GRAS PAS JC
Chemistry TG
Specifications of substances and raw materials Ad Hoc Group
February 11, 2016
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.
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In the absence of published specifications, specifications for raw materials, critical to
quality/safety, should be provided in the technical (GRAS) dossier. Required data elements for
the specification include:
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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 monograph on the raw material which may include, but is not limited to the following:
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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
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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
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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.
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