Medical Foods: Between a Rock and a Hard Place

Not a drug, but administered under medical supervision; not a fortified food, but containing added ingredients to make a food healthier. Medical foods lie somewhere in between. FDA regulation of medical foods also lies between the stricter rules for drugs and the more lenient (yet still rigorous) guidelines for dietary supplements.

The concept of a "medical food" is a relatively recent one. Products now regarded as medical foods were regulated as drugs by FDA until 1972, when the agency issued an advance notice of proposed rulemaking (ANPR), which it has since withdrawn. In 1988, Congress established the legal category of medical foods in the Orphan Drug Amendment, which states medical foods are those designed to be orally consumed, administered under the supervision of a physician, specially formulated and processed (i.e., not naturally occurring), and intended for the specific dietary management of a disease or condition that has distinctive nutritional requirements. That definition was subsequently incorporated into the Nutrition Labeling and Education Act of 1990 (NLEA), where Congress exempted medical foods from the nutrition labeling, health claim and nutrient disclosure requirements applied to most other foods.

According to FDA, medical foods are 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. Further, in the Compliance Program, FDA asserts a medical food must be primarily, but not exclusively, sold to hospitals, clinics and other medical facilities.

Deanna Minich, Ph.D., FACN, CNS, Metagenics vice president of R&D communications, further explained, Theyre intended to support specific conditions and contain combinations of macro- and micronutrients in ratios that have known biochemical rationale and are effective in nutritionally managing a disease state.

Those who suffer from certain aliments may experience inadequate ingestion of nutrients, malabsorption, impaired metabolism, loss of nutrients due to diarrhea, increased nutritional turnover inherent in certain diseases or inadequate ingestion due to a drug therapy. Medical foods can offer these patients a therapy to use with or without prescription drugs and lifestyle changes. For instance, pancreatic insufficiency is associated with reduced enzyme production; renal insufficiency drives patients to minimize uremic toxicity by following a low-protein diet and reducing phosphorus intake; Alzheimers patients can benefit from medium-chain triglycerides (MCTs) that produce ketones, offering alternative energy sources for brain cells depression can deplete folate levels; those with bone disease could benefit from additional vitamin D and calcium; and short-bowel syndrome requires nutrients that can be absorbed elsewhere in the body. All of these conditions and more can be addressed by specifically formulating foods with additional healthful ingredients.

Medical foods, unlike dietary supplements, are required to undergo pre-market scientific testing (results need to be based on recognized scientific principles, but not necessarily from clinical trials); but, like supplements, do not require pre-market FDA approval. Whereas medical foods are formulated for specific disease populations, supplements are intended for healthy adults. Medical foods cannot make therapeutic claims for treating, preventing or mitigating specific diseases like drugs can; but, they can go beyond the structure/function claims of supplements to make medical claims for dietary management of a specific disease. Also, like drugs, patients private insurance companies often cover some of the costs of medical foods. They are also covered under the Workers Compensation Insurance plans and Medicare Part D.

All ingredients of medical foods must also be GRAS (generally recognized as safe) or approved food additives. While many more fortified-food ingredients have achieved GRAS status, it is not required for those products. A medical food by definition must contain GRAS ingredients, and this status is not given easily and widely to all so-called natural ingredients, said Pierre Lemieux, COO, Acasti Pharma Inc., a subsidiary of Neptune Technologies & Bioressources Inc. Ingredients have to go through a thorough process in which all the intended uses and dosages have to be defined and presented, and backed up with appropriate safety and toxicology data.

For GRAS status, an ingredient must have technical evidence of safety that is accepted by qualified experts. FDA states, the minds of competent scientists must have reasonable certainty that the substance is not harmful under its intended conditions of use. In addition, the safety data must be generally available.

Even with FDAs seemingly distinct guidelines between supplements, drugs and medical foods, meeting the requirements for medical food can be difficult because the definition can be interpreted a number of different ways, according to Mike Bush, Ganedens vice president of business development. FDAs actions in this area may even turn some manufacturers away from this market. There are strict guidelines on medical foods, Bush said. Because of the tight regulations, more manufacturers are changing product status from medical foods to supplements or functional foods and beverages.

To ensure a medical food passes legal muster,  the marketer must demonstrate that the target patient population has distinctive nutritional requirements. An August 2010 paper from the law offices of Hyman, Phelps and McNamara stated: It is essential, therefore, that a manufacturer be able to demonstrate the unique nutritional need that results from the disease, and the fact that the product is specially formulated to meet that need. Further, the paper noted, It is also very important, in any discussion of these requirements in labeling or elsewhere, to avoid drawing attention to any possible similarity in action or effect between the medical food and any approved drug for the disease. Emphasis should be placed on food status and on the digestion/metabolism aspect of the disease.

Sticking to the regulations is crucial in the medical-foods arena, as FDA appears to have no qualms about correcting rule breakers. FDA has communicated concern over the accuracy and validity of claims and product safety of medical foods, as they are intended for use by vulnerable populations, Minich noted. More recently, FDA has stated it will review the medical food category; perhaps this additional guidance will result in the category being modified. In the meantime, the best approach to ensuring the future of the medical-food category is to develop products that are accurately labeled and clinically demonstrated to truly serve the needs of their target population. A company entering this market must make sure it has well-staffed R&D, quality control (QC) and regulatory departments to develop, test and support their products.

While regulation may be stringent, it has been relatively static, according to Sandy Bigelow, principal, Vanguard Global Associates. Therefore, industry can still safely follow the 1977 operating standard for medical foods outlined in the ANPR. FDA regulation of medical foods in the United States has reached a point of stasis as compliance issues for particular products in the marketplace have been handled through the normal enforcement processes, she said.

Lemieux also noted the unchanging nature of FDAs regulation, but added FDA may be getting more active. The regulation in the United States has been the same since 1988, and will not change soon, meaning that medical food will remain as a classification. FDA and FTC are, however, a bit more cautious, as translated in warning letters.

Indeed, warning letters are increasing, and Lemieux said FDA is generally targeting labeling and use of testimonials in its citations. With little regulatory action in the 1990s, FDA has sent at least six warning letters since 2003. In these letters, FDA charges certain companies misbranded products labeled as medical foods because they bore claims relating to diseases and conditions that lacked distinct nutritional requirements, and that the products had no unique impact on the disease. Thus, FDA concluded the products were unapproved drugs. In one 2009 letter, FDA claimed one medical-food product did not meet the definition because the nutrient requirements for the intended population could be met through modification of a normal diet, making the product unnecessary.

Another sticky situation in the medical-foods category is where to market the products. Medical foods must be labeled for use under medical supervision, and this statement must be placed prominently on packaging. However, this does not mean a prescription is required to obtain a medical food. These products can be sold over-the-counter (OTC) in food and drug stores, or as prescription products in medical clinics. Historically, a medical-food manufacturer will choose one marketing outlet and stick to it. Metagenics and PamLab, for instance, both market their medical-food products exclusively through health-care providers and pharmacies.

Dave Kronlage, vice president, marketing, PamLab LLC, noted distributing its products through the pharmaceutical distribution chains requires a prescription and is more stringent than the medical-food regulations. Another challenge in using this channel is pharmacists who use certain compendiums, such as First Database, Medispan and Gold Standard, to recommend a cheaper, generic brand to patients, which may not be pharmaceutically or biologically equivalent to a prescribed medical food. Drug databases do not verify quality or confirm the actual content of generic pharmaceutical products, Kronlage said, adding, We have evidence that demonstrates several specific generic medical foods are not safe or effective. Quality generic pharmaceuticals benefit patients, but there is no room for generics that include adulterated or unverified ingredients. Patients who take unverified generics, which contain adulterated ingredients, are being put at risk. An adulterated fake generic product can be substituted for a prescribed-brand medical food without the patient or prescribing physician knowing about it.

Receiving an ineffective, or even adulterated, medical food can be a serious health hazard, as medical-food consumers rely on them to address their decreased nutrition status. For instance, GanedenBC30®, the brand name of Ganeden Biotechs patented probiotic strain of Bacillus coagulans GBI-30, 6086, is used in medical foods, functional foods and dietary supplements for its immune and digestive health benefits. A 2009 study showed it increases the body's immune response to viruses that cause common viral respiratory tract infections, such as colds and the flu (Postgrad Med. 2009 Mar;121(2):114-8); later that year, a clinical study published in BMC Gastroenterology  (2009 Nov 18;9:85) found GanedenBC30 was significantly more effective than placebo in providing relief to subjects suffering from intestinal gas.

Bigelow noted VGA is currently helping companies develop or commercialize medical foods for diabetes; metabolic syndrome; obesity; erectile dysfunction; and specialty areas, such as tinnitis (ringing of the ears). She added the market is trending toward obesity and weight-management foods, especially for individuals with more than one disease.

Metagenics has also researched and developed several medical foods to nutritionally manage these types of conditions, including type-2 diabetes, metabolic syndrome, inflammatory bowel disease and others. Many of its offerings incorporate UltraMeal® PLUS 360, reduced iso-alpha acids (RIAA) from hops and an extract from an acacia plant. These ingredients have been shown, through extensive laboratory and clinical testing, to beneficially influence insulin activityan important factor in many prevalent health conditionsby modifying kinase activity and cellular processes that support healthy body systems, Minich said, adding UltraMeal PLUS 360 was recently part of the intervention in a multi-center clinical trial on metabolic syndrome. Publication of this research is pending, but preliminary results indicate UltraMeal PLUS 360 in combination with a Mediterranean-style, low-glycemic-load diet was effective in improving key cardiovascular risk factors in adults with metabolic syndrome.

Acasti Pharmas Onemia is also intended for patients with metabolic disorders, but specifically for those who have a phospholipid omega-3 deficiency. According to the company, Onemia can help patients who suffer from hyperlipidemia, atherosclerosis, diabetes, rheumatoid arthritis (RA) and gastroenterology disorders.

Metanx® tablets, offered by PamLab and made with 3 mg L-methylfolate, 2 mg methylcobalamin and 35 mg pyridoxal 5phosphate, are formulated for the distinct nutritional requirements of diabetic patients with peripheral neuropathy and endothelial dysfunction with particular emphasis for those individuals who have or are at risk for loss of protective sensation, lower extremity ulceration or hyperhomocysteinemia. PamLabs NeevoDHA® (including 1 mg L-methylfolate and 2 mg methylcobolamin) aids women with impaired metabolic processes due to hyperhomocysteinemia during pregnancy, high-risk recurrent pregnancy loss, impaired folic-acid absorption, impaired metabolism due to 677C-T mutations in the methylenetetrahydrofolate reductase gene and dysfunctional folic acid metabolism.

PamLab also offers ingredients for brain-health medical foods, including L-methylfolate (6(S)5-methyltetrahydrofolate), the biologically active form of folate; Deplin® 7.5mg/15mg (L-methylfolate) for those who have suboptimal L-methylfolate levels in the cerebrospinal fluid, plasma and/or red blood cells, and have major depressive disorder (MDD) or schizophrenia; and CerefolinNAC® (6 mg L-methylfolate, 2 mg methylcobalamin, 600 mg N-acetylcysteine) for individuals under treatment for early memory loss with particular emphasis on those individuals diagnosed with or at risk for neurovascular oxidative stress and/or hyperhomocysteinemia, mild to moderate cognitive impairment, vascular dementia or Alzheimers disease.

Those who consume medical foods may do so for a variety of reasons; one may be to reduce the number of pharmaceutical drugs they take. If consumers follow this line of thinking (and the same trends most consumers desire), it may lead them to want medical foods from natural sources instead of synthetic, processed ingredients. The natural-foods category has always been of interest to product manufacturers because consumers are becoming more health conscious as to what ingredients go into their foods, Bush said. It makes sense that medical-food ingredients would also take an interest in natural ingredients.

Biglow added, There is a groundswell of consumer interest for natural food products (products that do not contain artificial ingredients), and this interest could naturally be extended into the medical-foods area.

Kronlage said natural options for medicinal purposes are growing for several reasons: many times [they] equate to better safety and tolerability profile, [they] may be able to address inborn errors of metabolism better than a synthetic option, many clinical conditions are associated with a nutritional deficiency that may not be able to be corrected by a normal diet, and addressing a disease with a natural product may mean the underlying disease could be corrected or modified instead of masking symptoms with a synthetic drug.

While many consumers are more aware of natural options, the same isnt true for medical foods. In a 2009 white paper from Frost & Sullivan, The Promise of Medical Foods, the global research organization noted general awareness of medical foods, even in the medical community, is low. This may be due to a dearth of clinical studies or because physicians are often skeptical of new fields. Unfortunately, as Kronlage noted, a big struggle in this market is many health-care providers and patients dont consider medical foods a legitimate treatment option.

Confusion about the differences between medical foods and dietary supplements can also hamper market growth. According to Frost & Sullivans white paper, This can be overcome through increased dissemination of information to medical practitioners that outlines the distinguishing features of medical foods, such as their scientific basis, clinical efficacy as well as the statutory definition of this category and FDA regulation authorizing the use of medical foods for the dietary management of disease. The real challenge to the use of medical foods is in encouraging physicians to consider the nutritional status of patients, and enhance their understanding of the altered nutrient requirements inherent in disease states.

Marketing to health-care providers has helped Acasti Pharma in its efforts to increase awareness. The challenge is still to penetrate the market and reach the GPs, HCPs, N.D.s and nurses, Lemieux said. The challenge remains of conveying the message properly with good and sound science backing the efficacy of the medical food. Safety is usually easy to demonstrate, but efficacy is still a question raised by physicians who are used to prescribing Rx with a great deal of clinical support. He added, Having top-notch science behind safety and efficacy is key and crucial for success.

Even with this market hurdle, Biglow said sales of medical foods have risen with changes in the U.S. population. Because of demographic changes, the medical food markets should expect substantial growth in the next 25 years, she said. The future looks bright because many ingredient companies are looking at the medical-foods market as a template for developing the substantiation for making claims for the larger, broader fortified food markets.

Lemieux agreed growth will continue in this market, and said pharmaceutical companies and smaller companies will start to offer more medical foods as sales increase. But right now, he said, There is a void for medical foods that can be occupied and expanded if the marketing and product launch is well done.

With a hole in the growing medical-foods market, product manufacturers are sure to focus more attention on this alternative to prescription pills and capsules. Regulation issues are sure to be addressed in the near future as more consumers look for medicinal alternatives. With emerging science and clinical studies, health-care providers will also more likely see medical foods as viable options to prescription drugs and dietary supplements. Someday soon, medicals foods may not just lie somewhere in between, but be a well-known third option for health care.

Editors Note: INSIDERs Market Insight section is designed to give a broad overview of marketing and sales trends in a particular category.