Opinion ID: 458862
Heading Depth: 2
Heading Rank: 1

Heading: Approval for Dry Use

Text: 4 In March 1973, Searle filed a petition with the FDA for the approval of aspartame for use in certain dry foods such as powdered beverages, desserts and dessert toppings, and chewing gum as well as for use as a tabletop sweetener (dry use). 38 Fed.Reg. 5921 (Mar. 5, 1973). In July 1974, aspartame was approved for the requested dry uses, provided that two warning notices appear on products containing aspartame. 39 Fed.Reg. 27317 (July 26, 1974). The first warning is: Phenylketonurics: Contains Phenylalanine. 21 C.F.R. Sec. 172.804(e)(2). This warning is necessary because a high plasma level of phenylalanine is associated with mental retardation in a small number of individuals with a genetic disorder that results in a lessened ability to metabolize phenylalanine. The second required statement cautions that aspartame for table use is not to be used in cooking or baking. 21 C.F.R. Sec. 172.804(e)(3). 5 Two parties lodged objections to aspartame's dry use with the FDA. Dr. John Olney (Olney) contended that the aspartic acid moiety of aspartame could cause brain lesions and neuroendocrine disorders in animals; therefore, according to Olney, aspartame posed a risk to human infants and children. 46 Fed.Reg. at 38285. James F. Turner, Esq. (Turner), who is counsel for petitioners in the instant cases, contended that phenylalanine moiety might lead to mental retardation. Id. Neither Olney nor Turner (collectively, the objectors) are parties to the instant proceeding. The FDA granted the objectors' request for a hearing. Subsequently, the objectors and the FDA agreed to substitute a three member Public Board of Inquiry (the Board) for the traditional hearing conducted by an Administrative Law Judge, as permitted by FDA regulations. See 21 C.F.R. Part 13. The Board was chosen by the FDA from a list of nominees submitted by the objectors. 46 Fed.Reg. 38286. 6 Before the hearing was convened, the FDA received reports that raised serious questions about the safety of aspartame and the methods by which it had been tested. In 1974, Searle submitted to the FDA a report of a study in which rats fed a principal degradation product of aspartame, called diketopiperazine (DKP), developed uterine polyps. Four teams of pathologists, including an FDA team, investigated the results to determine if the polyps revealed a safety hazard in connection with the consumption of aspartame. In addition, an FDA inspector filed reports that were critical of Searle lab practices, raising doubts as to the authenticity of Searle's reported data. An investigative task force appointed by the FDA found extensive problems with the quality and reliability of Searle's research practices and test results relating to aspartame as well as to seven other products. The task force reported that the Searle research practices were so severely flawed that the test results were unreliable. As a result, in December 1975, the FDA stayed its approval of aspartame for dry use, see 40 Fed.Reg. 56907 (Dec. 5, 1975), and delayed convening the Board until Searle's aspartame safety studies could be audited. 7 Following the stay, fifteen of the Searle studies were selected for an audit as to authenticity, i.e., that the tests and their results were neither faked nor misrepresented. The audit did not address the planning or execution of the studies or the correctness and meaning of the conclusions to be drawn from the studies. Twelve studies were audited by Universities Associated for Research and Education in Pathology (UAREP), a non-profit consortium of university pathologists. 46 Fed.Reg. at 38286. UAREP's inquiry was limited to the question of whether the experiments were carried out according to protocol plans and the accuracy and reliability with which the experiments were performed and reported to FDA. Id. at 38302. The FDA reviewed the remaining three studies and found them to be authentic. In addition, the FDA examined UAREP's report and found that the test results described were authentic. 8 The Board was convened in January 1980. During three days of public hearings, the Board considered the following questions: 9 1. [W]hether the ingestion of aspartame, either alone or together with glutamate, poses a risk of contributing to mental retardation, brain damage, or undesirable effects on neuroendocrine regulatory systems[.] 10 2. [W]hether the ingestion of aspartame may induce brain neoplasms (tumors) in the rat[.] 11 3. Based on answers to the above questions, 12 (a) Should aspartame be allowed for use in foods, or, instead should approval of aspartame be withdrawn? 13 (b) If aspartame is allowed for use in foods, i.e., if its approval is not withdrawn, what conditions of use and labeling and label statements should be required, if any? 14 44 Fed.Reg. at 31717. At the close of the hearings, the Board recommended that approval of aspartame be withdrawn until further study to establish whether or not a relationship existed between the ingestion of aspartame and brain tumors. As a result of this recommendation, the Board did not respond to the labeling question. The Board did agree with the FDA's determination that aspartame posed no risk of causing brain damage or endocrine dysfunction in people who used it. 46 Fed.Reg. 38288-89. 15 All parties to the Board's proceedings filed exceptions to its decision pursuant to 21 C.F.R. Sec. 12.125. On July 24, 1981, the FDA issued a final decision, concurring with the Board's finding that aspartame would cause no brain damage or endocrine dysfunction, but overruling the Board's conclusion regarding brain tumors. Consequently, the FDA's decision reinstated approval of aspartame for dry use. 46 Fed.Reg. 38285. None of the parties to the proceeding appealed the FDA's decision to the Court of Appeals.