Medical foods are a growing segment of the food industry; an estimated $8 billion worth was sold world-wide in 2011, $2 billion of which represents U.S. sales.1 Industry watchers expect continued growth in this niche food category as the U.S. population ages into nursing homes. The industry itself is defined but relatively lightly regulated by the Food and Drug Administration (FDA), and, within the rules, a medical food company can market its product for use in managing specific diseases without falling under FDA’s more stringent drug requirements. However, as explained in an April 11, 2013 Warning Letter to Realm Labs, LLC, FDA considers the statutory definition of "medical food" to narrowly constrain the types of products that fit within this category.
Before 1972, FDA regulated medical foods as drugs intended chiefly for patients with inherited metabolic diseases. One of the first products marketed for this purpose was Lofenalac®, an infant formula that FDA approved in 1957 as a new drug product under FFDCA §201(g)(1)(B) for the dietary management of phenylketonuria (PKU).
Following the 1962 amendments to the Federal Food, Drug, and Cosmetic Act (FDCA)2, FDA reclassified enterally provided products as foods for special dietary use, but kept injectable medical foods classified as drugs subject to the agency’s Drug Efficacy Study Implementation (DESI) program. Thus, nutrition administered enterally (e.g., ingestion through the digestive tract) moved to the food category, while parenteral nutrition administered by injection retained its drug status.
FDA made the change because the category of foods for special dietary purposes was well-established,3 few such products were marketed at the time,4 and the cost of obtaining new drug approval would have been prohibitive. However, the foods were available only under the supervision of a physician who diagnosed and managed the disease condition which the food was intended to help treat.
In 1973, Ross Products, a division of Abbott Nutrition, introduced Ensure, which was designed for either tube feeding or oral supplementation. Ensure is reported to be the first intact-nutrient, lactose-free, ready-to-use adult medical nutrition product in the U.S., an all-purpose product designed for tube feeding and oral supplementation; Glucerna®, developed in 1989 by Ross Products for patients with diabetes, was reportedly the first enteral formula to be patented; and Pedialyte® for rehydration was one of the first retail medical foods for children.5
In 1988, the Orphan Drug Amendments to the FDCA formally defined "medical food" as "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."6 In the Nutrition Labeling and Education Act of 1990 (the 1990 NLEA amendments, P.L. 101-535), Congress incorporated the definition of medical foods contained in the Orphan Drug Amendments of 1988 into section 403(q)(5)(A)(iv) of the Act (21 U.S.C. §343(q)(5)(A)(iv)) and exempted medical foods from the nutrition labeling, health claim, and nutrient content claim requirements applicable to most other foods. FDA’s implementing regulation at 21 CFR §101.9(j)(8) sets forth criteria to clarify the statutory definition of a medical food.
Specifically, 21 C.F.R. §401.9(j)(8)(i)-(v) provides that a food is a medical food only if:
- It is a specially formulated and processed product (as opposed to a naturally occurring foodstuff used in its natural state) for the partial or exclusive feeding of a patient by means of oral intake or enteral feeding tube;
- It is intended for the dietary management of a patient who, because of therapeutic or chronic medical needs, has limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who has other special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone;
- It provides nutritional support specifically modified for the management of the unique nutrient needs that result from the specific disease or condition, as determined by medical evaluation;
- It is intended to be used under medical supervision; and
- It is intended only for a patient receiving active and ongoing medical supervision wherein the patient requires medical care on a recurring basis for, among other things, instructions on the use of the medical food.
Clarifying Distinctions between Medical Food and Food for Special Dietary Purposes
In 1996, FDA issued an Advance Notice of Proposed Rulemaking (ANPR) on the Regulation of Medical Foods in which it proposed to reevaluate medical food regulation and to clarify the differences between medical foods and foods for special dietary purpose.7 Although that ANPR was among ANPRs proposed for withdrawal in 2003,8 and withdrawn in 2004, it remains the basis of the agency’s views on medical food products.9
"Distinctive Nutritional Requirements"
In the ANPR, FDA addressed the chief differences between medical foods and foods for special dietary purpose, beginning with the meaning of "distinctive nutritional requirements" for which medical foods are intended:
Medical foods are foods that are formulated to aid in the dietary management of a specific disease or health-related condition that causes distinctive nutritional requirements that are different from the nutritional requirements of healthy people. Foods for special dietary use, on the other hand, are foods that are specially formulated to meet a special dietary need, such as a food allergy or difficulty in swallowing, but that provide nutrients intended to meet ordinary nutritional requirements. The special dietary needs addressed by these foods do not reflect a nutritional problem per se; that is, the physiological requirements for nutrients necessary to maintain life or homeostasis addressed by foods for special dietary use are the same as those of normal, healthy persons. These foods are formulated in such a way that only the ingredients or physical form of the diet is different.10
Alternatively, FDA stated that the distinctive nutritional requirement for which medical foods are formulated could also encompass physical or physiological limitations in a person’s ability to ingest or digest conventional foods, as well as distinctive physiological nutrient requirements. For example, this would include patients with limited or impaired ability to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who have other special medically-determined nutrient requirements. This definition of "distinctive nutritional requirements’’ would include:
[F]oods intended for persons not able to ingest foods in certain physical forms (e.g., solid food), foods intended for persons who need a concentrated form of nutrition because of reduced appetite as a result of disease or convalescence), or foods intended for persons who may have other physical limitations on the amount or composition of food that they can consume. Although these types of conditions do not necessarily result in nutrient needs different from those of healthy persons, they represent a situation where it may be necessary that the food be formulated and manufactured within very narrow tolerances to ensure that the food provides most or all of the essential nutrients, as the persons for whom the food is intended may not be able to eat a variety of foods to ensure that they meet their nutrient requirements.11
"Under the Supervision of a Physician"
Second, FDA clarified that "under the supervision of a physician’’ means that the intended use of a medical food is for the dietary management of a patient receiving active and ongoing medical supervision (e.g., in a health care facility or as an outpatient). Thus:
Medical foods are foods that are an integral component of the clinical management of a patient. Medical foods are not foods simply recommended by a physician as part of an overall diet designed to reduce the risk of a disease or medical condition, to lose or maintain weight, or to ensure the consumption of a healthy diet. Foods recommended by a physician for these purposes may be foods for special dietary use, but they are not medical foods.12
"Specific Dietary Management"
Finally, FDA stated that the term "specific dietary management’’ in the statutory definition of medical foods means that Congress intended these foods to be an integral part of the clinical treatment of patients:
Consistent with this interpretation of this term, the LSRO/FASEB Panel concluded that the objectives of incorporating the use of medical foods into patient management were, in part, to "ameliorate clinical manifestations of the disease," "favorably influence the disease process," and "positively influence morbidity and mortality (patient outcomes)." There is no language corresponding to "specific dietary management" in the statutory definition applicable to foods for special dietary use. Thus, although they may be useful in supplying the special dietary needs of patients who have a disease or other condition that prevents them from eating normally, foods for special dietary use, unlike medical foods, are not specifically tailored for use as the nutritional component of the patient’s treatment.13
FDA Enforcement of Medical Food Status
As explained in an April 11, 2013 Warning Letter to Realm Labs, LLC, FDA considers the statutory definition of "medical food" to narrowly constrain the types of products that fit within this category. FDA told Realm Labs that:
While your labeling states that the patients for whom your NeuRemedy products are intended have low levels of the micronutrient thiamine, FDA is not aware of any evidence that patients with neuropathy have a limited or impaired capacity to ingest, digest, absorb, or metabolize thiamine, or other nutrients, or have a distinct requirement for thiamine or any other nutrient….Because your NeuRemedy products are intended to support a condition, neuropathy, that does not have distinct requirements for certain nutrients, these products do not meet the regulatory criterion for medical foods.14
In other Warning Letters issued to medical food companies over the past decade, FDA has disallowed claims associated with fibromyalgia, chronic fatigue syndrome, and cardiovascular disease, 15 allergies and asthma,16 arthritis, irritable bowel syndrome, colitis, constipation, diarrhea, lactose intolerance,17 immune system deficiencies, Alzheimer’s disease,18 inflammatory conditions, migraines, chronic fatigue syndrome,19 failure to thrive, chronic illnesses, pre-post-surgery conditions,20 vitamin deficiency throughout pregnancy, postnatal and the lactating periods.21 In each of these cases, FDA took one or more of the following positions, that there was inadequate evidence that the disease had distinct nutritional requirements, or that the particular food at issue would meet the distinct nutritional requirements for the disease, or that no evidence is available showing that the nutrient levels cannot be achieved by modification of the normal diet alone.
Supporting Medical Food Claims
FDA’s Office of Nutrition, Labeling, and Dietary Supplements (ONLDS) is responsible for medical food labeling. In addition to improper marketing of foods as "medical foods," ONLDS is also concerned that claims for medical foods be properly supported. Thus:
It is not enough that a manufacturer merely declare or subjectively intend that the product be used for the dietary management of patients with certain diseases or conditions. If the product, as formulated and consumed, does not actually meet those distinctive requirements, it would violate the act. Under any other view, the medical foods category would merely create a safe harbor for fraudulent claims targeted at those who are most vulnerable.22
FDA proposed a substantiation standard for nutritional efficacy of medical foods somewhere between substantiation based upon "significant scientific agreement" (the totality of publicly available scientific evidence that qualified experts agree supports the claim) and "substantial evidence" based upon adequate and well-controlled investigations used to evaluate the effectiveness of a drug. FDA asked for comments on what that standard should be, and stated that its preliminary view was that the scientific standard contained in the statutory medical food definition may require some of the same types of data for medical foods as are needed to support drug claims (e.g., data from clinical investigations).23
Good Manufacturing Practices – Inspections and Imports
FDA’s Medical Foods Compliance Program (CP 7321.002) for domestic and imported products has been in effect since 1996 and is part of the agency’s Compliance Program Guidance (CPG) Manual.24 FDA identifies the compliance program for medical foods as "high priority" and states that the firms inspected and the products collected are considered high risk because of the susceptible population for which the products are intended. FDA estimates that growth of medical foods will continue to rise as the elderly population in and outside of nursing homes increases.
During inspections of medical foods facilities, FDA reviews labeling, promotional materials, brochures and correspondence with physicians, and collects samples of recent lots for microbiological and nutrient content analyses. FDA has compiled a list of known non-U.S. medical food manufacturers and their products and all imported and other shipments of medical foods not on FDA’s list "must be sampled and held" pending test results. FDA has also identified certain non-U.S. medical foods to be detained without physical examination under Import Alert # 41-03; 10/12/2011, "Detention Without Physical Examination of Adulterated and Misbranded Medical Foods."25 Firms may be listed on the Alert’s so-called "Red List" either because the most recent FDA inspection conducted revealed that the plant was not following good manufacturing practices described in 21 C.F.R. §110 or was otherwise preparing, packing, or holding products under insanitary or other conditions that could have rendered the products injurious to health, and/or because one or more products manufactured at the plant were analyzed by FDA and classified as violative. A firm might also appear on the Red List because the label misstates the active amount of an ingredient.
As the U.S. population ages and more people are in hospitals, nursing homes or lose the ability to eat or metabolize food normally, the need for medical foods is expected to continue to grow. Because medical foods are relatively lightly regulated by FDA, the barriers to market entry are lower than for other medical products. In fact, a recent article from Today’s Dietician26 suggests that medical foods are more widely marketed than the limited number of FDA Warning Letters over the past decade would imply. At present, FDA may trust that GMP inspections, import controls, website reviews, and the supervision of medical professionals that prescribe and manage the use of medical foods will be a sufficient control. However, medical foods available and promoted directly to the public at large, and especially through the Internet, present a higher risk and likely will be an FDA enforcement target. Moreover, one cannot predict what the FDA and public reaction might be to a situation involving medical food contamination on a scale recently experienced in the outbreak of fungal meningitis and other infections linked to injectable steroids from compounding pharmacies that to date has sickened over 800 persons and caused 58 deaths. This tragedy has led to over 30 FDA inspections and active Congressional involvement in new legislation to extend FDA’s authority over all but the most traditional compounding pharmacies.