Here at Berkshire we love food. We love making it safer by researching it, writing about it, and ‘consumer testing’ it. From ruby chocolate to cockroach milk, charcoal ice-cream to pizzas in space, we’ve scanned the aisles and checked out the newest and tastiest trends in order to bring you the most up-to-date, cutting-edge food safety information. Likewise, we’re keen to explore the intersectionality of emerging technologies as they relate to the food industry – from 3D-printed pizzas at the ballgame to medical foods for disease management. Why? Because we know you are equally hungry for the information. Moreover, the marriage of high-tech innovation and food is one that excites us.
Our interest in emerging technologies in the food and beverage industries goes beyond current fads. It extends to reflecting on how targeted food production can be leveraged to address more substantive issues. The production of custom food items, perhaps via additive manufacturing, could present us with the opportunity to address the needs of some of the overlooked demographics of our society. For nutritionally compromised individuals, for example, whose medical conditions require specific nutrients in a regulated dosage. Or to service the needs of those increasing numbers of families living in the newly spreading food deserts, impoverished areas in which access to high-quality, fresh food is restricted. And what about the field of medical food? Could technology also be the way to bring that to those who need it most? Medical food? Wait – what’s that? Let’s take a look…
Ancient Greek physician and generally accepted ‘father of modern medicine,’ philosopher Hippocrates once entreated his students to examine their health in terms of their diet. ‘Let food be thy medicine and medicine be thy food,’ he declared, claiming a poor diet to be the root cause of many illnesses and diseases. But what Hippocrates could not have foreseen is the degree to which our modern society would take his words to heart. In addition to the efforts of individuals to improve their health through optimal nutrition, the medical establishment is also on the cusp of accepting that nutrition plays a significant role in overall wellness. And this is especially true in the case of medical foods. So what exactly are they why are they so important? Let’s look first at a working definition of what medical food is, and of what it is not.
Given that medical foods are, under the terms of the Nutrition Labeling and Education Act of 1990 (NLEA), largely exempt from certain labeling strictures relating to health and function claims, marketing nutraceutical products as medical foods is an attractive option for manufacturers. But such representation is disingenuous insofar as the definition of a medical food is surprisingly narrow. While products such as nutritional supplements and supports are intended to enhance diet and health in broad consumer populations, medical food products are engineered specifically to sustain life in critically ill or infirm populations.
Medical foods are defined and recognized based on the Orphan Drug Act (ODA) of 1983. This act – a reaction to calls for legislative change by the National Organization for Rare Disorders (NORD), a loose coalition of patients with rare diseases like Huntingtons and muscular dystrophy – promotes pharmaceutical research into drug development for rare conditions by loosening testing requirements and financially incentivizing clinical research and marketing. The idea behind the bill, sponsored by then chairman of the Energy and Commerce Subcommittee on Health, Henry Waxman, was that conditions such as Crohn’s or Hansen’s disease which are suffered by a relatively small number of patients remain without drug treatment because economically it is not viable to pursue research. With only a small patient pool, the costs of R&D and of bringing a product to market would never be recouped. By eliminating certain clinical testing requirements, costs are lowered and companies just might find it within their remit to investigate developing treatments for conditions outside of the blockbuster market.
Nor are they supplements, and this is a distinction that is imperative to understand. Although medical foods may share the same form factor as supplements – that is, they may come in capsule or pressed powder form – they are not supplements and so are not regulated in the same way. Equally, although prescribed by a physician, medical foods are equally not pharmaceutical drugs. Certainly, they may look like supplements or medications, but that’s where all similarity ends. And outward appearance can be deceptive.
Required to meet the standards that classify a product as GRAS (Generally Recognized As Safe) by the Food and Drug Administration (FDA), medical foods must also conform to certain criteria. Prescribed by a physician, they are administered orally and with close patient monitoring with the aim of providing specific dietary support for the management of a medical condition. They must meet specified nutritional criteria for that condition and their safety and efficacy must have been scientifically demonstrated and recognized. And the patient’s need for the food must have been ascertained by medical diagnosis. In fact, the definition of medical foods is governed by the Orphan Drug Act of 1983 (21 U. S. C. sec 360ee(b)(3)) which states that it 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.’(1)
But in terms of their manufacture, the products should comply with current Good Manufacturing Processes (cGMPs) associated with food designated for human consumption.
So although it would be logical to assume that medical foods, unlike supplements, are subject to FDA regulation, this is not the case. Unlike their lookalike pharmaceutical counterparts, medical foods are not regulated as drugs and are exempt from the labeling requirements regarding nutrient content and health claims to which food items are subject. In fact, per the FDA’s Code of Federal Regulations Title 21 (21 CFR), medical foods need to have only a statement of identity, a statement of net quantity, the name and place of business of the manufacturer and packager, and a list of ingredients in descending order of predominance.(2) That said, any false or misleading claim in either area would be deemed ‘misbranding’ under the terms of the Federal Food, Drug, and Cosmetic Act (FD&C Act), section 403(a)(1). But in terms of their manufacture, the products should comply with current Good Manufacturing Processes (cGMPs) associated with food designated for human consumption. These regulations govern the ways in which manufacturing equipment is maintained and sanitized, the cleaning of surfaces and utensils with which the products have direct contact, use and storage of toxic chemicals, pesticides, sanitizers, and cleaning products, the storage of single-use items, and the testing of food-packaging materials. The complete breakdown of cGMPs for food intended for human consumption is covered by 21CFR, Chapter 1, Subchapter B, Part 110 which itemizes regulations for the manufacturing, packing, and holding of human foods.(3)
Previously branded as a medical food for the treatment of cognitive impairment in Multiple Sclerosis and Alzheimer’s disease, Axona is based on a medium-chain triglyceride (caprylic triglyceride) formulated from fractionated coconut oil. In Alzheimer’s patients, it was intended to support metabolic processes and serve as an alternate fuel source for the brain. Following enzymatic breakdown in the intestine, medium-chain fatty acids from the coconut oil undergo oxidation in the liver to form ketones which then pass through the blood-brain barrier and perform as a ‘back-up’ energy resource for cells with an impaired ability to process glucose. Launched in 2009 by manufacturer Accera, Inc., a clinical development company based in Boulder, CO, that focuses on treatments for neurodegenerative diseases, Axona was evaluated in Phase II clinical trials and administered to more than 30,000 patients by 2012. However, following a media expose in 2011, organizations such as the Alzheimer’s Association and the Mayo Clinic distanced themselves from the product while the FDA also determined Axona did not meet the statutory definition of a true medical food.
And for manufacturer Primus Pharmaceuticals Inc. the situation was even more dire. In December 2017, the FDA recommended that Scottsdale, AZ-based Primus voluntarily recall their osteoarthritis treatment, Limbrel. Marketed in capsule form, Limbrel was formulated to ‘manage the metabolic processes associated with osteoarthritis’ but concerns arose when reports of drug-induced liver injuries and cases of a lung condition known as hypersensitivity pneumonitis surfaced. Of the 194 reports received, 30 cases ‘contained sufficient information to use the Council for International Organizations of Medical Sciences (CIOMS) causality assessment method to determine the likelihood of an association between the consumption of Limbrel and the adverse events reported exists.’(4) In other words, there was clear and direct evidence pointing to Limbrel as the cause of jaundice, nausea, chronic bronchitis, respiratory difficulties, and gastrointestinal problems in patients taking the product.
Interestingly, because Limbrel was marketed as a medical food but is considered by the FDA as a drug, it was not subject to mandatory FDA recall. However, in the face of growing concern, Primus issued a voluntary recall on January 26, 2018, following a series of FDA inspections which ultimately resulted in no compliance issues. At this time, the company stands firmly by its product and its designation as a medical food and also seems to have support from the medical community. Indeed, in its own press release the FDA states:
‘Physicians with extensive experience with Limbrel have provided written testimony to FDA confirming the benefits and safety of Limbrel for managing OA and to establish the medical necessity of Limbrel for elderly patients with comorbidities who cannot use NSAIDs and have a strong desire to avoid opioid use if possible. For these and other patients and their medical professionals who have stated their desire for continued access to Limbrel, Primus will seek to work with FDA to return Limbrel to the market as quickly as possible.’(5)
So, given that there is strong support among physicians for some medical food products, is there a better way to access them? As discussed, medical foods are required for a relatively small number of patients. Intended for very targeted demographics, these compounds aid in extremely narrowly focused treatments and having them always available and on-hand is a costly proposition. So could there be a better way to offer delivery to the patient?
In the age of additive manufacturing and pharmaceutical compounding, the answer could be a tentative ‘Yes.’
In previous articles where we’ve discussed the role of compounding pharmacies in the creation of highly customized therapies the focus of our research has frequently been on uncovering shady players with questionable business practices. That notwithstanding, we do acknowledge that the concept of pharmaceutical compounding is a very useful one. With everything from a morning cup of coffee to self-driving cars being increasingly tailored to the customer’s exact preferences, it’s reasonable to imagine that an Rx should also be highly customized. Human bodies are not machines and, in the same way that one size definitely does not fit all, pharmacological dosimetry should not be cookie-cutter. So could it be that a cost-effective and efficacious way of delivering these medical foods to the most vulnerable patients lies at the intersection of pharmacy compounding and additive production? Could cost and safety concerns be addressed more fully by having facilities within hospitals to custom design and ‘manufacture’ limited supplies of medical foods based on an individual patient’s requirement?
Although this clearly would not be within the budget of every medical establishment, the larger facilities that cater to the highest number of the targeted patient pool could be established as regional centers with compounding/manufacturing facilities on-site. By controlling the sourcing, production, and quality of the final product, clinicians and pharmacists would be assured of the safety of their product – one that, as we are reminded by the FDA guidelines themselves, is not mandated to meet the same requirements demanded for drugs. Perhaps this could be a path forward, or perhaps it makes more sense to expand the remit of the FDA to control and regulate the gray intersectional area where ‘food’ meets ‘medical food’, ‘supplements’ and ‘drugs’ and to bring regulations and guidelines into some kind of synchrony.
What are your thoughts? Given safety and supply concerns for medical foods, could on-site production be the answer? Let us know in the comments.