Conflicts of interest in the regulation of food safety: a threat to scientific integrity.

Conflicts of interest inmedical research, education, andpractice arewell known to increase the risk of undue influence by corporate sponsors. Because conflicts of interest are soprevalent and troublesome, the Institute of Medicine (IOM) was asked to develop guidelines for dealing with them. An IOM committee reviewed the substantial body of evidence demonstrating that financial ties with pharmaceutical and medicaldevicecompanies influenceprescribingpractices; theopinions of experts; and the design, conduct, and interpretation of research studies. The guidelines produced by the IOM focus on financial connections with industry, largely because such connections are easier tomonitor than other conflicting interests, such as career advancement or personal favors.1 Although conflicts createdby financial relationshipswith drug anddevice companies have been a source of concern for decades, concerns about the effects of food company sponsorshiponnutrition research, practice, andpolicy aremore recent. Nevertheless, financial ties with food and beverage companies are now recognized as influences on federaldietaryguidelines,opinionsofnutritionprofessionals, and the interpretationofnutritionstudies.2 Investigatorshavedemonstrated impressive similarities between the actions of cigarette companies and food companies in promoting and protectingproduct sales.3Consistentwith theobservationsby the IOM,most studies sponsored by food or beverage companies support the benefits of the sponsor’s products, whereasmost independently funded studies do not.4 The study by Neltner and colleagues5 provides an important addition to the growing body of evidence for undue food industry influence on food safety policy. The study examined conflicts of interest among scientific experts serving on panels decidingwhether food additives—substances that preserve, flavor, blend, and thicken food—shouldbedeemedgenerally recognized as safe (GRAS) and exempt from Food and Drug Administration (FDA) premarket approval requirements.Their findingsarealarming.Anastonishing 100%of the membersof 290expertpanels included in their reviewworked directly or indirectly for the companies thatmanufactured the additive inquestion.Evenmorealarming, theexpertson these panels form a tight professional cadre. Although 850 people served on the panels, 10 experts served on 27 panels ormore, and one of these 10 participated in three-quarters of the panels.Thescientific substantiationusedbymanufacturers tosupport GRAS status is highly conflicted. This state of affairs might not matter if all food additives were safe at current levels of intake. But some are not. A few additives once assumed tobe safe, suchas cyclamate salts and sulfites, are nowbanned or no longer consideredGRAS.More recently, the FDA has issued warnings about caffeine in alcoholic beverages. Its decisions about the safety of GRAS substances suchas trans fats and salt havebeenpending for years. How is it possible that the FDA permits manufacturers to decide for themselves whether their food additives are safe? In 1958, Congress passed a law requiring companies introducing a new additive to provide evidence of safety before putting it on themarket.TheFDA’s subsequent regulationsdidnot requiremanufacturers to establish additive safetywith absolute certainty. But theydiddemand reasonable assurance that anadditivewasunlikely to causeharmunder conditionsof intended use. Becausemany additives had been in the food supply for a long timeandwereassumedtobesafe, the lawexemptedGRAS substances from premarket approval requirements. Thus, no FDA reviewwas required for additives thatmanufacturers believed qualified for a GRAS exemption. Because somemanufacturerswantedwritten reassurance that theFDAagreedwith theirGRASdecisions, theagencyallowedmanufacturers topetition for GRAS status.Many did, and the FDAwrote “opinion letters” in response. In 1997, the FDA responded to the Clinton administration’s “Reinventing Food Regulation” initiative by announcing that it planned to streamline the GRAS process as an incentive for manufacturers to inform the FDA about new additives. The agency proposed to replace the petition system with a simple notification process.9 Food companies could—at theirowndiscretion—notify theFDAthatexpertsgenerally agreed that anewadditivewas safe.Color additiveswere an exception;manufacturerswould still have to submit them to the FDA for premarket approval and provide evidence for safety. It is astonishing that these rules, proposed 16years ago, have never been issued in final form and are still pending. At present, manufacturers of all food additives are permitted todecideon their ownwhether a substance isGRAS for human consumption, unless the additive affects food color. Companies also can choosewhether to evennotify the agency about a new additive. In practice,manymanufacturers do inform theFDA. But, asNeltner et al5 explain, about a thousand additives are believed to be in the food supply without the FDA’s knowledge. For example, manufacturers added caffeine to alcoholic drinks without informing the FDA. The study by Neltner et al5 is based on review of the voluntary notification letters sent to the FDA. It is possible that expertpanels reject someproposedGRASexemptions,butsuch decisionswouldnever come to theFDA’s attention.When the FDA receives notification letters, it reviews and responds to them. The FDA has “no questions” about most notifications, thereby tacitly approving the additive as GRAS. However, approximately 15%of the letters arewithdrawn fromFDAevaluRelated article