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`Federal Register / Vol. 62, No. 74 / Thursday, April 17, 1997 / Proposed Rules
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`DEPARTMENT OF HEALTH AND
`HUMAN SERVICES
`Food and Drug Administration
`21 CFR Parts 170, 184, 186, and 570
`[Docket No. 97N–0103]
`Substances Generally Recognized as
`Safe
`AGENCY: Food and Drug Administration,
`HHS.
`ACTION: Proposed rule.
`SUMMARY: The Food and Drug
`Administration (FDA) is proposing to
`clarify the criteria for exempting the use
`of a substance in human food or in
`animal feed from the premarket
`approval requirements of the Federal
`Food, Drug, and Cosmetic Act (the act)
`because such use is generally
`recognized as safe (GRAS). FDA is also
`proposing to replace the current GRAS
`affirmation process with a notification
`procedure whereby any person may
`notify FDA of a determination that a
`particular use of a substance is GRAS.
`Under the proposed notification
`procedure, the agency intends to
`evaluate whether the submitted notice
`provides a sufficient basis for a GRAS
`determination and whether information
`in the notice or otherwise available to
`FDA raises issues that lead the agency
`to question whether use of the substance
`is GRAS. This proposal reflects FDA’s
`commitment to achieving the goals for
`the Reinventing Food Regulations part
`of the President’s National Performance
`Review (hereinafter referred to as
`Reinventing Food Regulations). The
`proposed notification procedure would
`allow FDA to direct its resources to
`questions about GRAS status that are a
`priority with respect to public health
`protection.
`DATES: Written comments by July 16,
`1997, except that comments regarding
`information collection should be
`submitted by May 19, 1997. The agency
`proposes that any final rule that may
`issue based on this proposal become
`effective 60 days after its date of
`publication.
`ADDRESSES: Submit written comments
`to the Dockets Management Branch
`(HFA–305), Food and Drug
`Administration, 12420 Parklawn Dr.,
`rm. 1–23, Rockville, MD 20857. Submit
`written comments on the information
`collection requirements to the Office of
`Information and Regulatory Affairs,
`Office of Management and Budget
`(OMB), New Executive Office Bldg., 725
`17th St. NW., rm. 10235, Washington,
`DC 20503, ATTN: Desk Officer for FDA.
`
`FOR FURTHER INFORMATION CONTACT:
`Regarding Human Food Issues: Linda S.
`Kahl, Center for Food Safety and
`Applied Nutrition (HFS–206), Food
`and Drug Administration, 200 C St.
`SW., Washington, DC 20204, 202–
`418–3101.
`Regarding Animal Feed Issues: George
`Graber, Center for Veterinary
`Medicine (HFV–220), Food and Drug
`Administration, 7500 Standish Pl.,
`Rockville, MD 20855, 301–594–1731.
`SUPPLEMENTARY INFORMATION:
`Table of Contents
`I. Background
`A. The 1958 Amendment
`B. History of FDA’s Approach to the GRAS
`Exemption
`1. The GRAS List
`2. Opinion Letters
`3. Agency-initiated GRAS Review
`4. GRAS Criteria and the GRAS
`Affirmation Process
`5. The Plant Policy Statement
`C. Elements of the GRAS Standard
`D. The GRAS Petition Process
`II. Scope of the Proposed Regulations
`III. Proposed Revisions to § 170.30—
`Eligibility for Classification as GRAS
`A. General Criteria
`B. Scientific Procedures GRAS
`Determination
`1. Establishing General Recognition of
`Safety
`2. Corroboration of Safety
`C. Common Use GRAS Determination
`D. Other Provisions of Current § 170.30
`IV. The Technical Element of a GRAS
`Determination Through Scientific
`Procedures
`A. Consideration of Dietary Exposure
`B. Substantial Equivalence to a GRAS
`Substance
`V. Proposed Revisions to § 170.35—
`Affirmation of GRAS Status
`VI. Proposed Establishment of a Notification
`Procedure
`A. General Requirements
`B. Specific Requirements
`1. GRAS Exemption Claim
`2. Identity and Specifications
`3. Self-limiting Levels of Use
`4. Scientific Procedures GRAS
`Determination
`5. Common Use GRAS Determination
`C. Agency Response
`1. Acknowledgment of Receipt
`2. 90-day Response Letter
`3. Subsequent Agency Action
`D. Appeals
`E. Public Disclosure and Accessibility
`1. Public Disclosure
`2. Public Accessibility
`F. Inventory
`VII. Effect of the Proposed Notification
`Procedure on Existing GRAS Petitions
`VIII. Interim Policy
`IX. Conforming Amendments
`X. International Harmonization
`XI. Food Substances Used in Animal Feed
`XII. Summary of the Proposal
`XIII. Paperwork Reduction
`XIV. Analysis of Impacts
`
`A. Regulatory Options
`B. Costs and Benefits
`1. Option One: Take No Action
`2. Option Two: Adopt Proposed GRAS
`Notification Procedure
`3. Option Three: Adopt a GRAS
`Notification Procedure Allowing FDA
`Feedback on Independent GRAS
`Determinations of Either a Higher or
`Lower Level of Authoritativeness than
`the Proposed Notification System
`4. Option Four: Eliminate Agency
`Participation in Independent GRAS
`Determinations
`C. Regulatory Flexibility Analysis
`D. Conclusions
`XV. Environmental Impact
`XVI. References
`I. Background
`A. The 1958 Amendment
`In 1958, in response to public concern
`about the increased use of chemicals in
`foods and food processing and with the
`support of the food industry, Congress
`enacted the Food Additives Amendment
`(the 1958 amendment) to the act. The
`basic thrust of the 1958 amendment was
`to require that, before a new additive
`could be used in food, its producer
`demonstrate the safety of the additive to
`FDA. The 1958 amendment defined the
`terms ‘‘food additive’’ (section 201(s) of
`the act (21 U.S.C. 321(s))) and ‘‘unsafe
`food additive’’ (section 409(a) of the act
`(21 U.S.C. 348(a))), established a
`premarket approval process for food
`additives (section 409(b) through (h)),
`and amended the food adulteration
`provisions of the act to deem
`adulterated any food that is, or bears or
`contains, any food additive that is
`unsafe within the meaning of section
`409 (section 402(a)(2)(C) of the act (21
`U.S.C. 342(a)(2)(C))).
`Congress recognized that, under this
`scheme, the safety of an additive could
`not be established with absolute
`certainty, and thus provided for a
`science-based safety standard that
`requires producers of food additives to
`demonstrate to a reasonable certainty
`that no harm will result from the
`intended use of an additive (Ref. 1).
`FDA has incorporated this safety
`standard into its regulations (§ 170.3(i)
`(21 CFR 170.3(i))). If FDA finds an
`additive to be safe, based ordinarily on
`data submitted by the producer to the
`agency in a food additive petition (FAP),
`the agency issues a regulation specifying
`the conditions under which the additive
`may be safely used.
`In enacting the 1958 amendment,
`Congress recognized that many
`substances intentionally added to food
`would not require a formal premarket
`review by FDA to assure their safety,
`either because their safety had been
`established by a long history of use in
`
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`Federal Register / Vol. 62, No. 74 / Thursday, April 17, 1997 / Proposed Rules
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`food or by virtue of the nature of the
`substances, their customary or projected
`conditions of use, and the information
`generally available to scientists about
`the substances. Congress thus adopted,
`in section 201(s) of the act, a two-step
`definition of ‘‘food additive.’’ The first
`step broadly includes any substance, the
`intended use of which results or may
`reasonably be expected to result,
`directly or indirectly, in its becoming a
`component or otherwise affecting the
`characteristics of food. The second step,
`however, excludes from the definition
`of ‘‘food additive’’ substances that are
`generally recognized, among experts
`qualified by scientific training and
`experience to evaluate their safety
`(‘‘qualified experts’’), as having been
`adequately shown through scientific
`procedures (or, in the case of a
`substance used in food prior to January
`1, 1958, through either scientific
`procedures or through experience based
`on common use in food) to be safe
`under the conditions of their intended
`use.
`Importantly, under section 201(s) of
`the act, it is the use of a substance,
`rather than the substance itself, that is
`eligible for the GRAS exemption. In
`addition, it is well settled that a mere
`showing that use of a substance is
`‘‘safe’’ is not sufficient to exempt the
`substance from the act’s definition of
`‘‘food additive’’ (United States v. An
`Article of Food * * * Coco Rico, Inc.,
`752 F.2d 11, 15 n. 4 (1st Cir. 1985)).
`Instead, the substance must be shown to
`be ‘‘generally recognized’’ as safe under
`the conditions of its intended use (Id.;
`United States v. Articles of Food and
`Drug * * * Coli-Trol 80, 518 F.2d 743,
`745 (5th Cir. 1975)). The proponent of
`the exemption has the burden of
`proving that the use of the substance is
`‘‘generally recognized’’ as safe (Id). To
`establish such recognition, the
`proponent must show that there is a
`consensus of expert opinion regarding
`the safety of the use of the substance.
`(See United States v. Western Serum
`Co., Inc., 666 F.2d 335, 338 (9th Cir.
`1982); United States v. Articles of Drug
`* * * Promise Toothpaste, 624 F.Supp.
`776, 778 (N.D. Ill. 1985), aff’d 826 F.2d
`564 (7th Cir. 1987); United States v.
`Articles of Drug * * * Hormonin, 498
`F.Supp.2d 424, 435 (D.N.J. 1980).)
`Unanimity among experts regarding
`safety of a substance is not required.
`(See United States v. Articles of Drug
`* * * 5,906 boxes, 745 F.2d 105, 119 n.
`22 (1st Cir. 1984); United States v. An
`Article of Drug * * * 4,680 Pails, 725
`F.2d 976, 990 (5th Cir. 1984); Coli-Trol
`80, supra, 518 F.2d at 746; Promise
`Toothpaste, supra, 624 F.Supp. at 782.)
`
`However, the existence of a severe
`conflict among experts regarding the
`safety of the use of a substance
`precludes a finding of general
`recognition (4,680 Pails, supra, 725 F.2d
`at 990; Premo Pharmaceutical
`Laboratories v. United States, 629 F.2d
`795, 803 (2d Cir. 1980)) (Cf. Coli-Trol
`80, supra, 518 F.2d at 746 (mere conflict
`among experts is not enough to preclude
`a finding of general recognition)).
`It is on the basis of the GRAS
`exemption to the food additive
`definition that many substances (such as
`vinegar, vegetable oil, baking powder,
`and many salts, spices, flavors, gums,
`and preservatives) are lawfully
`marketed today without a food additive
`regulation. Under the 1958 amendment,
`a substance that is GRAS for a particular
`use may be marketed for that use
`without agency review and approval.
`However, when a use of a substance
`does not qualify for the GRAS
`exemption or other exemptions
`provided under section 201(s) of the act,
`that use of the substance is a food
`additive use subject to the premarket
`approval mandated by the act. In such
`circumstances, the agency can take
`enforcement action to stop distribution
`of the food substance and foods
`containing it on the grounds that such
`foods are or contain an unlawful food
`additive.
`Importantly, under section 201(s) of
`the act, the GRAS exemption applies to
`the premarket approval requirements for
`food additives only. There is no
`corresponding exemption to the
`premarket approval requirements for
`color additives, which are defined in
`section 201(t) of the act.
`B. History of FDA’s Approach to the
`GRAS Exemption
`1. The GRAS List
`Shortly after passage of the 1958
`amendment, FDA clarified the
`regulatory status of a multitude of food
`substances that were used in food prior
`to 1958 and amended its regulations to
`include a list of food substances that,
`when used for the purposes indicated
`and in accordance with current good
`manufacturing practice, are GRAS. This
`list was incorporated into the agency’s
`regulations as § 121.101(d) (now parts
`182 and 582 (21 CFR parts 182 and 582))
`(24 FR 9368, November 20, 1959). As
`part of that rulemaking, however, FDA
`acknowledged that it would be
`impracticable to list all substances that
`are GRAS for their intended use
`(formerly § 121.101(a); current
`§ 182.1(a)).
`Section 121.101(d) became commonly
`referred to as ‘‘the GRAS list.’’ FDA
`
`added other categories of substances
`(e.g., spices, seasonings, and flavorings)
`to the GRAS list in subsequent
`rulemakings (25 FR 404, January 19,
`1960; and 26 FR 3991, May 9, 1961).
`2. Opinion Letters
`Many substances that were
`considered GRAS by the food industry
`were not included in the agency’s GRAS
`list. Under the 1958 amendment, a
`substance that is GRAS for a particular
`use may be marketed for that use
`without agency review and approval.
`Nonetheless, as a practical matter,
`manufacturers who determined on their
`own initiative that use of a substance
`qualified for the GRAS exemption
`frequently decided to obtain the
`agency’s opinion on whether their
`determination was justified. Many
`manufacturers wrote to FDA and
`requested an ‘‘opinion letter,’’ in which
`agency officials would render an
`informal opinion on the GRAS status of
`use of a substance. Although convenient
`and expedient, these opinion letters
`were often available only to the
`requestor. Moreover, these opinion
`letters were not binding on the agency
`at the time they were issued and were
`in fact formally revoked in 1970 (21 CFR
`170.6, 35 FR 5810, April 9, 1970).
`3. Agency-Initiated GRAS Review
`In 1969 (34 FR 17063, October 21,
`1969), FDA removed various cyclamate
`salts, a family of nonnutritive
`sweeteners, from the GRAS list because
`they were implicated in the formation of
`bladder tumors in rats (Ref. 2). In
`response to the concerns raised by the
`new information on cyclamates, then-
`President Nixon directed FDA to
`reexamine the safety of GRAS
`substances (Ref. 3), and FDA announced
`that the agency was conducting a
`comprehensive study of substances
`presumed to be GRAS (35 FR 18623,
`December 8, 1970). The purpose of the
`study was to evaluate, by contemporary
`standards, the available safety
`information regarding substances
`presumed to be GRAS and to issue each
`item in a new (i.e., affirmed) GRAS list,
`a food additive regulation, or an interim
`food additive regulation pending
`completion of additional studies.
`4. GRAS Criteria and the GRAS
`Affirmation Process
`In the notice announcing the
`comprehensive agency review of
`presumed GRAS substances, FDA
`proposed criteria that could be used to
`establish whether these substances
`should be listed as GRAS, become the
`subject of a food additive regulation, or
`be listed in an interim food additive
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`regulation pending completion of
`additional studies (35 FR 18623). These
`criteria were incorporated into the
`agency’s regulations as § 121.3
`(precursor of current § 170.30 (21 CFR
`170.30)) (36 FR 12093, June 25, 1971).
`FDA made a second announcement
`that it was conducting a study of
`presumed GRAS substances (36 FR
`20546, October 23, 1971) and
`subsequently instituted a rulemaking to
`establish procedures that the agency
`could use, on its own initiative, to
`affirm the GRAS status of substances
`that were the subject of that review and
`were found to satisfy the criteria
`established in § 121.3 (proposed rule, 37
`FR 6207, March 25, 1972; final rule, 37
`FR 25705, December 2, 1972). These
`procedures were subsequently codified
`at § 170.35 (a) and (b) (21 CFR 170.35 (a)
`and (b)). Because the GRAS review did
`not cover all GRAS substances (e.g., it
`did not cover many substances that
`were marketed based on a
`manufacturer’s independent GRAS
`determination), that rulemaking
`included a mechanism (the current
`GRAS petition process; § 170.35(c))
`whereby an individual could petition
`FDA to review the GRAS status of
`substances not being considered as part
`of the agency’s GRAS review.
`In 1974, the agency proposed to
`clarify the criteria for GRAS status, the
`differences between GRAS status and
`food additive status, and the procedures
`being used to conduct the current
`review of food substances (39 FR 34194,
`September 23, 1974). The final
`regulations based on this proposal
`amended § 121.3 (current § 170.30) to
`distinguish a determination of GRAS
`status through scientific procedures
`(scientific procedures GRAS
`determination; current § 170.30(b)) from
`a determination of GRAS status through
`experience based on common use in
`food (common use GRAS determination;
`current § 170.30(c)) (41 FR 53600,
`December 7, 1976). Those final
`regulations also established definitions
`for ‘‘common use in food’’ (current
`§ 170.3(f)) and ‘‘scientific procedures’’
`(current § 170.3(h)). FDA subsequently
`added criteria (§ 170.30(c)(2)) for the
`determination of GRAS status through
`experience based on common use in
`food when that use occurred exclusively
`or primarily outside of the United States
`(53 FR 16544, May 10, 1988).
`5. The Plant Policy Statement
`FDA’s ‘‘Statement of Policy: Foods
`Derived From New Plant Varieties’’ (the
`plant policy statement) (57 FR 22984,
`May 29, 1992) is an example of a recent
`agency policy announcement regarding
`agency priorities in reviewing the GRAS
`
`status of substances added to food. In
`the plant policy statement, FDA
`reviewed its position on the
`applicability of the food additive
`definition and section 409 of the act to
`foods derived from new plant varieties
`in light of the intended changes in the
`composition of foods that might result
`from the newer techniques of genetic
`modification such as recombinant
`deoxyribonucleic acid (rDNA)
`techniques:
`The statutory definition of ‘‘food additive’’
`makes clear that it is the intended or
`expected introduction of a substance into
`food that makes the substance potentially
`subject to food additive regulation. Thus, in
`the case of foods derived from new plant
`varieties, it is the transferred genetic material
`and the intended expression product or
`products that could be subject to food
`additive regulation, if such material or
`expression products are not GRAS.
`(57 FR 22984 at 22990)
`In the plant policy statement, FDA
`provided extensive guidance, including
`criteria and analytical steps that
`producers could follow, on situations in
`which producers should consult with
`FDA to determine whether an FAP is
`appropriate. FDA also stated its intent to
`use its food additive authority in
`regulating foods and their byproducts
`derived from new plant varieties to the
`extent necessary to protect public
`health.
`C. Elements of the GRAS Standard
`Under section 201(s) of the act, a
`substance is exempt from the definition
`of food additive and thus, from
`premarket approval requirements, if its
`safety is generally recognized by
`qualified experts. Accordingly, a
`determination that a particular use of a
`substance is GRAS requires both
`technical evidence of safety and a basis
`to conclude that this technical evidence
`of safety is generally known and
`accepted. In contrast, a determination
`that a food additive is safe requires only
`technical evidence of safety.1 Thus, a
`GRAS substance is distinguished from a
`food additive on the basis of the
`common knowledge about the safety of
`the substance for its intended use rather
`than on the basis of what the substance
`
`1 In issuing a food additive regulation, the agency
`considers technical evidence of safety but does not
`address the GRAS standard of general recognition.
`Thus, in most cases, the agency’s issuance of a food
`additive regulation means that FDA did not
`consider the possible GRAS status of that substance.
`In a few cases (e.g., 21 CFR 173.357, cellulose
`triacetate used as a fixing agent in the
`immobilization of lactase enzyme preparation),
`FDA concluded, in evaluating the GRAS status of
`a substance, that the safety of a use of a substance
`was not generally recognized and authorized its use
`as a food additive rather than affirm it as GRAS (59
`FR 36935, July 20, 1994).
`
`is or the types of data and information
`that are necessary to establish its safety.
`To emphasize this distinction between a
`GRAS substance and a food additive,
`and to simplify discussion about the
`standard for general recognition of
`safety, in this document, FDA uses the
`term ‘‘technical element’’ when
`discussing technical evidence of safety
`and ‘‘common knowledge element’’
`when discussing general knowledge and
`acceptance of safety.
`The technical element of the GRAS
`standard requires that information about
`the substance establish that the
`intended use of the substance is safe. As
`discussed in section I.A of this
`document, FDA has defined ‘‘safe’’
`(§ 170.3(i)) as a reasonable certainty in
`the minds of competent scientists that
`the substance is not harmful under its
`intended conditions of use. Current
`§ 170.30(b) provides that general
`recognition of safety through scientific
`procedures requires the same quantity
`and quality of scientific evidence as is
`required to obtain approval of the
`substance as a food additive. Similarly,
`current § 170.30(c)(1) provides that
`general recognition of safety through
`experience based on common use in
`food prior to January 1, 1958, may be
`determined without the quantity or
`quality of scientific procedures required
`for approval of a food additive
`regulation and must be based solely on
`food use of the substance prior to that
`date. Current § 170.3(f) defines
`‘‘common use in food’’ as a substantial
`history of consumption for food use by
`a significant number of consumers.
`The common knowledge element of
`the GRAS standard includes two facets:
`(1) The data and information relied on
`to establish the technical element must
`be generally available; and (2) there
`must be a basis to conclude that there
`is consensus among qualified experts
`about the safety of the substance for its
`intended use. Neither facet is, by itself,
`sufficient to satisfy the common
`knowledge element of the GRAS
`standard.
`The usual mechanism to establish that
`scientific information is generally
`available is to show that the information
`is published in a peer-reviewed
`scientific journal. However,
`mechanisms to establish the basis for
`concluding that there is expert
`consensus about the safety of a
`substance are more varied. In some
`cases, publication in a peer-reviewed
`scientific journal of data (such as
`toxicity studies) on a test substance has
`been used to establish expert consensus
`in addition to general availability. In
`other cases, such publication of data
`and information in the primary
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`scientific literature has been
`supplemented by: (1) Publication of data
`and information in the secondary
`scientific literature, such as scientific
`review articles, textbooks, and
`compendia; (2) documentation of the
`opinion of an ‘‘expert panel’’ that is
`specifically convened for this purpose;
`or (3) the opinion or recommendation of
`an authoritative body such as the
`National Academy of Sciences (NAS) or
`the Committee on Nutrition of the
`American Academy of Pediatrics (CON/
`AAP) on a broad or specific issue that
`is related to a GRAS determination.
`In this document, FDA is using the
`term ‘‘consensus’’ in discussing the
`common knowledge element of the
`GRAS standard. Such consensus does
`not require unanimity among qualified
`experts (5,906 boxes, supra, 745 F.2d at
`119 n. 22; United 4,680 Pails, supra, 725
`F.2d at 990; Coli-Trol 80, supra, 518
`F.2d at 746; Promise Toothpaste, supra,
`624 F.Supp. at 782). For example, FDA
`would evaluate a single published
`report questioning the safety of use of a
`substance in food in the context of all
`the publicly available and corroborative
`information rather than conclude that
`such a report automatically disqualifies
`the substance from satisfying the GRAS
`standard (Cf. Coli-Trol 80, supra, 518
`F.2d at 746).
`D. The GRAS Petition Process
`The rulemaking process in § 170.35(c)
`whereby manufacturers may petition
`FDA to affirm that a substance is GRAS
`under certain conditions of use was
`designed as a voluntary administrative
`process whose purpose was to provide
`a mechanism for official recognition of
`lawfully made GRAS determinations. To
`the extent that a person elected to
`submit a GRAS petition, the process
`could facilitate an awareness, by the
`agency as well as the domestic and
`international food industry, of
`independent GRAS determinations.
`However, GRAS affirmation involves
`the resource-intensive rulemaking
`process, including: (1) Publishing a
`filing notice in the Federal Register; (2)
`requesting comment on the petitioned
`request; (3) conducting a comprehensive
`review of the petition’s data and
`information and comments received to
`the filing notice to determine whether
`the evidence establishes that the
`petitioned use of the substance is GRAS;
`(4) drafting a detailed explanation of
`why the use is GRAS (as opposed to
`simply being safe); and (5) publishing
`that explanation in the Federal Register.
`FDA believes that, in practice, this
`resource-intensive process deters many
`persons from petitioning the agency to
`
`affirm their independent GRAS
`determinations.
`II. Scope of the Proposed Regulations
`Based on its experience applying the
`provisions of § 170.30, FDA is proposing
`to clarify when use of a substance is
`exempt from the act’s premarket
`approval requirements because such use
`is GRAS. In proposing these changes,
`FDA is: (1) Emphasizing that a GRAS
`substance is distinguished from a food
`additive by the common knowledge
`about the safety of the substance for its
`intended use rather than by what the
`substance is, or on the basis of the types
`of data and information that are
`necessary to establish its safety; (2)
`identifying the types of technical
`evidence of safety that could form the
`basis of a GRAS determination; and (3)
`clarifying the role of publication in
`satisfying the general recognition
`standard. For consistency with the
`proposed changes to § 170.30, FDA is
`also proposing to amend the definition
`in § 170.3(h) of ‘‘scientific procedures.’’
`In addition, in keeping with the
`Reinventing Food Regulations, FDA is
`proposing to replace the current GRAS
`affirmation petition process (§ 170.35(c))
`with a notification procedure (proposed
`§ 170.36) whereby any person may
`notify FDA of a determination that a
`particular use of a substance is GRAS.
`The submitted notice would include a
`‘‘GRAS exemption claim’’ that would
`provide specific information about a
`GRAS determination in a consistent
`format. This GRAS exemption claim
`would include a succinct description of
`the ‘‘notified substance’’ (i.e., the
`substance that is the subject of the
`notice), the applicable conditions of use,
`and the basis for the GRAS
`determination (i.e., through scientific
`procedures or through experience based
`on common use in food) and would be
`dated and signed by the notifier. The
`GRAS exemption claim also would
`include a statement that the information
`supporting the GRAS determination was
`available for FDA review and copying or
`would be sent to FDA upon request. In
`addition to the GRAS exemption claim,
`the notice would include detailed
`information about the identity and
`properties of the notified substance and
`a detailed discussion of the basis for the
`notifier’s GRAS determination.
`Under the proposed notification
`procedure, the agency intends to
`evaluate whether the notice provides a
`sufficient basis for a GRAS
`determination and whether information
`in the notice or otherwise available to
`FDA raises issues that lead the agency
`to question whether use of the substance
`is GRAS. Within 90 days of receipt of
`
`the notice, FDA would respond to the
`notifier in writing and could advise the
`notifier that the agency has identified a
`problem with the notice. Although
`information in a notice would be
`publicly available consistent with the
`Freedom of Information Act (FOIA),
`FDA would make readily accessible to
`the public the notice’s GRAS exemption
`claim, as well as the agency’s response
`to the notice. However, FDA does not
`intend to conduct its own detailed
`evaluation of the data that the notifier
`relies on to support a determination that
`a use of a substance is GRAS or to affirm
`that a substance is GRAS for its
`intended use.
`FDA has tentatively concluded that
`the proposed notification procedure has
`advantages over the current petition
`process because the resource-intensive
`rulemaking that is associated with a
`petition would be eliminated. This
`streamlining would allow FDA to
`redirect its resources to questions about
`GRAS status that are a priority with
`respect to public health protection. In
`addition, the proposed notice is simpler
`than a GRAS affirmation petition and
`therefore conceivably would provide an
`incentive for manufacturers to inform
`FDA of their GRAS determinations. This
`would result in increased agency
`awareness of the composition of the
`nation’s food supply and the cumulative
`dietary exposure to GRAS substances.
`FDA has also tentatively concluded that
`the public health would be better served
`if some resources that are currently
`directed to the GRAS petition process
`were redirected to the preparation of
`documents that would provide the
`industry with guidance on certain food
`safety issues for complex substances
`(e.g., macroingredients or biological
`polymers, such as proteins,
`carbohydrates, and fats and oils).
`Finally, the reduction in resources
`devoted to the evaluation of GRAS
`substances would allow FDA to shift
`resources to its statutorily mandated
`task of reviewing food and color
`additive petitions.
`In light of its experience in reviewing
`GRAS petitions, FDA believes that the
`substitution of the proposed notification
`procedure for the current GRAS petition
`process would not adversely affect the
`public health because the agency would
`be replacing one voluntary
`administrative process with a different
`voluntary administrative procedure that
`would utilize FDA’s resources more
`effectively and efficiently. Under both
`the current and the proposed
`procedures, a manufacturer may market
`a substance that the manufacturer
`determines is GRAS without informing
`the agency or, if the agency is so
`
`RIMFROST EXHIBIT 1051 page 0004
`
`

`

`18942
`
`Federal Register / Vol. 62, No. 74 / Thursday, April 17, 1997 / Proposed Rules
`
`informed, while the agency is reviewing
`that information. Thus, from a legal and
`regulatory perspective, this substitution
`is neutral.
`FDA is also proposing to remove
`§ 170.30(f), which expresses the
`agency’s intent to review the GRAS
`status of certain food substances,
`because § 170.30(f) is redundant with
`the provisions of § 170.35 (a) and (b)
`that the agency may, on its own
`initiative, affirm the GRAS status of
`substances that directly or indirectly
`become components of food
`(§ 170.35(a)) or publish a notice
`announcing its conclusion that there is
`a lack of convincing evidence that the
`substance is GRAS and that it should be
`considered a food additive (§ 170.35(b)).
`FDA’s regulations regarding the
`eligibility of substances used in animal
`food or feeds for classification as GRAS,
`and the procedures for affirmation of
`GRAS status for such substances, are
`codified at §§ 570.30 and 570.35 (21
`CFR 570.30 and 570.35), respectively.
`FDA is proposing the following: (1) To
`amend the provisions of § 570.30 that
`are parallel to the provisions of current
`§ 170.30 (i.e., § 570.30 (a) and (b)); (2) to
`eliminate the GRAS affirmation petition
`process provided for in § 570.35 (a) and
`(c); and (3) to provide the option of a
`GRAS notification procedure for animal
`food or feeds that would be parallel to
`proposed § 170.36. FDA is proposing
`these changes because the regulations in
`part 570 (21 CFR part 570) implement
`the same statutory provisions as the
`regulations in part 170 (21 CFR part
`170).
`Finally, FDA is proposing to make
`certain conforming amendments to
`§§ 170.38, 184.1, 186.1, and 570.38.
`As FDA gains experience with the
`questions raised by industry in
`preparing notices, FDA expects, from
`time to time, to prepare guidance
`documents on issues of particular
`interest. However, such guidance
`documents are not a subject of this
`proposal.
`III. Proposed Revisions to § 170.30—
`Eligibility for Classification as GRAS
`A. General Criteria
`FDA is proposing to expand the
`description of the general criteria
`provided in current § 170.30(a) for a
`GRAS determination. FDA is not
`proposing any changes to the first two
`sentences of current § 170.30(a), which
`reflect the language of the GRAS
`exemption as set out in section 201(s) of
`the act.
`The final sentence of current
`§ 170.30(a) provides that general
`recognition of safety requires that there
`
`be common knowledge about the
`substance throughout the scientific
`community knowledgeable about the
`safety of substances directly or
`indirectly added to food. FDA is
`proposing to amend this provision to
`define what that common knowledge is
`(i.e., that there is reasonable certainty
`that the substance is not harmful under
`the intended conditions of use). In other
`words, proposed § 170.30(a) would
`clarify that the safety standard for a
`GRAS substance is identical to the
`safety standard in § 170.3(i) and that a
`GRAS substance is neither more safe nor
`less safe than an approved food
`additive. Rather, the distinction
`between a GRAS substance and an
`approved food additive is that, for a
`GRAS substance, there is common
`knowledge of safety within the expert
`community.
`B. Scientific Procedures