CENTER FOR FOOD SAFETY AND APPLIED NUTRITION (CFSAN)
Calgene was the first company to approach FDA about the regulatory status of its Flavr Savr™ tomato altered using R-DNA techniques to reduce the rate of ripening. It submitted two requests for advisory opinions inquiring about the status of the use of the kanamycin-resistance marker and about the status of the altered tomato product itself. Ultimately, the use of the marker resulted in a food additive regulation for human and non-human animal, so-called “feed,” uses. See 21 CFR §§ 173.170, 573.130. This is the only food additive regulation to be issued covering any R-DNA-derived food ingredient.
In 1992, FDA published its policy on human and other animal foods derived from new plant varieties, which is still operative today. See HHS, FDA, Statement of Policy: Foods Derived From New Plant Varieties, Notice, 57 Fed. Reg. 22984 (1992). This policy essentially establishes a voluntary consultation process for “bioengineered” plants. A list of bioengineered plants that have successfully completed the consultation process appears at www.cfsan.fda.gov/~lrd/biocon.html. The 1992 Policy Statement was unsuccessfully challenged in court in Alliance for Bio-Integrity v. Shalala, 115 F.2d 166 (D.D.C. 2000). Voluntary consultation procedures also do not involve NEPA considerations, whereas food additive petitions do. The first food ingredient affirmed as generally recognized as safe (GRAS) in 1990 by FDA developed through the use of recombinant DNA is chymosin obtained from genetically modified E. coli K-12. See 21 CFR § 184.1685(a)(2).
A number of human food ingredients have been the subject of GRAS notifications, including asparaginase enzyme preparation from Aspergillus oryzae expressing the asparaginase gene from A. oryzae; lipase preparation from Aspergillus niger expressing a gene encoding a lipase from Candida antartica; phospholipase enzyme preparation from Aspergillus oryzae expressing the gene encoding a phospholipase A1 from Fusarium venenatum; and alpha-amylase enzyme preparation from Pseudomonas fluorescens Biovar I expressing a gene encoding a hybrid alpha-amylase derived from three microorganisms within the order Thermococcales.
In 2001 FDA issued a proposed rule that, if it had been finalized, would have required food developers to notify the agency at least 120 days in advance of their intent to market human or other animal “bioengineered food,” among other ingredients. This initiative was largely taken in response to the Clinton Administration’s efforts to strengthen science-based regulation and consumer access to information. See HHS, FDA, Premarket Notice Concerning Bioengineered Foods, Proposed Rule, 66 Fed. Reg. 4706 (2001). It was never acted upon largely because of the change in Administrations.
Perhaps no subject area has been as controversial as FDA’s stance of not requiring special labeling for “biotech” foods, a topic that has been the subject of several Federal Register notices. See, e.g., 57 Fed. Reg. at 22991 (1992); HHS, FDA, Food Labeling; Foods Derived From New Plant Varieties, Request for Data and Information, Request for Data and Information, 58 Fed. Reg. 25837 (1993).
The agency has stated that it is not aware of “any information showing that foods derived from [the new methods] differ from other foods in a meaningful or uniform way, or that, as a class, those developed by the new techniques present any different or greater safety concern than foods that are developed by traditional plant breeding.” 57 Fed. Reg. at 22991 (1992). It has noted, however, that special labeling regarding the use of recombinant DNA technology may be required in certain instances, such as where the food differs significantly from its conventional counterpart to the extent that the common or usual name may no longer apply or if the food contains a new protein that commonly causes allergic reactions.
The agency has repeatedly been urged to change its position on labeling as a result of international pressures and U.S. groups who argue that consumers have a right to know what they are eating, among other reasons. FDA has developed a draft guideline on labeling, entitled Draft Guidance for Industry: Voluntary Labeling Indicated Whether Foods Have or Have Not Been Developed Using Bioengineering; Availability; HHS, FDA, Notice, 56 Fed. Reg. 4839 (2000). The court in Alliance for Bio-Integrity, mentioned previously, held that the special labeling for genetically engineered foods as a class is not required solely because of consumer demand.
Questions about the adequacy of U.S. regulation of bioengineered food peaked in 2000 with the discovery of the widespread presence of StarLink® corn in human food. The trait involving Cry9C protein from the bacterium Bacillus thuringiensis (Bt) in StarLink® corn had been registered as a pesticide by EPA for animal feed and other industrial non-human food uses. It accidentally ended up in the human food supply, both domestically and internationally, causing a class action lawsuit, significant economic loses, and international regulatory turmoil. Both EPA and FDA have recently proposed to stop requiring continued testing for Cry9C. See, e.g., HHS, FDA, Guidance for Industry on FDA Recommendations for Sampling and Testing Yellow Corn and Dry-Milled Yellow Corn Shipments Intended for Human Food Use for Cry9C Protein Residues; Comments on Possible Withdrawal, Notice, 72 Fed. Reg. 58980 (2007).
Perhaps most significantly, the StarLink® corn episode brought increased awareness of the possibility of the accidental or adventitious presence (AP) of low levels of bioengineered plant traits appearing in conventional or organic food crops and in commodity grain in trade channels. This could occur through plant cross-pollination, intermingling or commingling with other commodities, and by other means. Thus, compatibility and co-existence issues have been raised with conventional and organic agriculture. The topic of “zero tolerances” or “zero allowances” for AP continues to dominate domestic and international regulatory and trade debates.
The AP debate became intensified after the StarLink® corn incident with the discovery that another Bt pesticidal trait found in Bt 10 corn was present in human and other animal food. This Cry1Ab trait in Bt 10 corn was not approved for any uses. Nevertheless, it was very similar or closely related to that in Bt 11 corn, a bioengineered corn line also containing Cry1Ab that had undergone complete U.S. regulatory clearances. Hence, particularly given its low levels, FDA (and EPA) decided there were no food safety or environmental concerns. See, e.g., U.S. Food and Drug Administration Statement on Bt 10 at http://www.cfsan.fda.gov/~lrd/biobt10.html (April 27, 2005).
A similar conclusion was also recently drawn regarding trace amounts of bioengineered rice that were detected in commercial rice seed. The bioengineered variety of rice called LLRICE601 and LLRICE604 express tolerance to a particular herbicide, which was found in non-engineered rice lines. Since the protein that provides herbicide tolerance was previously evaluated by FDA, the agency concluded that the presence of this trait in human and other animal food did not present a safety concern. See U.S. Food and Drug Administration’s Statement on LLRICE600 Series (March 23, 2007) at http://www.cfsan.fda.gov/~lrd/biorice2.html.
Not surprisingly, the topic of the bioengineering of plants to produce pharmaceuticals has been especially controversial in light of StarLink® and other AP controversies. Moreover, the finding in 2002 that approximately one half a million bushels of soybeans intended for human use contained drug-producing corn has produced additional debate about environmental aspects of field testing of pharma plants. FDA Talk Paper, FDA Action on Corn Bioengineered to Produce Pharmaceutical Material T02-46 (Nov. 19, 2002) at www.fda.gov/bbs/topics/ANSWERS/2002/ANS01174.html. Accordingly, both FDA and USDA have developed a guidance on such plants pertaining to confinement and other product development considerations. See, e.g., Drugs, Biologics, and Medical Devices Derived From Bioengineered Plants for Use in Humans and Animals (Sept. 2002), available at www.fda.gov/cber/gdlns/bioplant.htm.
The topic of AP has also led the various agencies to issue policy approaches or statements, which also have been controversial. See, e.g., HHS, FDA, Guidance for Industry; Recommendations for the Early Food Safety Evaluation of New Non-Pesticidal Proteins Produced by New Plant Varieties Intended for Food Use, Availability; Notice, 71 Fed. Reg. 35688 (2006).
