In the midst of the dog days of summer and just before a looming court imposed deadline, the U.S. FDA issued a long-awaited rule finalizing the regulations governing the Agency’s voluntary “generally recognized as safe” (GRAS) Notification program. FDA’s GRAS Notification program has been a successful, albeit somewhat controversial, process by which new food ingredients and new uses of food ingredients can be sanctioned (by FDA) for use in food. Since the program’s inception in 1997, the safety of hundreds of new ingredients have been reviewed by FDA under the proposed program.
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The final rule brings to an end a regulatory process that began in 1997, when FDA published its first proposed rule on GRAS substances. By 1998, FDA was accepting GRAS notifications from industry. While the final rule is largely similar to what FDA proposed in 1997, it does include a number of important updates, and also details the new format requirements for GRAS notices submitted to FDA.
The GRAS Notification process has been positively viewed by the food industry as a more efficient means of establishing a suitable regulatory status for substances used in food. One of the main benefits to industry and FDA is that the Notification process avoids the resource intensive food additive petition rulemaking process, under which it often took FDA four years or longer to clear a new food ingredient. In contrast, FDA is usually able to make a conclusion on a GRAS Notification for an ingredient in about six months. The data requirements necessary for the Notification and requisite safety standard, however, are the same for an ingredient reviewed by either procedure.
A GRAS determination is somewhat different from a legal standpoint than the premarket clearance of a food ingredient. In 1958, when Congress passed the Food Additives Amendment Act, it carved out an exemption from the definition of “food additive” for substances that are “generally recognized, among experts qualified by scientific training and experience to evaluate [their] safety, as having been adequately shown through scientific procedures (or, in the case of a substance used in food prior to Jan. 1, 1958, through either scientific procedures or experience based on common use in food) to be safe under the conditions of its intended use.” Substances that are determined to be GRAS are exempt from FDA’s premarket clearance requirements for food additives. Substances that are not GRAS must be the subject of a food additive regulation, which requires a rulemaking process. Manufacturers do not have to obtain FDA’s review of a substance that is properly determined to be GRAS. In some cases, manufacturers may feel comfortable making their own determination, without FDA’s review, that a substance is GRAS under its intended conditions of use. Although manufacturers are legally entitled to make these determinations, market pressures often compel companies to obtain FDA’s concurrence on the GRAS status of a substance.
What’s in Final Rule?
As noted above, the final rule is largely similar to what FDA previously proposed. FDA first published rules governing the voluntary Notification program when the program was proposed in 1997. It subsequently republished the proposal with some changes in 2010 and reopened the comment period. Importantly, the final rule includes a detailed discussion of the use of data to support a “GRAS conclusion.” Specifically, FDA states that a GRAS conclusion must be based on data that are generally available and accepted, and as such, are publicly available. The rule notes that the usual mechanism to establish that scientific information is generally available to the expert scientific community is publication in a peer-reviewed journal. Notably, the final rule provides that unpublished data can corroborate a GRAS conclusion, and should not be ignored, but cannot form the basis of a GRAS conclusion.
The final rule also details new formatting requirements for GRAS notifications, which should be arranged into the following seven parts: 1) Signed statements and certification; 2) Identity, method of manufacture, specifications, and physical or technical effect; 3) Dietary exposure; 4) Self-limiting levels of use; 5) Experience based on common use in food before 1958, if applicable; 6) Narrative; and 7) List of supporting data and information. All seven parts must be included.
Some of the other notable changes include the following.
- New provisions are included on the submission and treatment of trade secret and confidential information in the GRAS Notice. (The proposed rule assumed that GRAS Notices would not contain any information protected under the Freedom of Information Act. The final rule permits some limited submission of trade secret and confidential information. However, if trade secret or confidential information is included, the notifier must establish how GRAS status can be supported without the trade secret or confidential information having a bearing on the safety determination.)
- FDA will review a GRAS notice within 180 days, with a possible 90-day extension. Up to now the program has been operating without an FDA review time frame.
- A requirement that a GRAS Notice discuss information that is or appears to be inconsistent with the notifier’s conclusion of GRAS status or certification that the notifier is not aware of such information.
- A requirement that a notification include some discussion of technical effect when such information has bearing on the safety evaluation.
- Between 1972 and the proposal of the voluntary GRAS Notification rule in 1997, FDA had in place a voluntary GRAS affirmation petition process. Under that process, companies could petition FDA to review the GRAS status of a substance and, if FDA agreed with the GRAS conclusion, it would issue a food additive regulation affirming that the substance was GRAS. Although the affirmation process was effectively abandoned in 1998 with the advent of the GRAS notification pilot program, FDA never formally ended the process. Thus, the final rule brings the GRAS affirmation petition process to an official end.
The fact that the 1997 proposed GRAS Notification rule was never finalized was criticized both by the Governmental Accountability Office (GAO) and a number of public interest groups. In addition, public interest groups have long argued against the GRAS exemption from the rulemaking process because it permits companies to make a self-determination on the safety of a food ingredient. It was the hope of several of these groups that FDA would severely curtail the use of GRAS self-determinations by industry and require even further scientific data than was proposed in the previous proposal for the GRAS Notification rule. FDA concluded that it did not have the legal standing to eliminate self-determinations and it further decided that its requirements as set forth in the proposed rules was protective of the public health.
In summary, FDA’s final rule on GRAS substances does not represent a significant change in the way that the GRAS notification program operates or a company’s own determination on whether a substance is GRAS. The final rule, however, does provide some needed clarity for industry with respect to how FDA believes GRAS conclusions should be made. For many companies, the GRAS exemption is an important statutory mechanism to establish a suitable legal status for a product, and therefore, the final rule has importance to their businesses.
Hill, a partner with Keller and Heckman LLP, served as chair of the GMA/NSF Joint Committee on Generally Recognized as Safe Publicly Available Standard. Reach him at firstname.lastname@example.org. Dages, an associate at Keller and Heckman, practices in the area of food and drug law and advises clients on product compliance issues involving the FDA. Reach him at email@example.com.