Medical Foods

By 2030, nearly 20% of the U.S. population will be older than 65, according to the Federal Interagency Forum on Aging-Related Statistics (Washington, DC). Because many of those Americans will be in poor health, some manufacturers are excited about the prospect of medical foods, a regulatory category that has received scant attention from FDA until fairly recently.

What are medical foods? FDA has a very specific definition, found in section 5 (b) of the Orphan Drug Act. The act states that a medical food is: 

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.

 Before 1972, FDA treated medical foods as orphan drugs intended for very small populations. Since then, the nature of medical foods has changed and the number of medical foods has expanded. Some products use the latest nutrition science to help address special dietary needs. But other products currently positioned as medical foods may not meet FDA's statutory definition.

FDA issued new guidance documents in May 2007 to clarify what is and isn't a medical food. The documents underscore the fact that the agency considers "the statutory definition of medical foods to narrowly constrain the types of products that fit within this category."

Companies marketing medical foods that fall short of that definition can expect to receive a knock on the door, or at least a certified letter in the mail (return receipt requested), from FDA. Highlighting its interest in the category, the agency has already sent warning letters to several manufacturers in the past 12 months.

Medical Foods Target a Wide Range of Health Conditions

RESEARCHERS STILL HAVE A LOT TO LEARN ABOUT THE RELATIONSHIP between diet and disease. But that hasn't stopped medical food manufacturers from using the latest science to help people coping with illness address their nutritional needs. Over the last few years, a growing number of medical foods have become available. While many medical foods are fairly straightforward, some illustrate how confusing the distinctions between medical foods, drugs, and supplements can be. A small sample is described below.

Fosteum is intended for the clinical dietary management of the metabolic processes related to osteoporosis and osteopenia, according to its manufacturer, Primus Pharmaceuticals Inc. (Scottsdale, AZ). The medical food contains many ingredients known to dietary supplement manufacturers, including the isoflavone genistein; vitamin D; and the chelated mineral zinc chelazome, a bioavailable form of zinc supplied by Albion Laboratories Inc. (Clearfield, UT). Fosteum is actually available in capsule form, using Vcaps vegetarian capsules from Capsugel (Peapack, NJ).

The manufacturer's Web site describes Fosteum as "a specially formulated prescription medical food, developed from natural ingredients, that is used for the clinical dietary management of osteopenia and osteoporosis. Fosteum is indicated when a good diet and supplements like calcium plus vitamin D are not enough, but you are not ready for drugs with their potential for side effects."

Limbrel, another medical food product from Primus, is described as "the first prescription product developed and formulated specifically to safely meet the distinctive nutritional requirements of patients with osteoarthritis through dual inhibition of arachidonic acid metabolization and antioxidant action rather than selective COX-2 inhibition." Limbrel contains a proprietary blend of flavonoids, including baicalin and catechin.

Glucerna is a line of products designed to help people with diabetes control their blood sugar levels. The line, which consists of shakes, bars, and cereals, is manufactured by Abbott Nutrition (Columbus, OH). Glucerna's ingredients include chromium picolinate; phytosterols; and Enova diacylglycerol oil, a digestible oil developed by ADM Kao LLC (Decatur, IL) that passes less fat into the bloodstream and lowers serum triglyceride levels. Glucerna shakes won a ChefsBest (San Francisco) best taste award in 2008. Consumers can buy the items at food, drug, and mass retailers, but Abbott notes on its packaging and marketing materials that "Glucerna products are for use under medical supervision as part of a diabetes management plan."

Boost Glucose Control, a competing product from Nestlé Nutrition (Vevey, Switzerland), contains more protein but less sugar than Glucerna. The product, a spin-off from Nestlé's Boost line of nutritional energy drinks, also contains the amino acid L-arginine. According to Nestlé, Boost Glucose Control is "a great-tasting healthy snack specifically formulated for people with diabetes that has been clinically shown to help manage blood glucose levels." Nestlé's tag line for the product also includes the phrase: "Great for people with diabetes."

Several Explicit Requirements

FDA's 2007 guidance lists at least three explicit requirements for medical foods: 

• The product must be a food for oral or enteral tube feeding.

• The product must be labeled for the dietary management of a specific medical disorder, disease, or condition for which there are specific nutritional requirements.

• The product must be used under medical supervision.  

Medical foods are also subject to other food manufacturing regulations, including: 

• Good manufacturing practices (GMPs) for foods.

• Registration of food facilities.

• Low-acid canned food regulations and emergency permit control regulations, if applicable.

• Labeling regulations, including statements of identity and contents, lists of potential allergens, and disclosure of the manufacturer's name and place of business.  

One notable difference between drugs and medical foods is the absence of a premarket approval requirement. According to FDA, "medical foods do not have to undergo premarket review or approval" and "individual medical food products do not have to be registered" with the agency.

On the other hand, as with other kinds of foods, medical foods must use ingredients that are either generally recognized as safe (GRAS) or approved food additives. Thus, while drugs, dietary supplements, functional foods, and medical foods have several similarities and differences, there are distinct, and in some cases overlapping, regulatory requirements for each.

How do these regulatory distinctions work in the real world?
As an example, the drug Fosamax treats or prevents osteoporosis; the supplement calcium helps maintain strong bones; and the medical food Fosteum helps manage metabolic processes linked to osteo­porosis. Merck's (Whitehouse Station, NJ) Fosamax and Primus Pharmaceuticals Inc.'s (Scottsdale, AZ) Fosteum both require prescriptions; calcium does not.

If you're still confused about the differences between drugs, supplements, and medical foods, one way to define medical foods is to consider what they are not. Medical foods are not intended for use by healthy people. They are not designed for self-treatment. They are not natural or conventional foods. And they are not simply conventional foods with health claims, according to FDA.

Rather, medical foods are intended for people with specific, and often chronic, health conditions. They should be used under a doctor's supervision. They must be processed or specially formulated to meet explicit nutritional needs. And they don't make the same kinds of claims as drugs or supplements.

In addition, because they are not designed for use by the general population, medical foods are usually, but not always, found in doctor's offices, hospitals, pharmacies, and other healthcare facilities, rather than in mass retail outlets.

Taking Compliance Seriously

Because they don't require premarket review, medical foods can be an attractive product for manufacturers. However, medical foods still have regulatory requirements, and there are risks for noncompliance. FDA considers adulterated, misbranded, or contaminated medical foods to be especially hazardous. The agency therefore developed a compliance plan for medical foods that involves a combination of inspections, surveillance, and enforcement activities.

In 2007, FDA sent out several warning letters to medical food manufacturers that shed some light on its concerns. The agency seems to be paying special attention to both the intended use and composition of products marketed as medical foods.

For instance, in a September 28, 2007, warning letter to Efficas Inc. (Boulder, CO), FDA claimed that one of the company's products for allergies and asthma did not meet the definition of a medical food because "although asthma and allergies are diseases, neither has distinct nutritional requirements that are based on recognized scientific principles and established by medical evaluation." In the letter, FDA also objected to some of the product's claims and labeling.

Moreover, in a December 12, 2007, warning letter to the Ross Nutritionals division of Abbott Laboratories (Cleveland), FDA noted that a lab analysis found a discrepancy between the amount of vitamin K in a product and the amount listed on the label.

"Because medical foods are used for the dietary management of diseases and conditions with distinctive nutritional requirements, over- and underdeclaration of nutrients in medical foods are of particular concern to FDA," wrote the agency.

Medical Foods Q & A:

Q: What is the difference between a functional food and a medical food?
A: Functional foods are foods enriched with nutrients and other ingredients that possess health-promoting properties and are intended for use by the general population. Medical foods are foods that are formulated to address specific nutritional deficiencies that arise as the result of disease or injury and are intended for use by patients under a doctor's supervision.

Q: My company has a product that is clinically proven to alleviate the symptoms of a disease. Can we market it as a medical food?
A: Probably not. Medical foods are used to manage the nutritional needs of a health condition, rather than to treat its symptoms.

Q: How do the regulatory requirements for medical foods compare with the requirements for pharmaceuticals and dietary supplements?
A: Medical foods, drugs, dietary supplements, and conventional foods each have specific regulatory requirements. In general, while drugs require premarket review and approval by FDA, dietary supplements, medical foods, and conventional foods do not. However, medical and conventional foods must contain generally recognized as safe (GRAS) ingredients and approved food additives. In addition, dietary supplements are supposed to contain only ingredients that were in use before 1994 or that have been the subject of a new dietary ingredient petition. Drugs and supplements each have their own good manufacturing practices (GMPs) regulations, while medical foods and conventional foods are covered under food GMPs.

Q: How can I learn more about FDA's requirements for medical foods?
A: FDA issued guidance documents for medical foods in May 2007. The documents, as well as FDA's compliance program manual for medical foods, are available on FDA's Web site, www.fda.gov. FDA also published an advance notice of proposed rule making (ANPR) for medical foods in 1996 but withdrew the ANPR in 2004.

Why Now?

Is there a reason why FDA revisited the concept of medical foods last year? One possible explanation is that the agency wants to prevent companies from marketing products as medical foods as a way to bypass the premarket review process for drugs. Another explanation is that the agency is simply trying to get ahead of the current wave of new product launches.

According to a May 31, 2007, advisory from Covington & Burling LLP (Washington, DC), FDA's May 2007 medical foods guidance may have been sparked by "the continuing proliferation" of medical food items.

"FDA advises in the guidance that it considers the statutory definition of medical foods to narrowly constrain the types of products that fit within this category of food, but the agency is apparently not prepared at this time to provide more clarity as to the bounds of that definition. While FDA warning letters for purported medical foods have focused primarily on the absence of distinctive nutritional requirements for the disease or condition for which the product is marketed, the agency has also recently addressed unlawful marketing practices and illegal drug claims for purported medical foods," the advisory said.

Foods of the Future

FDA's decision to offer guidance last year bodes well for medical food manufacturers, but more details about FDA's definition of the category are necessary before medical foods can really flourish. As some dietary supplement and functional food manufacturers know all too well, FDA guidance that seems unclear, inconsistent, or arbitrary can create an air of uncertainty that puts a damper on enthusiasm and investment. Additional information and stepped-up enforcement activities in the near future could help clear the way for a new era of innovative new medical food products.