Every day there is news about advances in nutrition science. We are learning more about the role of nutrition, dietary components and bioactive compounds in health and disease processes. People with diseases and conditions that initially could only be addressed through drug therapies may now benefit from dietary management of those conditions as well. Of course, FDA has made it clear that dietary supplements are intended for use by healthy individuals. However, there is an avenue for nutritional products that have a role in the dietary management of a disease or its metabolic processes: the regulatory category of “medical foods.”

Over the last two years the volume of our consulting activities at Windrose Partners has seen a rather dramatic increase in projects related to the medical food market. In this month’s Business Insights column I have invited two Windrose Associates, Sheila Campbell, PhD, RD, and Sandy Bigelow, PhD, to assist in addressing a key, and sometimes confusing, aspect of medical food regulations: the significant scientific agreement dossier supporting claims.

A Regulatory Primer
The concept of specially formulated foods for seriously ill patients is certainly not new. These special foods were developed as early as the 1940s and FDA proposed its first definition for Foods for Special Dietary Use (FSDU) in 1941. Prior to 1941 the agency regulated these types of products as drugs. The 1988 Orphan Drug Amendments provided the first statutory definition of the term “medical food” as follows: “A food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation,” (21 U.S.C. 360ee(b)(3).

The size of the medical foods market remains difficult to estimate. Windrose Partners estimates the U.S. market at $3 billion. The majority of sales are to healthcare institutions—hospitals, nursing homes and home care agencies. Increasingly, medical foods are being marketed direct to health practitioners and even distributed through retail channels, still requiring they be used under medical supervision. The market is projected to continue low double-digit growth over the next few years, driven primarily by the aging population and advances in nutrition science.

By definition, when used to provide dietary management, medical foods must provide “medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone,” (21 CFR 101.9(j)(8)). Unlike drugs, medical foods do not require years of costly product safety and efficacy testing and FDA premarket approval. Consequently, medical foods are gaining importance as cost-effective components of disease management. Bear in mind though, approval of claims for medical foods requires that a credible case is made that the medical food has scientific rigor and consistency with regulatory requirements through medical evaluation.

The 1990 Nutritional Labeling and Education Act (NLEA) required FDA to issue regulations authorizing the use of a health claim only when evidence demonstrated that “significant scientific agreement” (SSA) was met. Significant scientific agreement is the quality and quantity of evidence FDA defines as sufficient to demonstrate agreement by qualified experts regarding the claim. Health claims are intended for labeling of foods and supplements consumed by healthy people. Medical foods are intended to address management of diseases through consumption by patients under the care of a healthcare practitioner.

Substantiating claims requires development of a scientific dossier demonstrating a specific disease or medical condition has distinct nutritional needs that cannot be otherwise met through modification of the diet alone. It is insufficient to state the product works nutritionally if the scientific literature does not show the medical food components are necessary. However, neither the NLEA nor FDA specified the content or appearance of an acceptable SSA.

In 1999, FDA issued “Guidance for Industry: Significant Scientific Agreement in the Review of Health Claims for Conventional Foods and Dietary Supplements.” This document clarified the agency’s interpretation of SSA but still did not clearly define the meaning of the term. In 2009, FDA issued guidance outlining its approach to evaluating scientific evidence for health claims. Petitions for health claims undergo both a scientific and a regulatory review. 

SSA Dossier Contents to Support Health Claims
The most important scientific document a petitioner can have is an SSA dossier. Ideally, the person developing the SSA document has academic and clinical expertise. The ideal person to develop this document is a person knowledgeable and experienced in searching, reading, dissecting and interpreting the literature. Select someone who has a researcher-level understanding of the following issues and ability to apply them in a clinical context:

• Research question development
• Study design
• Appropriate study population and sample size
• Data collection methods
• Statistical test selection
• Data analysis
• Interpreting findings

The SSA consists of a thorough, comprehensive and objective review of the medical and scientific literature defining the substance/disease relationship, and answers these critical questions:

• Have the studies specified and measured the substance that is the subject of the claim?
• Have the studies appropriately specified and measured the specific disease or health-related condition that is the subject of the claim?
• What is the type of study and is it appropriate to answer the question (e.g., intervention studies, prospective and retrospective, observational studies, research synthesis studies, animal and in vitro studies)?
• Were appropriate outcomes and surrogate endpoints identified and used?
• Were the appropriate study population and sample size identified and used?
• Were study methods appropriate?
• Were the data appropriately collected and analyzed?
• Was the study site and length appropriate to collect meaningful data?
• Were the study results appropriate to the U.S. population?

The SSA defined two elements: 1) consensus requirement and 2) evidence requirements (as implied, if the questions are answered properly). Even though SSA is not a statutory mandate for determining the adequacy of the evidence for claims used in medical food labeling, the evidence requirements of SSA elaborated here can help to define a framework for assembling the scientific and clinical evidence for such labeling. 

Clearly, SSA denotes a form of consensus in the community of scientists to agree that a claim is supported. FDA has often used conclusions of the Institute of Medicine, Life Sciences Research Office and the American Society of Nutritional Sciences (both of the Federation of American Societies for Experimental Biology, FASEB), and the American Academy of Pediatrics as a basis to form SSA. SSA does not require consensus to the degree of unanimity or even a putative agreement among scientists, whereas a consensus of the majority of scientists may be debatable. 

For medical foods, especially for conditions in which few patients are afflicted (e.g., inborn errors of metabolism), reaching significant scientific agreement is difficult at best because so few scientists/clinicians are knowledgeable of the condition(s) studied. Thus, the evidence requirements for SSA may be useful for assembling the information required to substantiate medical food claims. Medical foods are developed through medical evaluation based on recognized scientific principles (21 U.S.C. 360ee(b)(3), 21 CFR 101.9(j)(8)). Many of the evidence requirements, in the form of questions, elaborated above incorporate recognized scientific principles. 

The benefits of medical foods, substantiated by sound clinical research, are increasingly understood and supported by physicians and other health practitioners. As the science continues to drive innovation the market will grow. FDA has defined this regulatory category offering health practitioners the products and educational tools necessary to address the dietary management of some serious health conditions. It is up to the industry to meet and exceed the regulatory and scientific standards these patient populations require and deserve. 

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Gregory Stephens
Greg Stephens is president of Windrose Partners, a company serving clients in the the dietary supplement, functional food and natural product industries. Formerly vice president of strategic consulting with The Natural Marketing Institute (NMI) and vice president of sales and marketing for Nurture, Inc (OatVantage), he has 25 years of specialized expertise in the nutritional and pharmaceutical industries. His prior experience includes a progressive series of senior management positions with Abbott Nutrition (Ross Products Division of Abbott Laboratories), including development of global nutrition strategies for disease-specific growth platforms and business development for Abbott’s medical foods portfolio. He can be reached at 267-432-2696; E-mail: gregstephens@windrosepartners.com.

Sheila Campbell
Sheila Campbell, PhD, RD, has practiced in the field of clinical nutrition for more than 30 years, including 17 years with Ross Products Division of Abbott Laboratories. She has authored more than 70 publications on scientific, clinical and medical topics and has presented 60 domestic and international lectures on health-related topics. She can be reached at smcampbellphdrd@gmail.com.

Sandy Bigelow
Sandy Bigelow, PhD, principal, Vanguard Global Associates LLC, is a research and development professional with more than 20 years of experience in leading global technology responsibilities in the food, nutrition and medical device industries. He can be reached at sandy@vanguardglobalassociates.com.