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GRAS PAS Task Group - Chemistry Raw Materials and Substance subject to GRAS notification/self-GRAS 1. Definition: Raw materials are substances used in the manufacturing process of the proposed GRAS substance and which undergo further transformational changes and/or purification. Substances intentionally added to the product formulation at the final stages of the manufacturing process wherein no further transformational change/purification occurs are outside the scope of this definition. Such substances will be referred to as ‘sub-components’. 2. Identity: All raw materials used should be identified, described and/or characterized as appropriate to their intended use in the manufacturing process. 3. Intended use: A raw material may be introduced at any point during the manufacturing process for specific technological purposes. The technological function and point of introduction should be identified/described in the manufacturing section of the technical (GRAS) dossier. 4. Specifications: The specification requirement for each raw material should be appropriate for its intended use, its point of introduction into the process and the presence/absence of downstream processes to further transform and/or to reduce/eliminate harmful impurities and contaminants. A raw material does not have to be food grade or cleared for use in foods as a GRAS ingredient/food additive. However, any raw material that is expected to have an impact on the safety and quality of the proposed GRAS substance should be identified, along with the critical to safety/quality parameter(s) and relevant control measures/criteria and limits. If published specifications for the raw material are available, for example in the Food Chemicals Codex (FCC), these should be cited and appropriately referenced. In the absence of published specifications, specifications for critical to quality/safety raw materials should be provided in the technical (GRAS) dossier. Required data elements for the specification include: Substance identity/descriptor (see section below for examples of data elements that may be used to define raw material identity) Identification/description of critical test parameter(s) & method(s) and acceptance criteria Test results/certificates of analysis showing conformance to acceptance criteria Raw Materials: Raw material need not be generally recognized as safe or approved food additives, but steps should be taken to ensure the correct identities of the raw materials are provided. The following information should be provided: A comprehensive monograph on the raw material which includes the following: Recognized common or non-proprietary name of the raw material (for example, names appearing in the Food Chemicals Codex (FCC) and names used by the Joint Food and Agriculture Organization of the United Nations / World Health Organization Expert Committee on Food Additives (JECFA), the U.S. and British Pharmacopoeia, the National Formulary, etc.). Where applicable, o The chemical name, following the International Union of Pure and Applied Chemistry (I.U.P.A.C.) rules of nomenclature, should be supplied. o Also, the Chemical Abstracts Service (CAS) registry, the International Numbering System (INS) number, the Color Index (CI) number in the case of colors and/or the Enzyme Commission (E.C.) number in the case of enzymes should be indicated. o Any trade or brand names or suggested named assigned to the raw material For a chemical raw material, the following needs to be provided: o Empirical formula o Structural formula o Molecular formula and molecular weight o When there is no structural formula applicable, a means of identification to characterize the composition should be provided. For plants, the genus and species should be provided in accordance with the International Code of Botanical Nomenclature for algae, fungi and plants o Provide clarity on the part of the plant being used For animals, the genus and species should be provided in accordance with the International Commission/Code of Zoological Nomenclature o Provide clarity on the part of the animal being used For enzymes, the type of enzyme, if known, and the source of the enzyme and the name of the enzyme should be provided in accordance with the International Union of Biochemistry and Molecular Biology on the nomenclature and classification of enzymes o Enzyme Commission number, if available should be provided as a reference For micro-organisms, the name should be provided in accordance with the International Code of Nomenclature of Bacteria Impurities such as arsenic, heavy metals, lead etc. should be disclosed Further details on the raw material may also be provided: o Form – solid, liquid(e.g. sap of a plant), gas o Stability at room temperature o Solubility, if applicable Substance Subject to GRAS Notification or Self-GRAS: A comprehensive monograph on the substance subject to GRAS notification or self-GRAS should be provided to ensure correct characterization of the substance. This should include, but not limited to, the following: 1. Recognized common or non-proprietary name of the substance (for example, names appearing in the Food Chemicals Codex (FCC) and names used by the Joint Food and Agriculture Organization of the United Nations / World Health Organization Expert Committee on Food Additives (JECFA), the U.S. and British Pharmacopoeia, the National Formulary, etc.). 2. Where applicable, a. The chemical name, following the International Union of Pure and Applied Chemistry (I.U.P.A.C.) rules of nomenclature, should be supplied. b. Also, the Chemical Abstracts Service (CAS) registry, the International Numbering System (INS) number, the Color Index (CI) number in the case of colors and/or the Enzyme Commission (E.C.) number in the case of enzymes should be indicated. 3. Any trade or brand names or suggested named assigned to the raw material and the rationale for it should be provided 4. For a chemical substance, the following needs to be provided: a. Empirical formula b. Structural formula c. Molecular formula and molecular weight d. Nuclear Magnetic Resonance spectrum, Mass spectrometry and Chromatographic analysis e. When there is no structural formula applicable, e.g., mixtures, a means of identification to characterize the final composition should be provided. f. Impurities such as arsenic, heavy metals, lead etc. and appropriate purification steps should be disclosed g. Provide form – solid, liquid, gas, semi-solid h. Stability at room temperature i. Solubility, if applicable j. Any other certificate of analysis 5. Manufacturing/processing considerations that could impact the final composition of the substance should be called out a. This is especially relevant for mixtures, blends or fermented products 6. When possible, a detailed manufacturing flow diagram should be provided to show the traceability and authenticity of the material from growth, production/source 7. Any safety hazards related to carry-over contaminants and a process to mitigate that should be provided 8. Consideration of general critical quality parameters to ensure that the quality of the produced is consistent 9. For enzymes, a. Provide enzyme identity confirmation by demonstrating that the experimentally determined primary amino acid sequence matches the predicted primary amino acid sequence b. Provide mass purity which refers to the percentage of the protein in a preparation that is the target enzyme or protein. c. Provide enzymatic purity or activity purity which refers to the fraction of activity observed in an assay that comes from a single enzyme. Typically, if 100% (or nearly so) of the observed activity in an enzyme assay is derived from a single enzyme then the enzyme preparation is considered enzymatically pure, even if it lacks mass purity. 10. For micro-organisms, the name should be provided in accordance with the International Code of Nomenclature of Bacteria a. The strain identification should be performed by phenotypic tests followed by genetic identification with methods such as DNA/RNA hybridization and 16sRNA sequencing and/or species-specific polymerase chain reaction (PCR) b. Indicate if the strain was genetically modified 11. A list of all pertinent publications related to the production process and its adaptation from previous GRAS notifications as applicable to the substance as a reference database. NOTE: Some ingredients (e.g., enzymes, polymers, botanical substances) could require additional information. This will be provided later. Submitted: PA Marone December 10, 2015