify expected exposure to the ingredient for target animals and, where applicable, for humans consuming animal-derived foods.

Summary:
Part Three should present quantitative exposure estimates for typical and maximum inclusion conditions. Include calculations or data for feed and drinking water exposures and, for food-producing animals, address potential residues in edible products (meat, milk, eggs). Discuss formation of by-products, degradation products, or metabolites that may influence exposure or safety.

Focus:
Provide transparent and well-referenced exposure calculations. State all assumptions, data sources, and conversion factors. Use recognized references (e.g., NRC tables, published models) where possible. Include both typical and worst-case scenarios and relate exposure estimates to intended use levels and margins of safety.

Part Four: Self-Limiting Levels of Use

Purpose:
Identify any natural or practical limits on inclusion rates for the ingredient.

Summary:
Part Four should document whether the ingredient exhibits self-limiting properties that restrict inclusion (for example, palatability issues, taste aversion, or physiological tolerance). If no self-limiting factors exist, provide a brief justification confirming that proposed use levels are practical and do not cause adverse responses.

Focus:
State explicitly whether self-limiting factors exist and provide supporting evidence or reasoning. Align this discussion with exposure estimates and proposed definition limits. If none are known, include a clear statement confirming that conclusion.

Part Five: Narrative

Purpose:
Provide the comprehensive safety rationale and interpretation of data from Parts Two through Four in support of the GRAS conclusion.

Summary:
Part Five is the scientific core of the submission. Integrate and interpret all relevant data to demonstrate safety under intended conditions of use. Explain how published and corroborative (unpublished) sources together support the GRAS conclusion. Address safety for target animals and humans, transparently discuss any conflicting or outlier data. The narrative should reflect general recognition of safety among qualified experts and rely primarily on publicly available evidence.

Considerations:

•  Narrative importance: Use the narrative to establish history of safe use and to connect empirical data to the GRAS conclusion.
• Safety over utility: GRAS guidelines focus on safety, not utility (except in rare cases where utility is directly tied to safety). Utility data can be used, but only to demonstrate that animal performance was not negatively impacted by the ingredient.

Focus:
Write a clear, logical narrative that connects all evidence to the GRAS conclusion. Reference supporting data rather than repeating it. Discuss uncertainties, data gaps, and mitigation steps. Distinguish between public and non-public data and weigh each appropriately in forming the safety conclusion.

Part Six: List of Supporting Data and Information

Purpose:
Compile and categorize all supporting materials cited throughout the submission.

Summary:
Part Six must list all references, reports, and data cited in the submission, clearly distinguishing publicly available from non-public information. Include full bibliographic citations and cross-reference each item to the relevant section(s). Provide copies of cited materials as appendices, organized alphabetically or by section for easy navigation.

• Publicly available, peer-reviewed information should form the backbone of the GRAS determination. Non-peer-reviewed or confidential data may support the narrative but are discouraged as the primary basis for a GRAS conclusion.

Focus:
Ensure every citation in the submission appears in this list and that references are consistently formatted. Confirm key safety data are publicly accessible. Cross-check appendices and narrative references for completeness and label appendices clearly for traceability.