A Complete Guide to US FDA Regulatory Policy: Food Additives, GRAS, and Food Contact Substances

A Complete Guide to FDA Regulatory Policy: From Food Additives to GRAS

The US Food and Drug Administration (FDA) Data Standards Council is standardizing vocabulary across the entire FDA. As a result, the wording of some of the following terms may change slightly in the future.

Biotechnology

Refers to techniques scientists use to modify deoxyribonucleic acid (DNA) or the genetic material of microorganisms, plants, or animals to achieve desired traits. In terms of food, genetically modified plant-based foods are produced from crops whose genetic makeup has been altered through a process called recombinant DNA or gene splicing to confer desired traits on the plant. GM foods are also known as biotech, bioengineered, and transgenic, although "transgenic" can also refer to plant foods altered through methods such as conventional breeding. While biotechnology broadly refers to the technological application of biology, common usage in the US has narrowed the definition to foods produced using recombinant DNA. For more information, see the Biotechnology Program on the CFSAN internet site.

CEDI/ADI Database

For a large number of food contact substances, CFSAN maintains a database of Cumulative Estimated Daily Intakes (CEDI) and Acceptable Daily Intakes (ADI). CEDIs and ADIs are based on currently available information and may be revised when information is submitted or made available. The CEDI/ADI database is updated approximately twice a year. CEDIs and ADIs are based on currently available information and may be revised based on new information submitted to OFAS.

Color Additives

A color additive is a dye, pigment, or other substance that imparts color when added or applied to food, drugs, cosmetics, or the human body. The legal definition can be found in Section 201(t) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which also provides exceptions. Color additives used in food, drugs, and cosmetics require premarket approval. Color additives used in or on medical devices require premarket approval if they come into direct contact with the human body for an extended period. For more information, see the Color Additives Program on the CFSAN internet site.

Colorant

A colorant is a dye, pigment, or other substance used to impart color to, or alter the color of, a food contact material, but which does not migrate into food in amounts that would visibly impart any color to the food. The term "colorant" includes substances such as optical brighteners and fluorescent whitening agents, which may not themselves be colored but whose use is intended to affect the color of the food contact material. (21 CFR 178.3297(a)).

EAFUS

The "Everything Added to Food in the United States" (EAFUS) database is an information database maintained by CFSAN under an ongoing program called the Priority-based Assessment of Food Additives (PAFA). PAFA contains administrative, chemical, and toxicological information on more than 2,000 substances added directly to food, including direct food additives regulated by the FDA, secondary direct food additives, color additives, GRAS, and prior-sanctioned substances. Additionally, the database contains only administrative and chemical information for about 1,000 such substances. For information on more than 3,000 EAFUS substances, please refer to the EAFUS list.

Food Additives

A food additive is defined in Section 201(s) of the FD&C Act as any substance whose intended use directly or indirectly results, or may reasonably be expected to result, in its becoming a component of any food or otherwise affecting the characteristics of any food (including any substance intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or storing food; and including any source of radiation intended for any such use); if the substance was not subject to GRAS or sanction prior to 1958, or is not otherwise excluded from the definition of a food additive.

Food Contact Substance (FCS)

Section 409 of the FD&C Act defines a food contact substance as any substance intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food, provided that the use of the substance is not intended to have any technical effect on such food. For more information, visit the Food Contact Substance Notification Program page.

There is a hierarchy from Food Contact Substance (FCS) to Food Contact Material (FCM) to Food Contact Article (FCA).

A food contact substance (the subject of a food contact notification) is a single substance, such as a polymer or an antioxidant within a polymer. As a substance, it is relatively pure (a chemist's definition of a substance). Even though a polymer may consist of several monomers, it still has a well-defined composition.

A food contact material (FCM) is made from an FCS and (usually) other substances. It is typically (but not necessarily) a mixture, such as an antioxidant within a polymer. Its composition can be variable.

A food contact article is a finished film, bottle, dough hook, tray, or any article formed from an FCM.

GRAS

"GRAS" is an acronym for the phrase Generally Recognized As Safe. Under Sections 201(s) and 409 of the FD&C Act, any substance intentionally added to food is a food additive requiring premarket review and approval by the FDA, unless the substance is generally recognized among qualified experts as safe under the conditions of its intended use, or unless the use of the substance is exempt from the definition of a food additive. GRAS substances are distinguished from food additives by the type of information that supports the GRAS conclusion — namely, that it is publicly available and generally accepted by the scientific community, but should be of the same quantity and quality as the information that would support the safety of a food additive. For more information on GRAS, visit the GRAS Notification Program page.

Guidance Documents

Guidance documents are documents prepared for FDA staff, applicants/sponsors, and the public that describe the agency's interpretation of, or policy on, a regulatory issue. Guidance documents include, but are not limited to, documents related to the design, production, labeling, promotion, manufacturing, and testing of regulated products; the processing, content, and evaluation or approval of submissions; and inspection and enforcement policies. Guidance documents are not legally binding on the public or the FDA, nor do they establish legally enforceable rights or responsibilities. They represent the agency's current thinking. (21 CFR 10.115). A complete list of CFSAN guidance documents is available on the internet.

Indirect Food Additives

Generally, these food additives come into contact with food during packaging, holding, or processing, but are not intended to be added directly to food, become an ingredient, or have a technical effect in or on the food. Indirect food additives for food contact articles referenced in Title 21 of the US Code of Federal Regulations (21 CFR) include adhesive and coating components (Part 175), paper and paperboard components (Part 176), polymers (Part 177), and adjuvants and production aids (Part 178). Currently, other indirect food additives are authorized through the Food Contact Notification Program. Additionally, indirect food additives may be authorized under 21 CFR 170.39.

PAFA

The Priority-based Assessment of Food Additives (PAFA) database is a database that serves as CFSAN's institutional memory for the toxicological effects of food ingredients known to be used in the US. Currently, PAFA contains oral toxicology information for more than 2,100 of the approximately 3,300 direct food ingredients used in US foods. PAFA also contains minimal information on more than 3,200 indirect additives, including names, CAS numbers, and regulatory information for indirect additives in the Code of Federal Regulations. The EAFUS list and indirect additive list on the CFSAN internet site consist of selected information fields generated from PAFA.

Prior-Sanctioned Substances

A letter issued by the FDA or USDA stating no objection to a substance for a specific use, the use of which in or on food is the subject of the letter. Prior sanctions apply only to substances for specific uses in food that were explicitly approved by the FDA or USDA before September 6, 1958, at the levels, conditions, and products determined. Some prior-sanctioned substances are codified in 21 CFR Part 181.

SCOGS Reports

"SCOGS" is an acronym for the Select Committee on GRAS Substances. Beginning in 1972, under contract with the FDA, the Life Sciences Research Office of the Federation of American Societies for Experimental Biology convened a select committee that independently conducted a comprehensive review of the safety and health aspects of GRAS food substances on the FDA's then-proposed GRAS list. The select committee published its evaluations in a series of reports called SCOGS reports. The opinions and conclusions of 115 SCOGS reports published between 1972 and 1980 are listed on the CFSAN internet site.

Secondary Direct Food Additives

This term is found in the heading of 21 CFR 173, a regulation created during the 1977 reorganization of food additive regulations. Secondary direct food additives have a technical effect on food during processing but have no technical role in the finished food (such as processing aids). Some secondary direct food additives also meet the definition of a food contact substance. For more information on food contact substances, see the Food Contact Substance Notification Program.

Threshold of Regulation (TOR) Exemption

If a substance used in a food contact article has been shown to meet the requirements of 21 CFR 170.39, the substance may be exempted from the requirements of food additive listing regulations. For details, see 21 CFR 170.39. For a complete list of TOR exemptions, see the Threshold of Regulation list on the CFSAN internet site.