A Major Obstacle in the Path of Clinical Nutrition Research
FOOD, MEDICINE & HEALTH
In September FDA issued Guidance for Clinical Investigators, Sponsors, and IRBs: Investigational New Drug Applications (INDs)—Determining Whether Human Research Studies Can Be Conducted Without an IND. This final Guidance significantly changed scope from the 2010 draft IND guidance that did not address foods. The new Guidance requires a wide range of studies including investigations establishing relationships between foods and structure/function or health outcomes to secure an IND. In effect, this mandates drug research standards for food studies.
The food manufacturing industry is one of America’s largest manufacturing sectors (U.S. Dept. of Commerce, 2008), yet there was no forewarning such a regulatory sea change for food research was coming. The potential impact is significant, ranging from adding new regulatory barriers and increased costs for product development to stifling U.S. research and innovation and incentivizing its movement abroad. Considering the global competitive marketplace, Congress recently expressed its own concerns about “foreign competitors acquiring decades of American innovation and food production technology” (Sen. Debbie Stabenow, D-Mich., 2013).
FDA cites no inadequacies about the previous process, which did not require an IND for food research but relied on Institutional Review Boards for the protection of human subjects. This Guidance adds significant burdens where there was no problem. All stakeholders, including the public, healthcare providers, academia, industry, and government need a chance for dialogue on how to best meet the ultimate goal of the IND regulations, which is ensuring the safety of clinical subjects. There is growing support within the food industry, among many scientific organizations, and leading clinical nutrition investigators from academic institutions that urges withdrawal of this new Guidance until there is an adequate opportunity for its open review and discussion of alternatives.
The Guidance states an IND is needed for clinical investigations that evaluate a food’s effect on the structure or function of the body that is not considered sensory-related or nutritive. Studies that evaluate the effect of a food or nutrient in a food on the structure or function of the body are central to advancing health through nutrition. Many substances in foods, from essential nutrients to bioactive components, specifically exhibit their nutritive value by affecting the structure or function of the body.
Even before this Guidance, an IFT Expert Panel recommended that FDA not “restrict the health effects of foods to the very limited concept of nutritive value,” arguing that structure/function and health claims need a foundation of broad-based scientific criteria that address the extensive links between health and nutrition and other scientific disciplines (IFT, 2005). Yet this Guidance actually further narrows the concept of “nutritive value” in its examples of which studies would and would not require an IND.
Food technology and nutrition research has changed dramatically since 1938 when the Federal Food Drug and Cosmetic Act (FFDCA) was enacted. “Food and nutrition science has moved from identifying and correcting nutritional deficiencies to designing foods that promote optimal health and reduce risk of disease” (IFT, 2005). The Dietary Guidelines encourage “Americans to focus on eating a healthful diet—one that focuses on foods and beverages that help achieve and maintain a healthy weight, promote health, and prevent disease” (USDA, 2010). Yet the challenge remains of how regulatory policies can be advanced to ensure the safety and efficacy of foods and accuracy of promotional claims, while balancing the inherent limitations of research on the complex matrixes of food and nutrition.
The FFDCA specifically defines both foods and drugs. If a product meets the definition of “food” and is intended to affect the structure/function of the body, and does not make a disease claim, then the product is expressly excluded from the statutory definition of “drug” (21 U.S.C. §321). IND regulations specifically are for investigational new drugs, not foods. The Guidance does not distinguish how to implement a drug level approach to food research. Drugs typically have only one or two active compounds and a small number of inert ingredients. In contrast, foods are typically complex matrixes of numerous compounds (both known and unknown) that can exhibit seasonal and regional variability.
Recently, a presidential advisory panel reviewing drug development and regulation highlighted the need for “greater clarity about the general regulatory pathways for innovative products and approaches” (President’s Council of Advisors on Science and Technology, 2012). Food manufacturers will likely be reluctant to invest in new research, given the complexities and unknowns of the now-required IND. There is also the question of the applicable Good Manufacturing Practice (GMP) standard for studies of foods under this new Guidance. Food manufacturing is required to comply with food GMPs (21 CFR 110) while drugs follow drug GMPs (21 CFR 211). In addition, under current regulations, once an ingredient has been studied as a drug, it can no longer be marketed as a food unless it was already marketed that way prior to drug studies being conducted. This Guidance creates a perverse incentive to commercialize products before completing clinical research programs, to assure that they can ultimately legally market the products as something other than a drug.
The FDA is “responsible for advancing the public health” (FDA, 2013). Requiring a drug-level approach to food research will limit new investigations and will not advance public health. Food and nutrition research should be expanded to explore the health role for foods, not hampered by oversight based on a framework developed for drugs.
References cited in this article are available from the author.
Roger Clemens, Dr.P.H., CFS,
Contributing Editor
Chief Scientific Officer,
Horn Company, La Mirada, Calif.
[email protected]