Let’s talk medical foods, shall we?

For those of you who haven’t heard of them, a medical food is a food that is created in order to be eaten or administered under the supervision of a physician for the purpose of dietary management of a disease that has distinctive nutritional needs that cannot be satisfied by regular dieting. Medical foods were defined by the FDA in the 1988 Orphan Drug Act Amendments.

Phenylketonuria (PKU) is one such disease that requires medical foods, a rare genetic condition that causes a buildup of the amino acid phenylalanine. To learn more, click here.

To understand medical foods is to also understand that they are hard to come by and not always covered because of opposition from insurance companies.

For people who suffer from PKU, the main form of treatment is dietary adjustments that include these special formulas. In fact, PKU is the sole reason why the category of medical foods even exists. They became legal the moment Ronald Reagan penned them into law during the 1988 Orphan Drug Amendments, but as the name suggests, it wasn’t meant for the treatment of PKU, but for orphans. This starting off on the wrong foot was perhaps a forshadowing of the coming

Medical Foods Can Mean the Difference Between Life and Death

What the proposed best practices omits was that access to Lofenalac dictated the difference between life and death for those touched by PKU. Those who had Lofenalac thrived. And, with continuous therapy, they could have opportunity for living a successful life. Those without this treatment were condemned to a lifetime of institutional care and mental retardation.  Permanent disability?  Brain death? There is no medical food to date that can confer a proven benefit with significant mental growth in a PKU individual who had already sustained brain damage prior to dietary intervention. PKU is the one and one reason only the category of medical foods exists as well as being the driving force for an early version of the Orphan Drug Act a decade before ever being passed in Congress!

The terms “medical foods” were not legal until the 1988 Amendment to the Orphan Drug Act, which was signed into law under the Republican Reagan administration in 1983. Why? For orphans!  There is no mention of this in proposed best practices nor any appropriate reference given to Lofenalac as the first PRESRCIPTION DRUG FDA APPROVED FOR TREATMENT OF PKU. Later generation medical foods still fall purview to the former Bureau of Foods (as did Lofenalac), which has now been renamed the Center for Safety and Applied Nutrition (CFSAN).  And, both the CFSAN and Center for Drug Evaluation and Research (CDER, former Bureau of Drugs) are not without the aforementioned controversies eloquently described by Burnett in the article.

I would agree withdrawal of 1996 Advanced Notice of Proposed Rulemaking (ANPR) in 2003 was a tragic move on the part of the agency, and the 2016 finalized guidance falls significantly short of solving anything. Medical foods should be a priority for the agency – and the time to shift attention has never been more critical now than ever.  For example, First Databank set off an alarm in assuming its “pseudo- regulatory” and “possibly illegal role” as per Burnett in today’s Era of Affordable Care Act.¹ First Databank, in acting as FDA enforcer where they have no business, caused much damage in the form of significant financial blow to industry stakeholders and patients forced out of treatment options with lost coverage on medical foods in the wake of sudden May 2015 blanket reclassification from Rx to OTC.

This spread of miscommunication by one of the nation’s largest and most respected drug databases for whom insurers (and in my case, Congressional policy makers base therapeutic decisions and reimbursement) impacted me most negatively as end consumer and subscribed member to the Federal Employee Health Benefits program.

I spent months with a pro-bono assistance team from Arnold & Porter, LLP to reverse a historical wrong on losing the first-ever prescription coverage benefit (my one and only access to treatment with medical foods) under BlueCross BlueShield carrier to the Federal Plan. And, what is the irony in all this? I am a pharmacist.

Head Buried in Sand

For the agency to be idle with its head buried in the sand is absolutely unjustifiable given the times and track record of “guidance to nonexistence” as expressed in conversation with Burnett. Even worse, is the continuing  operations of a 1970s framework in the 21^st century, and it is much unrealistic to expect the market to be viable any longer (especially for rare disease) when regulatory policy change has been outpaced by a changing science and political environment.

Burnett expressed frustration with such irresponsible governance, which even predates the Orphan Drug Act and the industry having been left to interpret federal statute and self-regulate in the years following its passage. Many subsequent attempts to advise the industry were nothing but utter failures and created more confusion throughout the years, especially following the 1990 Nutrition Labeling and Education Act (1990 Amendments) and the 1994 Dietary Supplement Health and Education Act (DSHEA) which pretty much equated to opening Pandora’s box.

As per the 1993 Federal Register, the 1990 Nutrition Labeling and Education Act incorporated the statutory definition of medical foods and allowed for exemptions on nutritional labeling, health claims and nutrient contents.⁶  Although the language was still too broad and vague, and necessitated more FDA final rules on implementing the 1990 Amendments, the clarifying criteria for what constitutes a medical food were finally provided.⁶  Similarly, passage of the DSHEA brought more confusion, with exemptions for unregulated dietary supplements and provision of allowances for structure-function claims as acceptable and no premarket approval requirements and thereby further complicating the distinguishing role and appropriate use of medical foods from nutritional supplements (similarly classified as “foods.”)

And, if the industry thinks it remains challenged by such regulatory burden and communication hazards today (certainly worthy of kick-starting discussion on new rulemaking), imagine the burden of proof on rare disease patients: few in numbers and left to fend on their own without fancy lawyers and big money commanding response to anyone and everyone who would listen about what constitutes a medical food.

Burnett hit the nail on the head in stating the patient’s worse nightmare: “Even if these products have GRAS status or efficacy studies that substantiate label claims, the lack of FDA approval adversely impacts understanding, acceptance, and utilization of MF by the wider medical community.⁷”

FDA Approval – The Holy Grail

As a pharmacist, I concur this is also a nightmare.  It is the FDA stamp of approval which is the single-most precipitating factor triggering prescription drug formulary management and therapeutic decision making.  If a firm is granted approval, (which they would seek if profitable), there is more likelihood for patient reimbursement (which translates to access for most folks); but this is not necessarily always a guarantor of coverage.

However, the FDA approval can also open up the adjudication processes within institutions and pharmacies for nonformulary approval pathways and make an exception for getting the appropriate treatment into the patient’s hands and meeting disease-specific needs.

A unique identifier for medical foods as a drug (but without tighter regulation) under conditions of safe use that assure payers, prescribers, providers, consumers and stakeholders alike the medical food is safe, legitimate, beneficial, substantiated with evidence for claims (not to mention cost effective) would be a step forward in the right direction.  This concept is not new to the agency for exploring innovating access solutions and invokes what is known as dual availability.

Furthermore, application of this concept to medical foods challenges current FDA framework with flexibility in design, rethinks the terms “misbranding” as it pertains to pharmaceutical labeling, and is explored further in my 100+ page strategic capstone report calling for adoption of an FDA exceptional labeling standard that is long, long overdue in mitigating the biggest market failure posed to the industry: miscommunication. (See endnote.)

If the industry is still screaming about the division in the agency between the CDER and CFSAN (where the food and drug properties are clearly split just as they were prior to 1972) resulting in “millions of dollars in delay and negotiation costs with IRBs) today,¹  imagine the toll on the small, orphan innovators who are more constrained with leveraging high costs on low volume products for patients with legitimate need and rare disease AND WHO HAVE NO OTHER OPTIONS!  I will get out my violin for this trade association and would like to welcome them to PKU life in dealing with a chronology of damage that stems from 1972.

It behooves the NMFC to find some common ground with rare disease and level the playing field if there is genuine concern about who is most severely impacted by the alter egos of the US Congress and the FDA on a shared framework and practices surrounding medical foods.  It is one thing to propose to Congress giving the CFSAN authority for review or approval pathway as per Burnett.  It is another for Congress to actually give FDA the resources and mechanisms to do their job as was called for back in the 1960s with implementation of DESI, the Drug Efficacy Study Implementation project.

Medical Foods Debacle

Nobody will own up to what has been coined the “medical foods debacle⁸?” I concur with the coalition and think the CFSAN and CDER need to stop the division and damaging behavior, if this is ongoing internally with the agency – it plays out very bad in policy outside FDA walls. Furthermore, how about engaging the Office of Orphan Products Development on finding responsive regulation? It is unfortunate for the PKU community to have languished for so long in this gray category and be slighted a voice among an expert panel called for by the coalition’s proposed best practices and  in revisiting the language of the ANPR.  The problems are known, do we really have to keep rehashing them?

Patients Need a Seat at the Table