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

Heading: The Statutory Provision for a Hearing

Text: 34 Under such limited scope of review and a delineation of the issues upon which the review must be focused, we conclude that Appellants have failed to demonstrate that the FDA abused its discretion by denying a hearing. The FDA's decision to approve a food additive is governed by Section 409 of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. Sec. 348. Under this statute, a new food additive is to be approved if a fair evaluation of the data indicates the safety of the ingredient. Id. at Sec. 348(c)(3). FDA has interpreted safety to mean that there is a reasonable certainty in the minds of competent scientists that the substance is not harmful under the intended conditions of use. 21 C.F.R. Sec. 170.3(i). Appellants argue that the Act mandates a nondiscretionary grant of a hearing by the FDA upon the objection of an interested party. That is not what the statute says. A hearing is only available if petitioners raise a material issue in their objections. The statute provides that any person adversely affected by the approval or rejection of a food additive petition may within thirty days of the order file objections and request a hearing. 21 U.S.C. Sec. 348(f)(1). However, the statute requires that the objections specify with particularity the provisions of the order deemed objectionable and state reasonable grounds for the objections. The Secretary shall hold such hearing for the purpose of receiving evidence relevant and material to the issues raised by such objections. If the agency determines that no hearing is necessary, the regulation approving the food additive becomes final. 35 It is well established that the statutory grant of a public hearing is not absolute. A request for a hearing must contain evidence that raises a material issue of fact on which a meaningful hearing might be held. Pineapple Growers Ass'n v. FDA, 673 F.2d 1083, 1085 (9th Cir.1982). In addition, the issue of fact raised by the objecting party must go to the legality of the agency's order. Id. at 1085, quoting Dyestuffs and Chemicals v. Flemming, 271 F.2d 281, 286 (8th Cir.1959), cert. denied, 362 U.S. 911, 80 S.Ct. 681, 4 L.Ed.2d 619 (1960) (Where the objections stated and issues raised thereby are, even if true, legally insufficient, their effect is a nullity and no objections have been stated.) The FDA's own regulations reflect this requirement that a challenge to an agency's factual conclusion must present a live controversy and affect the legality of the agency's determination to act in a certain way. See Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S. 609, 620-22, 93 S.Ct. 2469, 2478-79, 37 L.Ed.2d 207 (1973). In 21 C.F.R. Sec. 12.24(b), the FDA requires that a person seeking to justify a hearing on objections to approval of a food additive must show 1) the existence of a genuine and substantial issue of fact to be resolved at a hearing; 2) that the factual issue can be resolved by available reliable evidence; 3) the objecting party's data and information, if proved, would be sufficient to resolve the factual issue in the way sought by the objecting party; and 4) resolution of the factual issue in that way would suffice to warrant the relief requested. If the objecting party fails to make these threshold showings, the FDA denies the hearing request. 36 B. The FDA's Examination of the Evidence of the Dangers of Aspartame for Wet Use 37 As pointed out above, Appellants may obtain a hearing on issues decided during the approval of aspartame for dry use only if they introduced new evidence suggesting that reliance on those issues in the context of wet use is erroneous. Appellants contend that they have introduced this new evidence on the questions of: 1) the relationship between the ingestion of aspartame and brain lesions, mental retardation, and mental instability; 2) the availability of new and more sophisticated tests for the formation of the toxic chemical nitrosamine as a result of aspartame ingestion; 3) the increase in average daily consumption of aspartame resulting from its use in carbonated beverages; 4) the carcinogenicity of aspartame; and 5) the labeling requirements for aspartame. Our review of each of these contentions leads us to conclude that Appellants have not introduced any new evidence suggesting that the FDA, in its approval of aspartame for wet use, abused its discretion in relying on tests and studies conducted previously in connection with the effects of consuming aspartame in dry uses. 38 1. Brain Damage. Appellants argue that there is a material issue of fact on whether the approval of aspartame for carbonated beverage use would increase the level of phenylalanine in blood plasma, which would in turn cause changes in the production of the brain's neurotransmitters. Petitioners then speculate that these changes might lead to aberrations in behavior. In support of this argument, Appellants cite letters from Dr. Richard Wurtman to the director of the Bureau of Foods at the FDA. Two effects concerned Dr. Wurtman. First, his data indicated that large doses of aspartame given to humans and rats after they had been deprived of food increased the concentration of two amino acids, phenylalanine and tyrosine, which control production of two brain neurotransmitters, norephinephrine and dopamine. However, Dr. Wurtman did not demonstrate that these biochemical changes produced behavioral changes in humans or animals. In addition, another study, cited by the FDA in the preamble to the carbonated beverage approval, 48 Fed.Reg. 31379, found that high doses of aspartame did not significantly influence the amounts of either neurotransmitter in the brains of the subjects. Second, Dr. Wurtman was concerned that aspartame would interfere with the production of another neurotransmitter, serotonin, that normally occurred when sated rats were fed large amounts of carbohydrates. Dr. Wurtman asserted that aspartame's effect on neurochemical activity in the brain had previously been estimated without consideration of the effect of carbohydrates. Dr. Wurtman maintained that aspartame's effects could be markedly amplified when the sweetener was ingested with carbohydrates that consumers probably would consume at the same time as carbonated soft drinks. However, Dr. Wurtman failed to provide empirical support for his hypothesis that aspartame interferes with carbohydrates' usual effect of inducing serotonin production. The Commissioner evaluated this study, and concluded that the agency had fully evaluated all the issues about the safe use of aspartame in carbonated beverages. 39 Appellants also cite an assertion by Dr. Paul LeChance that the increased use of aspartame resulting from the addition to carbonated beverages may result in a narrowed margin of safety between what could be labeled psychological levels of amino acids in a population known to consume high protein diets, and pharmacological levels with the possibility of exerting excitatory [sic] over time, and possible brain lesions.... The FDA concluded that an adequate margin of safety exists between the levels of phenylalanine [a component of aspartame] known to produce mental retardation and those resulting even from exaggerated exposure to aspartame in carbonated beverages. 49 Fed.Reg. 6674. 40 2. Nitrosamines. Nitrosamines, believed to be carcinogenic, are compounds that theoretically might result from the breakdown of aspartame and of diketopiperazine (DKP), a breakdown product of aspartame. The agency, however, basing its findings on Searle experiments which attempted to create nitrosamines under ideal laboratory conditions, concluded that stable nitrosamines were extremely difficult to form, and that any amounts that could be formed were extremely unstable under conditions that would occur in the gastrointestinal system. Id. at 6674, 6677. Appellants have argued that the FDA should reopen the search for carcinogenic nitrosamines, citing the emergence of new analytical techniques since 1974 that enabled investigators to detect nitrosamine in malt beverages. We conclude that the FDA acted well within its discretion in concluding, based upon its expert review of the record, that Appellants offered no evidence that the formation of nitrosamines in malt beverages has any possible relevance to structurally dissimilar nitrosamine formation in soft drinks containing aspartame. Id. at 6677. Absent proof by Appellants that new scientific procedures were relevant to beverages containing aspartame, FDA could as a matter of policy decide against requiring additional testing without holding a hearing on the issue. 41 3. Increased Consumption. Appellants maintain that the FDA's previous estimates of daily aspartame consumption, which formed the basis for its conclusion that dry use of aspartame was safe, cannot form the basis for approval of aspartame in wet uses without a hearing. The premise of Appellants' argument is that wet use will increase the overall average consumption of aspartame. Our review of the record convinces us that the FDA gave proper consideration to the effect of liquid use on overall consumption in concluding that the public would not be exposed to danger. In its hearing on dry use of aspartame, the Public Board of Inquiry used the consumption estimate of 34 mg of aspartame/kilogram (mg/kg) of body weight as the 99th percentile of estimated daily consumption for all age groups. 46 Fed.Reg. 38289-90. This estimate means that only one percent of those who consume aspartame would consume more than 34 mg/kg a day, while the vast majority of consumers would have lower consumption levels. Significantly, this 34 mg/kg figure was based on the assumption that aspartame would be used in the foods sought for approval in the dry use petition, in a number of other foods, and as the only sweetener in all carbonated beverages. Id. at 38285, 38290. The FDA also projected that an average daily intake of 50 mg/kg of body weight would be safe. 49 Fed.Reg. 6672, 6677, 6679. Since the FDA observed that the no effect dose for aspartame (the highest level at which no toxic effects on experimental animals were observed) was between 2000 and 4000 mg/kg of body weight, the agency concluded that a 50 mg/kg intake body weight was safe. The safety factor, between forty-fold and eighty-fold, provides a conservative safety margin; it indicates that the average daily consumption could be multiplied by that factor without exceeding the no effect dose of aspartame. Id. at 6677-78. Appellants also allege that some patterns of consumption of carbonated beverages--for example, drinking several cans in rapid succession on a hot day--would lead to higher concentrations of aspartame. The FDA acknowledged that some consumers may exceed 34 mg/kg of aspartame on some days, particularly consumers in hot weather or consumers, such as children, who have low body weight. 49 Fed.Reg. 6678. The agency, however, noted that studies conducted by Searle Laboratories, intervenors/respondents in this case, indicated that even levels of 200 mg/kg of body weight in a single dose did not produce acute toxicity. This concentration is the level that would result from a normal adult's consumption of 5.5 pounds of sugar or 13 quarts of orange soda containing aspartame in a single sitting. 48 Fed.Reg. 31380; 49 Fed.Reg. 6676. The FDA could properly exercise its discretion in deciding that the pattern of aspartame ingestion over the day is not important as long as the total amount ingested per day does not exceed the 200 mg/kg level shown to be safe. 49 Fed.Reg. at 6678. We find no reason to disturb this conclusion. 42 4. Carcinogenicity. Appellants attempt to reopen the issue of the carcinogenicity of aspartame and its breakdown products. Although the Commissioner concluded, based on the dry use proceeding, that aspartame had not been shown to cause cancer, Id. at 6672, 6679-80, Appellants challenge this conclusion by attacking one of the studies that provided support for the Commissioner's conclusions. No party contested the agency's reliance on the study during the dry use proceeding. Nor do Appellants point to specific deficiencies in the study which have come to light since the time for appeal expired. We find that Appellants have failed to create a material issue on the carcinogenicity of aspartame that the agency overlooked in its decision to deny a hearing in this case. 43 5. Labeling Requirements. Appellants assert that the conditions of use and required labeling statements for aspartame in liquid use are new issues that the Public Board of Inquiry did not address. The Board and the FDA, however, have considered the issue of appropriate warnings. The Board required a caution to patients with phenylketonuria that aspartame contained phenylalanine. In addition, the Commissioner's dry use approval in 1981 required a statement on the label that aspartame, when packaged as a tabletop sweetener, should not be used in cooking or baking. 21 C.F.R. Sec. 172.804(e)(3). Appellants' current objections do not present any new evidence or suggest any material issue of fact about the necessity of additional warning or labeling requirements. 44 Appellants also raise a number of issues which they maintain are unique to wet use and therefore were properly excluded from the dry use studies. Specifically, Appellants claim that wet use of aspartame 1) has a toxic effect on human embryos; and 2) decomposes at higher temperatures in a more dangerous way than aspartame carried in dry mediums. We find no evidence on either of these points that would require the FDA to hold a hearing. 45 1. Danger to Fetuses. Diketopiperazine (DKP) is the principal degradation product of aspartame. Seeking to prove the embryotoxic effects of DKP, Appellants advance a letter from Dr. Jean Lederer, reporting on his administration of DKP to rats. The FDA weighed this evidence, and concluded that aspartame and its breakdown products did not produce fetal damage. 49 Fed.Reg. 6682. Dr. Lederer could not associate fetal damage with aspartame, 48 Fed.Reg. 31380. In its approval of July 8, 1983, the FDA concluded from Dr. Lederer's report, Aspartame and its Effect on Gestation in the Rat, that animals fed at the highest level of DKP in the diet showed no embryotoxic effects. 46 2. Decomposition. Appellants argue that the use of aspartame in carbonated beverages is qualitatively different from its use in dry foods. They base this argument on the claim that carbonated liquid is peculiarly susceptible to changes of temperature and quality of the medium that lead to the breakdown of a large amount of the aspartame present in the liquid. In addition, Dr. LeChance asserted that the presence of carbonated beverages in distribution channels in subtropical temperature conditions during the summer months would lead to deterioration of DKP and release of the free amino acids.... It was within the FDA's discretion to conclude, based on its expert review of the evidence, that no safety issues respecting aspartame's instability at high temperatures warranted a hearing. 48 Fed.Reg. 31376-77, 31381. 47 We conclude that Appellants have failed to raise any material issues of fact requiring the FDA to grant a hearing. Therefore, we affirm the FDA's decision in Case No. 84-1153 to deny Appellants a hearing on the wet use of aspartame. In Case No. 84-5253, we affirm the District Court's dismissal for lack of jurisdiction of Appellants' request for a stay of approval pending the hearing. 48 It is so ordered.