Medical Foods Governance A Slippery Proposition

April 1, 2019 - 10 minutes read

A precise characterization of the regulatory category “medical foods” remains elusive to many because it represents a category that is “neither fish nor fowl”. That is, medical foods are not drugs (although they once were), nor are medical foods necessarily, a nutritionally adequate food for the general population. The difficulty in adequately describing this category and that the catergory is exempt from certain requirements for other foods, could have led to a number of abuses.  For example, the Nutrition Labeling and Education Act exempted medical foods from (1) nutrition labeling, (2) pre-market approval of efficacy claims and, (3) nutrient content claim requirements applicable to conventional foods.  As a result, this category was once contemplated by some as a means to add dietary supplements ingredients to foods because supplements were ordinarily prohibited for addition to food by the Dietary Supplement Health and Education Act nor did many dietary supplement ingredients meet the court’s definition of a food ingredient, by contributing “taste, aroma or nutritive [or technical] effect” to food. Further, because the “books were closed” by the 1970’s on what was considered a nutrient, this left an opening for manufacturers to respond to a public that wanted “something extra” in their food to support continued vitality. Therefore, the medical foods category was becoming a conduit to supplement nutritionally adequate diets, rather than provide specialized nutritional support for medical conditions based on a metabolic disorder or pathological condition.  In response, and in order to provide clarity to what was meant by the term “medical foods”, in 2016, FDA issued “FAQs About Medical Foods” (2nd edition), but in doing so, made some unjustified leaps in interpretation of the Orphan Drugs Act and set up the medical foods category for many future disputes.

The medical foods saga was initiated with the approval of Lofenolac® as a drug, to replace milk in the diets of infants with phenylketonuria – an inborn error of metabolism (IEM) characterized by a decreased metabolism of the amino acid phenylalanine, which may be expressed as intellectual impairment, seizures and mental disorders.  In an unrelated move, FDA created the category “Food for Special Dietary Use” (FSDU) (21CFR§125; later to become 21CFR§105.3), meant for accommodating particular dietary needs which exist by reason of age or physical, or pathological or other conditions, including but not limited to disease, convalescence, pregnancy, lactation, allergic hypersensitivity, etc. Because of the inconvenience and burdensome nature to consumers of Lofenolac® as a drug and because phenylketonuria would seem to fit the FSDU criteria, Lofenolac® was moved to the FSDU category. As a food, Lofenolac® was more easily obtainable by the parents of affected children.

In 1988, the Orphan Drugs Act was passed – this Act was a humanitarian initiative by Congress to confer certain economic advantages (including grants) to researchers to develop drugs, devices and foods for victims of rare diseases/conditions whose numbers are too small to make development of a drug, device or food financially viable. According to the Act:

“The term ‘rare disease or condition’ means … in the case of a medical food, any disease or condition that occurs so infrequently in the United States that there is no reasonable expectation that a medical food for such disease or condition will be developed without [financial] assistance under subsection (a) of this section.” “The term ‘medical food’ means 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.”

So far, so good. However, the FDA, in its interpretation of the law for the regulation 21CFR101.9(j)(8)(i-v), the FDA added some clarifications; that is, a medical food can be such only if the following conditions are met (Figure 2):

Therefore, it could not be clearer that a medical food must be formulated or processed to meet a certain metabolic need that cannot be addressed by simple physical modification of a conventional food (e.g., by pureeing or liquefying a conventional food); although #ii would seem to leave the door open liquification of a diet needed to feed patients with esophageal atresia (narrowing of the esophagus) or aphasia (inability to swallow), however these criteria are addressed in #i “partial or exclusive feeding of a patient by means of oral intake or enteral feeding by tube”. Also, according to #ii, with the phrase “limited or impaired capacity to ingest [e.g., atresia, above], digest…or metabolized ordinary foodstuffs…” would include something such as an enzymatic degradation of a conventional food for those patients possessing an inadequate capacity for digestion of a particular food constituent. The third dictate (#iii) reinforces the need for a modification of the nutrient support for an individual through management of a unique nutrient requirement resulting from a specific disease or condition, but it is possible such a disease or condition could have been acquired and not necessarily an IEM. The last three numbers (#iii, #iv and #v), reinforce the requirement that the medical food be used under the care and management of a physician, but would this include a naturopathic physicians?

Critically, a medical food may also be a diet bereft of some ingredient which may be essential for others; however, addition of substance to a conventional diet would not necessarily make the diet a medical food (e.g., Lorenzo’s Oil – a combination of oleic and erucic acid to slow the progression of adrenoleukodystropy, which is fed in addition to a controlled diet).

So what does meet the criteria of a medical food? Some examples as to what sort of conditions constitute a need for a medical food are presented in the following figure (Table 1).

The philosophy illustrated here (i.e., why some conditions are medical food eligible and others are not), is presumably that the first six conditions cannot be addressed by a simple change in diet, while the remaining three (i.e., lactose intolerance, gluten intolerance and diabetes) can be addressed through avoidance or, in the case of diabetes, can also be ameliorated through any number of drugs (notably, insulin), while the first six cannot be addressed by any drug available today.

On the basis of the regulatory philosophy illustrated in Table 2, the FDA has issued warning letters to companies marketing products for various conditions where the FDA does not agree with the claims of the manufacturers – even though the claim does not require pre-market approval as per the NLEA. It would seem that it would be the responsibility of the FDA to prove these medical foods do not provide the alleged benefit (Table 2). However, perhaps in an effort to avoid having to demonstrate these medical foods do not provide the alleged benefit, many of these warning letters included a statement that the substance/diet was an “unapproved drug” (Table 3), which may result in the ingredient forever being precluded from the market for non-drug purposes (as per the FDA Amendment Act of 2007).

The number of products taken off the market are a warning to producers of medical foods – that the playing field is littered with potential obstacles (Table 4). It is certainly possible with FDA’s interpretation of the statute and borrowing from other provisions in the Federal Food and Drug Act, as well as guidelines and unofficial FAQ’s, a promising substance could be forever removed from eligibility as a medical food candidate, as per the FDA Amendment Act of 2007.

Planning for the development of a medical food (or medical food ingredient) is critical and, because Burdock Group has a long-term understanding and experience of the medical foods category, we are your go-to consulting group for your next medical food project.

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