The Food and Drug Administration (FDA) has proposed an update to its May 2007 draft guidance titled, “Draft Guidance for Industry: Frequently Asked Questions About Medical Foods (Second Edition)”.1
Medical food is defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C. § 360ee(b)(3)) as “a food which is formulated to be consumed or administered entirely 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.” 2
This revision to the original draft guidance document responds to questions about the definition of a medical food, its labeling, uses, and marketing and updates some of the existing FDA responses. The revised draft guidance confirms that all medical foods are subject to general regulations such as those for food production, food ingredients, labeling (except that medical foods are exempt from health claim and nutrient content claim requirements under the Nutrition Labeling and Education Act of 1990), food facility registration and prior import notice. It clarifies FDA’s views concerning the distinctions between medical foods and prescription drugs, applicable ingredient requirements, and the conditions and diseases FDA considers suitable for medical food dietary management.
FDA’s guidance documents, including this draft guidance, do not establish legally enforceable responsibilities and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. However, guidance documents describe the agency’s current thinking on a topic and the direction that any enforcement actions are likely to take.
Medical Food/Rx Drug Distinctions
- Medical foods need not be made available by written or oral prescription. FDA interprets the Orphan Drug Act and FDA’s implementing regulations at 21 C.F.R. § 101.9(j) (8) to require that a medical food be consumed or administered enterally under the supervision of a physician. FDA considers this requirement to mean 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) of a physician who has determined that the medical food is necessary to the patient’s overall medical care. An oral or written prescription is not required. Note: FDA does not consider foods that are simply recommended by a physician or other health care professionals as part of an overall diet designed to reduce the risk of a disease or medical condition or as weight loss products to be medical foods.
- Medical food labeling may not bear the symbol “Rx only.” The symbol “Rx only” is not to be used in the labeling of products that are not prohibited by federal law from being dispensed without a prescription. Medical foods are not prohibited by federal law from being dispensed without a prescription. Therefore, the use of the symbol “Rx only” in the labeling of a medical food would misbrand a medical food under section 403(a)(1) of the Food, Drug, Cosmetic Act (FDCA) (21 U.S.C. § 343(a)(1)) because it would be a false statement about that product. FDA does not address whether using the term “Rx” by itself would similarly misbrand the product. However, because medical foods are required by statute to be formulated to be consumed or administered enterally under the supervision of a physician, FDA would not object to the use of language to communicate this requirement in the labeling of a medical food product that is otherwise not false or misleading (e.g., “must be used under the supervision of a physician”).
- Medical food labeling may not include National Drug Code (NDC) numbers. NDC numbers are intended for uniquely identifying drugs and should not be used in the labeling of medical foods. The presence of an NDC number on a product that is not a drug may be a false or misleading representation that misbrands the product under the FDCA. In addition, FDA considers any representation that creates an impression of official FDA approval through the use of an NDC number in labeling to be misleading. FDA has not specifically addressed whether use of a 10-digit number, whether formatted as an NDC number or not, but without the identifying letters “NDC,” would similarly misbrand the product.
Medical Food Ingredients
- Any ingredient added to a medical food should be:
- a food additive used in accordance with FDA’s food additive regulations (see 21 C.F.R. Part 172);
- a color additive used in accordance with the color additive regulations (see 21 C.F.R. Parts 73 and 74);
- a substance that is generally recognized, by qualified experts, to be safe under the conditions of its intended use (Generally Recognized As Safe (GRAS)) (see 21 C.F.R. § 170.30 and 21 U.S.C. § 321(s)); or
- (4) a substance that is authorized by a prior sanction issued by FDA (see 21 C.F.R. § 170.3(l)).
In contrast to statutory provisions that exempt dietary ingredients in dietary supplements from regulation as food additives, there is no similar provision that exempts dietary ingredients in medical foods from food additive or GRAS status.
Conditions and Diseases Suitable - or Not - for Dietary Management Through Medical Foods
- Inborn errors of metabolism (IEMs). IEMs are generally considered to be diseases or conditions that a medical food could be used to manage, for example, inherited biochemical disorders in which a specific enzyme defect interferes with the normal metabolism of protein, fat, or carbohydrate. Management may include one or a combination of the following: drug therapy, modification of the normal diet, or use of a medical food. FDA explains, that for some IEMs, “a medical food is required in addition to a specific dietary modification (e.g., reduced total protein/phenylalanine for phenylketonuria) in order to obtain adequate levels of essential nutrients which are restricted by modifying the normal diet. Medical foods become indispensable for individuals with these IEMs in order to meet the daily requirements of essential nutrients and to limit the metabolic disturbances associated with the particular IEM.” FDA provides examples of specific IEMs that medical foods could help manage:
- phenylketonuria (phenylalanine restriction)
- ornithine transcarbamylase deficiency (nonessential amino acid restriction)
- methylmalonic acidemia (isoleucine, methionine, threonine, and valine restriction)
- significant modification of fatty acids/total fat such as in very long-chain acyl-CoA dehydrogenase deficiency (long chain fatty acid restriction with an increase in medium chain fatty acid levels)
- Pregnancy. FDA does not consider pregnancy to be a disease. Nutrient requirements exist for pregnancy but as pregnancy is one of the twelve life stage groups identified by the Institute of Medicine (IOM), it is not a disease. Any IOM – developed dietary reference intakes (DRIs) apply to the healthy general population, including those who are pregnant. FDA states that while a specific individual diet alone may not supply the full amount of nutrients necessary for women who are pregnant or planning to become pregnant, generally the levels of micronutrients necessary for pregnancy can be achieved by the modification of the normal diet alone. Therefore, FDA generally would not consider a product labeled and marketed for pregnancy (rather than a specific disease or condition associated with pregnancy) to meet the regulatory criteria for a medical food.
- Type 1 and type 2 Diabetes Mellitus (DM). FDA does not consider type 1 or type 2 DM to be conditions for which a medical food could be labeled and marketed. Diet therapy is the mainstay of diabetes management and a regular diet can be modified to meet the needs of an individual affected by either type of DM, along with appropriate drug therapy if necessary. DM does not generally limit or impair the individual’s capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or require other special medically determined nutrients that cannot be obtained by the modification of the normal diet alone. See 21 C.F.R. § 101.9(j)(8)(ii). Therefore, FDA generally would not consider a product labeled and marketed for DM to meet the regulatory criteria for a medical food.
- Diseases resulting from essential nutrient deficiencies (e.g., scurvy, pellagra). FDA does not consider classical nutrient deficiency diseases to be diseases for which a medical food could be labeled and marketed. These diseases result from essential nutrient deficiencies and are typically caused by inadequate intake (e.g., famine, significant calorie restriction, eating disorders, alcoholism, diet practices/fad diets). The deficiencies, excluding any permanent physical damage, can typically be corrected once foods with these essential nutrients (or dietary supplements, if necessary) are made available and consumed.
- Conventional foods that do not ordinarily contain protein or are ordinarily low in protein. Conventional foods such as fruits, certain vegetables, fats, and sugars generally are not specially formulated to delete protein or to be significantly low in protein -- instead, they are low in protein in their natural state. A medical food must be specially formulated and processed (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 by tube. 21 C.F.R. § 101.9(j)(8) (i). Therefore, conventional foods that do not ordinarily contain protein or are ordinarily low in protein would not meet the regulatory criteria for medical foods.
To ensure consideration by FDA, comments on the draft revisions should be submitted within 60 days, or by October 13, 2013.