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This article compares the legal definitions of drugs and medical food and outlines the distinctive regulatory hurdles for medical food, in particular, the need for substantiating distinctive nutritional requirements. The authors also make recommendations on how those regulatory hurdles could be overcome with definitive regulatory guidance for both distinctive nutritional requirements (DNR) and modification of normal diet alone (MODA).
Novel nutrition therapies promise new perspectives and innovative solutions to currently unmet medical needs. However, food products, with a therapeutic target and clinical benefit in a medical condition often cannot meet the requirements of their appropriate regulatory classification 'medical food.' There are uncertainties as to how to interpret and comply with significant aspects of the legal definition of the medical food category.
The problem according to the Federal Food, Drug, and Cosmetic Act, only drug products can be presented to treat a disease or medical condition.1 In cases of ambiguity, in particular concerning a product's presentation, authorities are typically inclined to consider food products as "misbranded drugs." The only food category legally permitted to make claims on the dietary management of a disease or medical condition, but not treatment or therapy, is 'medical food.' However, the legal definition for qualifying as a medical food is more demanding than the drug definition.2, 3Table 1 compares the regulatory definitions for drug and medical food products. While the drug definition only refers to a product's or substance's action and its intended use, the medical food definition has two further dimensions that need to be substantiated 1. specific patient and disease characteristics, i.e., conditions for which distinctive nutritional requirements have been established and 2. what we have termed as a "no alternative solutions clause," meaning the nutritional requirements cannot be achieved by the modification of the normal diet alone. An analogy for this clause in the drug area would be, for example, that a drug product shown to be efficacious in the treatment of obesity would only gain authority approval if its manufacturer has ruled out that a body weight reduction in a target population cannot be achieved through diet and exercise alone. The following sections outline the difficulties in complying with the additional dimensions in the medical food definition.
"… for the dietary management of a patient …"
Distinctive nutritional requirements:
"… 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"
"… the dietary management of which cannot be achieved by the modification of the normal diet alone."
No current regulatory guidance exists on what constitutes a Distinctive Nutritional Requirement (DNR) and which evidence is needed to substantiate it. This lack of guidance can lead to a situation in which a company has a nutritional product demonstrating a therapeutic benefit in a well-controlled clinical study, but its medical food classification remains uncertain because it depends on FDA's judgement if the disease or medical condition for which the therapeutic benefit has been shown is associated with a DNR. Medical food research areas affected by this uncertainty include, for instance, inflammatory bowel diseases and Alzheimer's disease.7, 8
An algorithm has been developed and published for investigating DNRs which addresses the need to understand the role of a particular nutrient in the pathomechanism of a medical condition followed by the need for evidence that compensating for the altered concentrations of this particular nutrient results in a physiological or clinical benefit.9 The proven DNR for arginine in critically ill patients is referred to as a case study for this algorithm.10 Similar to the research in arginine DNRs, academic experts are researching specific folate requirements in neuropsychiatric disorders.11 The premise of this research is that DNRs are nutritional requirements differing from the average healthy population and that DNRs are linked to the etiology and pathomechanism of a particular condition. It is recommended that health authorities engage with researchers and manufacturers of medical food products, medical and nutrition experts to develop a regulatory guidance document on establishing DNRs.
Also, no regulatory guidance is available on how to establish that DNRs cannot be achieved by the modification of the normal diet alone (MODA). Theoretically, a diet can be almost infinitely modified to either eliminate the intake of specific micro- or macronutrients or to the other extreme, by increasing the intake of specific nutrients through taking high amounts of dietary supplements on a daily basis. While a manufacturer of a medical food can specify the reasons why it is impossible, impractical, or even unsafe for patients to meet their DNRs through a modified diet including fortified foods and dietary supplements, it remains uncertain if a health authority would accept those reasons.
A judgement on the ability of an individual to adhere to a specific nutritional regime is a critical consideration in the determination of whether a special diet is possible, realistic, and not unnecessarily difficult, or even unsafe, for patients.12 This is of particular importance when a medical condition is associated with severe mental or physical handicaps such as dementia, epilepsy, or dysphagia.13-16 For such patients, providing specific nutrients suitable for their medical condition in the form of a medical food - as opposed to recommending a modification of their normal diet alone - may be a medical necessity.17 It is important to acknowledge and address these ethical and practical considerations in a regulatory guidance document to be used as a reference for manufacturers assessing the MODA question. It is recommended that health authorities engage with developers and manufacturers of medical food products, medical and nutrition experts, as well as patient organizations, to develop such a regulatory guidance document.
In summary, manufacturers of medical foods must comply with two "distinctive" regulatory requirements unique to the medical food category: the condition for which they are intended must have Distinctive Nutritional Requirements (DNRs) and those DNRs cannot be met by a modification of the normal diet alone (MODA). The DNR requirement goes to the heart of disease research and is particularly difficult to comply with for conditions whose etiology is still under investigation. The MODA dimension is equally complex because it involves a judgement regarding to what extent patients and their caregivers are capable of modifying their diet without imposing unnecessary risks and burdens. Both requirements pose significant barriers for the development of novel medical foods and de-incentivizes advances in nutritional and medical science. Regulators should develop guidance documents on DNR and MODA which are both true to science and the medical food regulations, but do so without imposing unnecessary barriers for nutritional products. These efforts would encourage and accelerate innovation in the development of safe, clinically effective medical food solutions for disease management.18
Josy Giordano-Schaefer, PhD is global regulatory affairs manager at Nestle Health Science in Epalinges, Switzerland with 12 years of experience in regulatory affairs. She may be contacted at Josy.Giordano@nestle.com.
Manfred Ruthsatz, PhD, RPh, DABT, RAC, FRAPS, is the global head regulatory advocacy at Nestlé Health Science, Epalinges, Switzerland. His healthcare regulatory experience, rounded out by quality, safety, vigilance, health economics and reimbursement, spans more than 25 years in diverse healthcare industry settings, US FDA's CDER and NIH. His publishing and speaking activities in Europe, US, Asia and Latin America include a wide array of regulatory and policy related healthcare topics with a focus on the health and disease continuum, global convergence. He may be contacted at email@example.com.
Heinrich Schneider,MD is head of global regulatory affairs at Nestle Health Science in Epalinges, Switzerland with 30 years of experience in regulatory and medical affairs, clinical research and product safety. He can be contacted at Heinrich.Schneider@nestle.com.
Disclaimer: this article reflects the personal opinion and experience of the authors. It should not be construed as an official position by any organization with which the authors are affiliated. It underlines the importance to expeditiously work on and create an environment to engage with all vested parties to help investing into sustainable solutions in healthcare, including nutrition, considering the pace demographics and diversity based needs in our environments are shifting.
Cite as: Giordano-Schaefer, J., Ruthsatz, M. and Schneider, H. "Distinctive Regulatory Barriers for the Development of Medical Foods." Regulatory Focus. October 2017. Regulatory Affairs Professionals Society.
Tags: Medical Food