United States: Understanding Medical Foods Under FDA Regulations

11.1 HISTORY OF MEDICAL FOODS

It took the Food and Drug Administration (FDA) 50 years after the passage of the Federal Food, Drug, and Cosmetic Act (FDCA) to formally define "medical foods." Prior to 1972, what we now would consider medical foods were regulated as prescription drugs under section 201(g)(1)(B) of the FDCA because of their role in mitigating serious adverse effects of diseases.¹ Furthermore, prior to 1972, to market new products, manufacturers of medical foods were subject to onerous requirements, such as conducting complete drug trials, Investigational New Drug license applications, and New Drug Applications. Extremely time-consuming and cost-restrictive, such requirements choked the life out of medical food product innovation.

In 1972, the FDA reassessed its position on medical foods. This action was prompted by the agency's interest in fostering innovation in the development of medical foods and ensuring that such products were available to the public at a reasonable cost. However, due to safety concerns, the agency still sought to differentiate medical foods from general use foods. For example, the FDA reasoned that Lofenalac, an infant product designed for use in the dietary management of a rare genetic condition known as phenylketonuria (PKU), would be hazardous for healthy infants since it would be nutritionally inadequate for them. Therefore, the agency reclassified medical foods provided enterally (i.e., ingested via the digestive tract) as "foods for special dietary use," but injectable medical foods remained classified as drugs subject to the FDA's Drug Efficacy Study (DESI) program.² In short, enterally administered nutrition was transferred to the food category while parenteral nutrition (i.e., injected into the body) retained its drug status.

Just one year later, when the agency made nutrition labeling mandatory for certain foods, it exempted certain types of foods for special dietary use from this requirement.³ In the preamble of the final rule, the FDA noted that nutrition labeling developed for foods intended for consumption by the general population was not well suited for some food products. Two foods for special dietary use were exempted from the nutrition labeling required for other food: (1) any food represented for use as the sole item of the diet and (2) foods represented for use solely under medical supervision in the dietary management of specific diseases and disorders.

A statutory definition of medical foods was finally promulgated in the Orphan Drug Amendments of 1988, Section 5b, Orphan Drug Act.⁴ A medical food was defined 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."⁵ This statutory definition remains unchanged. Unfortunately, the legislative history of the amendments does not discuss the statutory definition of medical foods, thus failing to provide any additional information regarding the types of products Congress intended the definition to cover.⁶

Soon after the Orphan Drug Act Amendments, the FDA formally launched its initiative to improve the content and format of food labels with the publication of an Advanced Notice of Proposed Rulemaking (ANPR).⁷ As part of this overall initiative, the agency sought to resolve consumer confusion about food labels, aid consumers in health food decisions, and encourage product innovations so that manufacturers were given an incentive to improve the quality of the food and provide consumers with more healthy food choices.⁸ In the ANPR, the FDA asked the industry for guidance on a wide range of food-labeling issues to assist the agency in determining what, if any, changes to food labeling requirements were necessary, and it was quickly followed by four public hearings. With obvious public support for a thorough modernization of food labeling, the FDA published proposed regulations on July 19, 1990.⁹

It was during the comment period for the proposed regulations that Congress passed the Nutrition Labeling and Education Act of 1990 (NLEA), and on November 8, 1990, the legislation was signed into law by President George H. Bush. Not only did the NLEA affirm the FDA's authority to mandate nutrition labeling on most foods and clarify the agency's role in regulating nutrient content claims and health claims on food labels, it also incorporated the definition of medical foods contained in the Orphan Drug Amendments of 1988 into Section 403(q)(5)(A)(iv) of the FDCA and exempted medical foods from the nutrition labeling, health claim, and nutrient content claim requirements applicable to foods generally.¹⁰

Quickly thereafter, the FDA published a proposal to implement the mandatory nutrition labeling provisions of the NLEA, focusing specifically on the statutory exemption for medical foods.¹¹ The proposal advised that the agency considered the statutory definition of medical foods to "narrowly constrain the types of products that can be considered to fall within this exemption,"¹² a sentiment that the FDA has since reiterated time and again. Further, the FDA explained how medical foods are distinguished from the broader category of foods for special dietary use and from foods that make health claims. In the FDA's opinion, "under the supervision of a physician" within the NLEA meant "that the intended use of a medical food is for the dietary management of a patient receiving active and ongoing medical supervisions (e.g., in a health care facility or as an outpatient). The physician determines the food that is necessary to the patient's overall medical care,"¹³ and the patient visits the doctor for instructions on the use of the medical food. In its closing remarks on medical foods, the FDA stressed the vital public health interest in proper labeling of the nutrient content and purported uses of medical foods, which it noted may require a different manner and more detail than more traditional foods, adequate and appropriate directions for use, and product quality assurance. Thus, the agency declared that it intended to develop regulations covering these aspects "in the near future."¹⁴

In the Federal Register of January 6, 1993, the FDA published the final rule on mandatory nutrition labeling, which exempted medical foods from the nutrition labeling requirements and incorporated the statutory definition of medical foods into the agency's regulations at Section 101.9(j)(8).¹⁵ In the regulation, the FDA enumerated criteria intended to clarify the characteristics of medical foods. Accordingly, a food was defined as a medical food and, thus, not subject to the nutrition labeling requirements only if:

1. 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.
2. 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.
3. 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.
4. It is intended to be used under medical supervision.
5. 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.¹⁶

This definition remains unchanged. In addition, the agency acknowledged that further clarification on the specific types of products the FDA considers medical foods would be helpful. Accordingly, it expressed its intention to address the issue in the future, but also noted its objective to develop much-needed medical food-labeling regulations.¹⁷

Citing the enactment of a statutory definition of medical food, the rapid increase in the variety and number of products marketed as medical foods, safety problems associated with the manufacture and quality control of these products, and the potential proliferation of fraudulent claims not supported by sound science, the FDA issued an ANPR on the "Regulation of Medical Foods" in 1996.¹⁸ The agency also sought to clarify the distinct differences between medical foods and foods for special dietary purpose. Though this ANPR was withdrawn in 2004, it largely remains the guiding force for industry understanding of the agency's views of medical food regulation.¹⁹

In the 1996 ANPR, the FDA acknowledged that the universe of products purporting to be medical foods had surpassed the statutory definition of a medical food to include foods that would more appropriately be categorized as foods for special dietary use. Looking to statutory language, the FDA sought to outline distinctions between these two types of foods, beginning with the meaning of "distinctive nutritional requirements" in the FDCA's definition of medical food. Pursuant to the statute, distinctive nutritional requirements must be based on recognized scientific principles and established by medical evaluation. Unfortunately, as the FDA noted in the ANPRM, the law does not define distinctive nutritional requirements. As a result, the agency proposed two possible interpretations of the phrase: (1) physiological interpretation and (2) alternative interpretation.

In the physiological interpretation, the FDA advised that distinctive nutritional requirements could be understood as referring to the body's need for specific amounts of nutrients to maintain homeostasis and sustain life. Under this interpretation, medical foods are

On the other hand, the agency stated in the alternative interpretation that distinctive nutritional requirement may be construed to encompass physical and physiological limitations in a person's ability to ingest or digest conventional foods, as well as distinctive physiological nutrient requirements.²¹ Similarly, the Life Sciences Research Office of the Federation of American Societies for Experimental Biology (LSRO/FASEB Panel) noted in its 1990 Guidelines for the Scientific Review of Enteral Food Products for Special Medical Purposes that medical foods are for "patients with limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients contained therein, or (who) have other specialized medically determined nutrient requirements."²² After quoting this purpose, the FDA stated that the definition of distinctive nutritional requirement would include

The second element that the FDA recognized as a distinguishing attribute of medical foods is the statutory requirement that a medical food be "formulated to be consumed or administered enterally under the supervision of a physician." As a general requirement, the patient must be receiving short- or long-term "active and ongoing" medical supervision (e.g., in a health care facility or as an outpatient).²⁴ Unlike foods for special dietary purposes, the FDA views medical foods as an integral component of the patient's clinical management. Medical foods are not just simply recommended by a physician as a "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."²⁵

The final fundamental element of the definition of medical food addressed in the 1996 ANPR is the statutory requirement that a medical food be intended for the "specific dietary management" of a disease or condition. The FDA advised that the term "specific dietary management. . .evidences that Congress intended [medical] foods to be an integral part of the clinical treatment of patients."²⁶ The agency also cited the LSRO/FASEB Panel's conclusion that the objective of incorporating the use of medical foods into patient management was, in part, to "ameliorate clinical manifestations of the disease," "favorably influence the disease process," and "positively influence morbidity and mortality (patient outcomes)."

Axona is an example of a medical food widely prescribed by physicians today. Axona, developed by Accera, is a medical food to provide the necessary nutrients for patients with Alzheimer's disease (AD). It has been clinically shown to improve cognitive function in some patients with AD, the leading cause of dementia, and does not increase metabolism. AD is a neurodegenerative disease characterized by a decline in the ability of the brain to metabolize glucose, even in its early stages. Axona is made from caprylic triglyceride and other medium chain triglycerides, which are converted to ketone bodies by the liver, an alternative energy source for cerebral neurons.

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Originally published in the Nutraceutical and Functional Food Regulations in the United States and Around the World (Second Edition).

Footnotes

1 Advanced Notice of Proposed Rulemaking, Regulation of Medical Foods, 61 Fed. Reg. 60661, 60662 (Nov. 29, 1996).

2 The FDA recognized foods for "special dietary use" as early as 1941. Per regulation, the FDA stated that the term "special dietary uses" as applied to food for man, meant, among other things, "uses for supplying particular dietary needs which exist by reason of a physical, physiological, pathological or other condition, including but not limited to the conditions of disease, convalescence, pregnancy, lactation, allergic hypersensitivity to food, underweight, and overweight." Amendment to the General Regulations, Regulations for the Enforcement of the Federal Food, Drug, and Cosmetic Act, 6 Fed. Reg. 5921 (Nov. 22, 1941). This part of the regulation remains unchanged in the Code of Federal Regulations. See 21 C.F.R. y 105.3(a)(1) (September 17, 2013).

3 8 Fed. Reg. 2124, 2126 (January 19, 1973).

4 21 U.S.C. y 360ee(b)(3). Foods for special dietary use were often referred to as "orphan" because they were developed for the treatment of rare disorders that affect fewer than 200,000 persons in the United States. T.P. Labuza, Food Laws and Regulations: The Impact on Food Research, 36 Food Drug Cosmetic L.J. 293 (1981).

5 21 U.S.C. y 360ee(b)(3). The amendments also introduced a subcategory called "orphan medical foods" to be used in the management of ". . .any disease or condition that occurs so infrequently in the United States that there is no reasonable expectation that a medical food for such a disease or condition will be developed without assistance." Id.

6 61 Fed. Reg. 60662.

7 54 Fed. Reg. 32610 (August 8, 1989).

8 Virginia Wilkening, The Nutrition Labeling and Education Act of 1990 (November 27, 1991), http://www.nutrientdataconf.org/PastConf/NDBC17/8-2_Wilkening.pdf (last visited September 17, 2013).

9 55 Fed. Reg. 29456 (July 19, 1990).

10 Nutrition Labeling and Education Act y 2(a)(1990).

11 56 Fed. Reg. 60366 (November 27, 1991).

12 Id. at 60377.

13 Id.

14 Id., at 60378

15 58 Fed. Reg. 2079, 2151 (January 6, 1993).

16 21 C.F.R. y 101.9(j)(8).

17 58 Fed. Reg. 2151.

18 61 Fed. Reg. 60662.

19 69 Fed. Reg. 68834 (November 26, 2004). The FDA declared that: Because of competing priorities that have tied up FDA's limited resources, the agency has been unable to consider, in a timely manner, the issues raised by comments on the ANPRM, and does not foresee having sufficient resources in the near term to do so. Therefore, the agency is withdrawing this ANPRM. However, FDA believes that the basic principles described in the ANPRM provide an appropriate framework for understanding the regulatory paradigm governing medical foods. Therefore, FDA advises that it will continue to refer to the basic principles described in the ANPRM and in FDA's Medical Foods Compliance Program (CP 7321.002) when evaluating medical foods. With regard to the specific points made in the comment regarding regulation of medical foods, the comment is correct that the act exempts medical foods from the nutrition labeling, health claim and nutrient content claim requirements that are applicable to most other foods. However, all statements on food labels (including medical foods) must be truthful and not misleading (see section 403(a)(1) of the [A]ct). FDA advises that medical foods with false and misleading labeling are subject to enforcement action. The agency also advises that withdrawal of this ANPRM does not change the requirement that all ingredients used in medical foods must be approved food additive, GRAS, or otherwise exempt from the food additive definition. Medical foods that do not comply with this requirement are subject to enforcement action.

20 61 Fed. Reg. at 60667. The agency provided an example of a person possessing a special dietary need for a food that is in liquid form due to problems swallowing, noting that this special dietary need does not change his or her physiologic nutrient requirements. Along the same lines, a person allergic to gluten may need foods specially formulated, but the food would still provide the same amount of amino acids as needed by the general population because the quantitative and qualitative amount of overall protein required by the body is similar in both healthy and protein-sensitive individuals. Id.

21 Id.

22 J.M. Talbot, Guidelines for the Scientific Review of Enteral Food Products for Special Medical Purposes, Life Sciences Research Office, Federation of American Societies for Experimental Biology (1990).

23 61 Fed. Reg. at 60668.

24 Id. (citing 56 Fed. Reg. 60377).

25 Id., at 60668.

26 Id.

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