In European Union legislation, a strict demarcation exists between products and ingredients that are food and those that are medicinal products. The General Food Law (Regulation (EC) No 178/2002) states that medicines cannot be sold as food and vice versa.

Of course, there are substances, especially botanical extracts and constituents isolated from botanicals, that are food plants while having pharmacological effects at certain dosages. One example is garlic, which is a ubiquitous kitchen herb and a traditional medicine for cardiovascular health. Another is cinnamon, which has been shown to influence blood sugar at certain dosages. The list goes on.

Not surprisingly, food supplement manufacturers in the EU are often confronted with the question of whether their products have a pharmacological effect, i.e. whether they are in fact medicinal products (the so-called functional medicinal products) marketed without a proper drug authorization. They usually avoid this problem by keeping the daily intake amount below the pharmacological dosage, which is defined in monographs (if the critical ingredient is a botanical, and if that botanical has a monograph).

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 “Waters become murky … considering the ‘pharmacological action’ that food ingredients are not supposed to have, has so far never been clearly defined. This means that, if there is no  monograph—as is the case for a number of plant isolates, amino acids, and other substances—there is no defined pharmacological dose. So in these cases, what kind of action is pharmacological? How should the pharmacological dose, and thus the intake amount to be avoided, be determined?”

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Unresolved Matters

So far, so good. Waters become murky though, considering the “pharmacological action” that food ingredients are not supposed to have has so far never been clearly defined. This means that, if there is no monograph—as is the case for a number of plant isolates, amino acids, and other substances—there is no defined pharmacological dose. So in these cases, what kind of action is pharmacological? How should the pharmacological dose, and thus the intake amount to be avoided, be determined?

How do legislators approach this issue? In September 2023, the German Federal Office of Consumer Protection and Food Safety (BVL) and the German Federal Institute for Drugs and Medical Devices (BfArM) issued a joint statement intending to offer clarity.

According to the medicinal products act (Directive 2001/83/EC), a medicinal product is defined as “any substance or combination of substances presented as having properties for treating or preventing disease in human beings; or any substance or combination of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.”

Legal actions, legal textbooks, and medical-pharmaceutical textbooks each have a slightly different understanding of the term “pharmacological effect.”

In pharmacology and toxicology textbooks, as well as in medical dictionaries, pharmacological action is defined, independent from the use of a substance as a drug, as “the ability of substances to interact with the human organism,” or as the science of interactions between substances and living organisms.

In summary, the medical-pharmaceutical literature defines pharmacological action as the interaction of a substance with cellular structures or endogenous substances (e.g., enzymes, etc.). It also includes interactions with the metabolism of microorganisms with the aim of eliminating them as pathogens.

The legal interpretation of a medicinal product focuses on several constituent elements:

1. It can be used in or on the human body or administered to a human being in order to
2. Through pharmacological, immunological, or metabolic action
3. Restore, correct, or influence physiological functions.

Consequently, in addition to the presence of a pharmacological effect in the medical-pharmaceutical sense, the presence of these other constituent elements must also be verified before a substance or a preparation of substances can be classified as a medicinal product.

As stated earlier, these criteria can at least in part apply to a number of typical foodstuffs, whose intake can exert a pharmacological, metabolic, and, occasionally, immunological effect. Therefore, the effect mentioned, to “restore, correct, or influence physiological function” must also apply.

However, these terms are not legally defined. However, several legal acts exist that, taken together, arrive at the following definition.

A medicinal product exists if:

• A substance or a preparation of substances
• restores, corrects, or otherwise positively influences
• human physiological functions
• in an appreciable way
• when used as intended, in a normal manner
• through targeted control from the outside, and
• the effect is scientifically proven.

Interestingly, therapeutic products are always regarded as medicinal products, even if a therapeutic effect cannot be substantiated. Thus, even if there is no known mode of action, a product can still be regarded as a functional medicinal product.

Still Ambiguous

Clearly, the joint statement does not quite solve the conundrum, nor does it remove the need for case-by-case decisions. Food business operators in the food supplement space should generally be aware of the demarcation issue as the regulatory environment becomes stricter and more products are under fire for being functional medicinal products. Experienced consultancies such as analyze & realize GmbH stand ready to assist in these matters.

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Dr. Joerg Gruenwald is co-founder of analyze & realize GmbH, a specialized business consulting company and CRO in the fields of nutraceuticals, dietary supplements, herbals and functional food, and author of the PDR for Herbal Medicines. He can be reached at analyze & realize GmbH, Waldseeweg 6, 13467 Berlin, Germany; +49-30-40008100; email: jgruenwald@a-r.com, www.analyze-realize.com