Claire L. Kruger, Nancy Booth

A. Wallace Hayes

The use of the Generally Recognized as Safe (GRAS) process has been called into question because GRAS does not include premarket approval by the U.S. Food and Drug Administration (FDA). It may appear, on cursory inspection, that there are important differences underlying the frameworks for safety evaluation of food ingredients when comparing the GRAS process in the United States with the processes carried out in Europe by the European Food Safety Authority (EFSA) or globally by the Joint Expert Committee on Food Additives (JECFA). A more thorough examination, however, reveals the fundamental and crucial similarity of using Expert Scientific Panels to conduct risk assessments. In all instances, the independent experts for all of these panels must have the appropriate qualifications to carry out safety evaluations, and may come from varying backgrounds. A notable difference, however, is the issue of transparency, which can differentiate the GRAS process from the processes used by EFSA or JECFA. The transparency of the GRAS process is inherently greater than the transparency of the process used by EFSA and JECFA because of the public availability of the key data utilized in the GRAS review. For pivotal scientific information, a GRAS Panel must rely only on published studies—in other words, information that is subject to scrutiny by any interested party. In contrast, EFSA and JECFA experts often rely on confidential results from studies contracted or carried out by industry. This can create an appearance of a potential conflict of interest and/or bias, especially when scientific experts from industry are readily allowed to apply for membership on various panels and committees that serve EFSA (Corporate Europe Observatory, 2011).

In the U.S., many ingredients are marketed for use on the basis of a GRAS exemption to the food additive definition. In this way, the use of a GRAS ingredient is not subject to premarket review and approval by FDA. Because self-determining the GRAS status of an ingredient does not depend upon FDA premarket approval,the speed and efficiency of this process is a strong benefit. The GRAS process, when carried out with due diligence, is a robust, comprehensive, and transparent safety evaluation process. At its essence, GRAS is a scientific peer-review process that is based on widespread knowledge among a community of qualified experts and relies on publicly available scientific evidence to support reasonable certainty in the minds of these competent scientists that the substance is not harmful under its intended conditions of use.

Experts who serve on GRAS Panels in the U.S. are expected to be individuals who are qualified by scientific training and experience to evaluate the safety of food substances (Federal Register, 1997). However, the FDA has not officially opined on a definition of “expert,” leaving it to companies to identify and recruit appropriate scientific experts to serve on GRAS Panels. Nor has the FDA issued guidance regarding the definition of conflicts of interest for those who serve on Expert Panels convened by companies to self-determine the GRAS status of an ingredient. Therefore, the FDA cannot evaluate whether the determinations of such Expert Panels are arrived at without bias. However, there is a robustness and transparency inherent in the process itself because a GRAS determination relies on common knowledge about the safety of the substance for its intended use. Additionally, the consensus regarding the acceptance of the safety of a substance for its intended use occurs among qualified experts who document the basis for their conclusion in written form. Thus, a GRAS determination is based on the general availability of the data and information on the substance under evaluation. GRAS determinations that are voluntarily notified to FDA are posted on its website.

--- PAGE BREAK ---

In the European Union (EU), EFSA is the risk assessment agency for food and feed safety. EFSA generally provides advice, as opposed to making regulatory decisions; however, the influence of this body is reflected in policy decisions. Scientific experts from EU member states are recruited to sit on EFSA Scientific Panels, and those who serve in this capacity should demonstrate experience in carrying out scientific risk assessments and be qualified experts in a relevant field. A large part of EFSA’s work is undertaken in response to specific requests from the European Commission, the European Parliament, and EU Member States. EFSA has established key operating principles and rules including a commitment to openness and transparency. In addition, EFSA is bound by EU legislation on issues such as public access to documents, and EFSA publishes the outcomes of its scientific work on its website. However, the transparency of the process by which the panels produce their recommendations can and probably should be broadened. The public is not well-informed about how opinions are developed, which data are used to arrive at an opinion, and how these data are selected for inclusion in the decision-making process, and this has detracted from what should be a truly transparent process. The timeliness for delivery of an opinion is seen as the biggest challenge (FPA Market and Management Advice, 2010). While EFSA is not overtly political, its stance on certain issues suggests an accommodation to sensitivities (e.g., genetically modified organisms and products derived from them). EFSA has been the target of increasing criticism regarding its independence from industry and alleged conflicts of interest for committee members.

JECFA is an international expert scientific committee administered jointly by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO). JECFA performs a vital role in providing a reliable and independent source of expert advice in the international setting, thus contributing to the setting of health-protective food-related standards on a global scale. JECFA is not a regulatory body per se; however, it is well-known that many countries use published opinions from JECFA as the basis of their national regulations for food additives. For example, the Codex Committee on Food Additives and Contaminants and the Codex Committee on Residues of Veterinary Drugs in Food both develop standards based on evaluations by JECFA. The detailed conclusions of JECFA meetings are published in the WHO Technical Report Series at

FAO and WHO have complementary functions in selecting experts to serve on JECFA by establishing a list of appointed experts in areas of interest to each of the two organizations. Committee or meeting member selection is carried out with consideration of the scientific credentials of candidates having scientific expertise in the needed emphasis areas (JECFA, 2009). However, similar conflict of interest issues have been highlighted for JECFA-appointed scientific experts, along with the reliance on the use of unpublished data when carrying out safety assessments. Additional procedural transparency could increase confidence in this process. JECFA publishes summaries of the data that are used in risk assessments, including literature citations, in the WHO Food Additive Series, which includes toxicological and intake monographs on food additives; these are available from INCHEM at

--- PAGE BREAK ---

Appropriate guidance on what constitutes conflict of interest should be provided to members of all Expert Panels used to evaluate the safety of new food ingredients to provide assurance that evaluations will be carried out in a manner that will maintain public confidence. In addition, transparency is critical to maintain public confidence in the food safety evaluation process. The public nature of the GRAS determination, relying on published data as the source of the pivotal information, makes the GRAS process the most transparent and, therefore, potentially the most robust and powerful tool currently used worldwide for evaluating new food ingredients. The GRAS mechanism, or a close variant, could readily be adapted for use in other countries. One criticism that can be lodged against GRAS is that the FDA is less informed about the nation’s food supply than it could be because Notification of GRAS determinations to the FDA is not mandatory (GAO, 2010). One approach to further strengthen the GRAS process would be for the FDA to seek authority from Congress to require all companies to Notify the FDA of their GRAS determinations. Although it would place a greater burden on FDA, requiring Notification would further enhance transparency of the GRAS process by allowing easier public scrutiny of the scientific information compiled in support of an ingredient’s safety. Even without FDA Notification, GRAS is an efficient, robust, transparent, and successful process for evaluating the safety of food ingredients.References cited in this column are available from the authors.


Claire L. Kruger, Ph.D., Contributing Editor • CEO, COO, and Director of Health Sciences, Spherix Inc., Bethesda, Md. • [email protected]

Nancy Booth, Ph.D., Contributing Editor • Senior Science Consultant, Spherix Inc., Bethesda, Md. • [email protected] 

A. Wallace Hayes, Ph.D., Contributing Editor • Visiting  Scientist, Harvard School of Public Health, Cambridge, Mass. • [email protected]