The regulation and innovation responsible for the approximate 70% reduction in food spending since 1950[1] has come under fire with some regularity in recent years. The basis for the arguments against the current regulation focus on the perceived risk in food safety as a result of food additives and ingredients, the mitigation of which would be accomplished by sifting through a large body of evidence demonstrating generally recognized safety, and mandating testing on the basis of what amounts to a checklist of today’s science[2], leaving no room for the science of the future. This endeavor is not only unnecessary[3], but would increase the cost of the foods in question by exacting drug-program-like fees from food companies[2] or delay or prevent foods from entering the consumer market by creating timelines comparable to those for drugs. At the foundation of today’s affordable and abundant American food market is a system applying the sound principles of science in order to fulfill regulation. The evolution of the science of that system fosters compliant innovation within the food industry, making food bigger, better, cheaper and food production faster and less costly. Reform of the regulation of the system would net diminishing returns, with an end state very similar to today in safety, but with great sacrifices in food selection, affordability, and convenience as a result of the increased pre-market costs to a food manufacturer. A review of the science and regulation supporting the general recognition of safety of food ingredients and the trends in compliant innovations, against this backdrop of the economic evolution of food, make clear the fact that the current system has evolved on its own to value science and question the status quo.
The rapid growth required for the post-World War II transformation of the food industry brought with it new regulatory challenges that mandated action for: 1) the safety of the public, 2) the continued innovation of the manufacturers, 3) the efficiency and effectiveness of regulatory oversight for the Food and Drug Administration (FDA). Thus, the 1958 Amendment to the Federal Food Drug and Cosmetic Act was written into law, creating a distinct class of substances that are generally recognized as safe (GRAS) in addition to the definition “food additive”[3]. The primary impact of this regulation with respect to food ingredient safety was the creation of a path for food ingredient approval that allowed manufacturers to deem a food ingredient safe in its intended use, without (or optionally with) the consultation of the FDA. GRAS “self-affirmation” is still attainable today, by either demonstrating a basis of safety through history of common use in food prior to January 1, 1958, or through scientific procedures[3].
In either approach, the basis of GRAS is dependent upon the intended use of the ingredient, which is often described in a company’s product specifications document or ingredient file, along with the physical and chemical characteristics of an ingredient, its origin, estimated daily intake, and the foods to which it is likely to be added. An often overlooked aspect of the GRAS process is the method by which an ingredient is manufactured, and to which quality and safety controls are added to ensure ingredient quality and safety (Figure 1). In execution, the requirements of any GRAS include demonstration of common knowledge about the substance within the scientific community, usually through peer-reviewed publication, and the convening of an expert panel to determine the substance GRAS[4]. As a result, every GRAS has a sound basis in science. The scientific core of GRAS is further emphasized when the rest of the GRAS process is examined. Reviewing the “scientific process” of a “scientific procedures” GRAS would be redundant in the purpose of this discussion, however, reviewing the process for a common use GRAS is surprisingly illustrative of the science involved.
Figure 1. Foundational scientific aspects of any GRAS determination
It seems almost instinctive to select the GRAS route of common use in food for a “natural” product. The benefit of a common use GRAS for industry is that it is often the fastest way to bring an ingredient to market with compliance. However, in application, GRAS by common use in food is both the most rarely used, and potentially the hardest path by which a food ingredient can become federally compliant.
For a common use GRAS, a food company must provide at least two independent pieces of information documenting common use, which also demonstrate that the specifications and (generally the same) process at the time of the GRAS match those pre-dating 1958[4]. This is often challenging, if not impossible, because the literature and documentation supporting manufacturing processes and food quality were lacking at and prior-to mid-century; a contributing factor to the question of food additive safety addressed in the 1958 Food Additive Amendment[3]. As if these requirements did not represent a high enough threshold, one aspect of the regulation notes that FDA “should” be consulted and concur with a determination of GRAS on the basis of common use with historical data from a country other than the United States. In fact, notifying FDA of any GRAS determination is entirely optional and while the use of the word “should’ in the regulation likely has some influence upon readers, it holds no enforceable weight. However, even though FDA’s contribution to GRAS has only ever been elective, their influence has been impactful—though, in the end, not always as intended. Until 1983, when FDA’s decision that information supporting common use in food had to be from the United States was overturned in an appeal regarding an imported jelly containing a seed that was widely used in China prior to January 1, 1958[5]. The decision from the appeals court was essentially that safe consumption of food was not an exclusive habit of U.S. citizens and therefore, evidence from other countries must be given equal consideration as historical support in a common use GRAS evaluation with equal opportunity and no discrimination by country[5].
Though the requirement for U.S.-only data was lifted by precedent in 1983[5] lending to an idea that new ingredients from outside the U.S. would be likely to gain approval for addition to food in the U.S. by means of a common use GRAS, leading to an increase in GRAS filings with FDA, the data demonstrate a trend to the contrary. In fact, it indicates an impending extinction of common use GRAS in the early 2000’s (Figure 2).
Figure 2. GRAS Ingredient Filing Trends with FDA (as of July 2015)[7][2][6]
Figure 2 was generated using data obtained from FDA websites and reports critical of industry. The values of ingredients included in Section 184 of the Code of Federal Regulations (CFR) were split on the basis of an estimation presented by FDA staff, that approximately 20% of the ingredients included in that section were included as a result of industry submitted GRAS Affirmations. Therefore, the net remaining ingredients in Section 184 were presumed to have originated on the basis of common use prior to review by the Select Committee on GRAS Substances (SCOGS)[6]. In reviewing a search of the current FDA GRAS Notification (GRN) database, less than 1% of those acknowledged with “No Questions” received replies describing a record filing by means of the common use method of GRAS[7]. All other historical use submissions were either found to have no basis or were re-submitted through scientific procedures and met with “No Questions”[7]. The three notifications (covering ten enzyme preparations) as food processing aids, and one notification (covering three herbal preparations) for herbal tea flavors which received favorable FDA responses, are the sole ingredients to have been acknowledged by FDA on the basis of common use in the last eighteen years (Table 1)[7].
Table 1. Common Use GRNs acknowledged by FDA with a “No Questions” letter as of July 15, 2015.
The steep decline in common use GRAS filings/findings warrants at least some speculation as to the origin of the trend. There are two likely explanations for its decline: (1) that most of the substances that could be supported by history of use have already been GRASed and/or were simply added to food with the presumption they were GRAS, or (2) that the substances were not GRASed on the basis of common use and subsequently notified because FDA might not have agreed with the basis of the GRAS (i.e., an “inadequate basis for GRAS”)[3]. The most likely explanation is that both of these forces have been at work in influencing common use GRAS filings to date, however, not in an expected way.
The majority of food additives and ingredients reviewed and approved for use in the 1950’s and 1960’s were approved for use in their natural state or in a state (e.g., extract, oil) that could be developed in a lab and transferred to large scale production with minimal effort or risk, approximating the pre-1958 product (based upon science of the time). Because the GRAS decision on safety is focused on the use of the ingredient, the limits of human imagination and technology at the time likely exhausted the available uses of any food in common use before 1958 within a decade or two of the Food Additive Amendment. As time passed, the further from 1958 a GRAS was reviewed, common use as an argument for safety became less and less possible because fewer and fewer cases could be made that a product and its use were equivalent to a pre-1958 version of that product and its use, given the cultural, industrial and technological shifts that happened in the 1980’s through 2010’s (Figure 3). As technology improved, influence over an ingredient’s properties improved. As a result, the efficiency of production improved and the ability to measure the ingredient in use improved as well. Another iteration of product improvements broke the product down into its pieces and parts. This cycle of improvements will no doubt continue into the future. While a majority of the raw materials in use today are basically the same food commodities present pre-1958, their processing, the final ingredients, and their intended use grow further and further from their point of embarkation more than a half-century ago[8]. This difference can no longer be reconciled without scientific procedures.
Figure 3. Patent Search Results Trends Pre-2000 through 2015[9].
The unexpected explanation for the extinction of common use GRAS lies not in the lack of foods available for GRAS determination—it lies in the seemingly arbitrary date from which the baseline for comparison of the food’s qualities and production must be drawn. But the date was not arbitrary, it was the point at which both safety and technology in food were identified critical to Americans. Whether intended or serendipitous, this assigned inflection point of January 1, 1958 actually did much to determine the adequacy of the data in a GRAS determination today. It created the foundation from which a robust food approval system evolved on its own producing more compliant food innovation than ever before in American history. Somewhere around 2002, the likelihood that data from the 1950’s or before would ever again be adequate for demonstration of safety approached zero. Through natural selection scientific procedures prevailed, and will continue to evolve. Mid-century technologies had a 50-year lifespan, and with their expiry at the turn of the century, common use GRAS died with them.
References
[1] Thompson, Derek. How American Spends Money: 100 Years in the Life of the Family Budget. The Atlantic Monthly. [Online] April 5, 2012. [Cited: SEP 29, 2015.] http://www.theatlantic.com/business/archive/2012/04/how-america-spends-money-100-years-in-the-life-of-the-family-budget/255475/.
[2] Navigating the U.S. Food Additive Regulatory Program. Neltner, Thomas G., et al. s.l. : Institute of Food Technologists, 2011, Comprehensive Reviews in Food Science and Food Safety, Vol. 10.
[3] Generally recognized as safe (GRAS): history and description. Burdock, George A. and Carabin, Ioana G. 1, s.l. : Elsevier Ireland, Ltd., Toxicology Letters, Vol. 150.
[4] 21 CFR 170.30 (a), (c)(2).
[5] Fmali Herb, Inc. v Heckler. 715 F.2d 1385, 1386, s.l. : Ninth Cir., 1983.
[6] U.S. Food and Drug Administration. FDA’s Approach to the GRAS Provision: A History of Processes. U.S. Food and Drug Admininstration Website. [Online] July 29, 2015. [Cited: September 30, 2015.] http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/ucm094040.htm.
[7] —. GRAS Notices. U.S. Food and Drug Administration Website. [Online] July 01, 2015. [Cited: September 13, 2015.] http://www.accessdata.fda.gov/scripts/fdcc/?set=GRASNotices.
[8] American Association of Cereal Chemists. Centennial Activities. AACC International Website. [Online] 2015. [Cited: September 30, 2015.] http://www.aaccnet.org/meetings/annual/overview/Pages/AACCICentennialActivities.aspx.
[9] Lexis Nexis. Keywords: “Food,” “Technology,” “Extraction”. Patent Search. 2015.