Neither Food Nor Drug: Is It Time for a Third Regulatory Category?

WASHINGTON, DC—Representatives of the herbal supplement industry, federal regulators, and leaders in medical academia took tentative first steps toward the creation of a third regulatory category that would recognize botanicals and other supplements as something distinct from foods or drugs.

Approximately 250 individuals gathered for the first National Center for Complementary and Alternative Medicine (NCCAM)—Industry Colloquium, entitled, “Exploring Opportunities for Collaboration with Industry.” The day-long conference opened a dialog between the NIH/NCCAM and the botanical industry which will, hopefully, lead to more rational guidelines for herbal supplement regulation.

But the road ahead is laden with intellectual paradoxes akin to the sort posed by Rene Magritte in his famous painting, “Ceci n’est pas une pipe.” The image or definition of something and the thing that is being defined may be quite different. Before the government can develop new regulatory processes, regulators and manufacturers must first define what makes something a food or a drug, and then determine the characteristics of a third category.

And that proves surprisingly tricky.

Claims Make the Mandate

Under the 1994 Dietary Supplement Health Education Act (DSHEA), “you are what you claim,” said Freddie Ann Hoffman, MD, senior director of medical/clinical development for Pfizer, Morris Plains, NJ. And what you claim to be has a lot to do with how you are used. The complication is simply that the same plant product can be used in many different ways.

For example, garlic could be a food if you put it on pizza, a food additive when added as a powder, a drug when used for cholesterol control, or a device if inserted into the ear to prevent swimmer’s ear, said Dr. Hoffman. And then what happens if you extract components from the garlic and bottle that as a distinct product?

Scott Bass, of the law firm Sidley, Austin, Brown and Wood, of Washington, DC, explained that DSHEA determines how something must be regulated based on the “intention” of use. The current regulatory framework recognizes the following different types of claims:

  • Drug claims: for controlled substances prescribed by healthcare professionals and used to treat a specific disease state. 
  • Over-the-Counter Drug or Supplement claims: for products generally considered safe and with documented efficacy in treatment of minor ailments or physiologic states. 
  • Medicinal Food claims: used in the marketing of specialty food items to meet specific dietary needs. 
  • Structure/Function claims: widely used by the supplement industry for products that have documented mechanisms by which they affect a particular physical structure or bodily function. Structure/Function claims can posit “well-being,” but cannot state benefits in treating disease. 
  • Nutrient claims: seen most commonly with meal replacement products, and nutritional supplements such as “Ensure.” 

Each of these categories has different sets of regulations determining safety, purity and composition.

Something crosses the line between food and drug when a disease comes into the picture. If a product claims to ameliorate a disease, it is a drug; if it promotes well-being, it is a supplement—even if it is the same product.

Some industry leaders believe the laws governing claims must be changed to reflect the current state where foods, supplements, and herbs are part of a continuous spectrum of health-promoting products. Many in industry would like to see the creation of a third category for supplements. Federal regulators are at least open to considering that the current framework needs to be changed, but the government is far from making any definitive statements.

The Validation Conundrum

Throughout the conference, participants wrestled with the issue of how to document that botanicals do what their manufacturers say they do. According to James B Lassiter, MBA, President of The Lassiter Group, the “gold standard” methods used for development of prescription drugs based on single chemical constituents cannot apply when evaluating botanicals, since botanicals are usually mixtures of components. Plants contain hundreds of phytochemicals, flavinoids, polyphenols, carotenoids and other compounds.

Mr. Lassiter suggested the concept of “consistent equivalence,” which could be used for batch-to-batch variation, since herbals differ in cultivation and harvesting practices. For example, a high-performance liquid chromatograph may contain 14 peaks, any one of which is a relevant component. But the ratios between these 14 peaks can be used to compare batches and ensure standardization, even though absolute amounts of active ingredients cannot be determined.

Currently, validation testing is carried out by several competing organizations. The American Herbal Products Association, American Herbal Pharmacopoiea,, Consumer Healthcare Products Association, Good Housekeeping, and many others certify botanicals for sale to the American public. But these groups all have different standards. The public doesn’t know what they are, and cannot determine how the standards relate to safety, efficacy, potency, or purity.

In many ways, this problem has kept many allopathic physicians from whole-heartedly embracing botanical medicine in day-to-day practices. “The allopathic physician as an individual is not necessarily opposed to the use of botanicals, it is the organization of physicians which is opposed,” perhaps as a turf battle between the different approaches to patient care, according to James Cardellina., PhD, of the Council for Responsible Nutrition.

A number of medical organizations, including the American Academy of Orthopedic Surgeons, American Association of Naturopathic Physicians, American Association for Oriental Medicine, American Foundation for Urologic Diseases, American Institute for Cancer Research, and the American Osteopathic Association, had representatives at the consortium, revealing a strong and growing interest on the part of physicians groups to be involved in the regulatory process.

Some botanical industry leaders would like to see the government contribute to the standardization process by creating uniform reference standards for botanical products. These standards could be used as a gauge against which industry products could be measured.

Steven J. Dentali, PhD, senior director of botanical sciences for Nutricia USA, a global botanical and nutraceutical company, stated that because the European tradition is based on cultural experience, whole herbs or minimally processed extracts and tinctures are more acceptable. In the US, however, we tend to refine botanicals until they resemble drugs and test them as drugs, in keeping with our culture. He believes it is necessary to expand this box to include the complexity afforded by botanicals. What is needed are alternative models for the determination of components for standardization.

Alternatives to RCTs?

The third major topic under discussion was the question of how to measure efficacy. Given the complexities of herbal composition and dose, randomized controlled trials (RCTs), so beloved of the allopathic community, are expensive, complex and difficult to interpret. Small herbal trials are usually not conclusive because of statistical concerns, and large trials are too expensive to run.

Several participants advocated use of intermediate determinations of efficacy as a less expensive way to show biological activity. These less complex tests could be tissue culture tests, measurements of cytokine change, or analysis of changes using RNA microarray technology. It is thought, however, that too little is known about the relevance of, say cytokine pattern changes and disease for these intermediate tests to be immediately useful.

Conference participants did arrive at a consensus that evaluations other than RCTs must be developed as a way of demonstrating efficacy without the cost and complexity of traditional drug testing. But it seems that such tests remain a distant goal.

In general, participants felt that the National Institutes of Health should determine which tests and standards would be applicable to botanicals. The industry could be responsible for preclinical safety and efficacy, with the NIH/NCCAM carrying out later clinical trials. The NIH could form a consensus group to investigate the feasibility of such an approach.

Carole Heilman, PhD, of the National Institute of Allergy and Infectious Diseases described various legal agreements between the NIH and industry that could be used to explore herbal safety and efficacy. A mechanism like the Cooperative Research and Development Agreement (CRDA), a legal document in which each party spells out what they are responsible to achieve, could be used to reduce Federal costs, as well as benefit industry by its ability to leverage NIH research expertise.

Three clear messages emerged from this day-long conference: First, an additional classification reflecting the reality that herbal supplements are neither foods nor drugs must be created. Botanicals and other supplements would fall into this category, with standardized components, and equivalent potency. Second, some kind of uniform standardization of botanical products must be implemented to aid the public and the medical community in obtaining the maximum benefit from botanical medicine. Third, innovative methods for measuring efficacy must be developed, as the single-ingredient RCT model used for pharmaceutical research is largely infeasible for most botanicals.

Though the dialog was highly diplomatic and the words chosen very carefully, it seems that industry leaders, government officials and the research establishment are at last reaching the consensus that it is in the best interest of the public, healthcare providers, manufacturers and regulatory agencies to clarify and improve the guidelines and standards of safety and efficacy for botanical medicines.

FULL ARTICLE AND ORIGINAL SOURCE THANKS TO Holistic Primary Care and Richard Roses’s LinkedIn post:

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