Regulatory Status
A wide range of Finished Products from food to medicines can be developed to target the microbiome
Due to the importance of the microbiome in human health, and because the understanding of health and disease has evolved and is now seen as a continuum between a healthy state towards a diseased state, a wide variety of microbiome interventions are currently being developed in order to act along this continuum.
Food products and food supplements have been at the forefront of these developments and have recently been joined by therapeutic interventions. These interventions all aim at maintaining or improving human health by targeting human microbial ecosystems: gut, skin, vaginal, lung, oral, nasal…
Microbiome science is now a vibrant field of innovation with products developed along this continuum from health to disease.
For this reason, regulatory concepts and awareness is key so all stakeholders can bear in mind the limits within which their products will be evaluated for safety, quality and efficacy, and the frameworks through which these products will reach market.
An active ingredient can be used in any number of finished products
For example, in the European Union, regulatory statuses are not mutually exclusive. A given microorganism (the active ingredient), may be used in various types of products. In order to address the regulatory requirements applicable to those finished products in terms of safety, efficacy, and quality, the microorganism itself is not really the issue. Indeed, a future product’s regulatory status is defined by the intended use of the finished product, whatever active ingredient it may contain.
Microorganisms are no exception.
A common myth within the microbiome field is that what is known for a strain can be extrapolated to all finished products containing that strain. Regulatory awareness can help to avoid erroneous thinking and optimize translational product development.
Intended Use
A key principle when determining the regulatory status of a finished product
‘Intended Use’ is a key concept in determining the regulatory status of a finished product. The FDA defines this concept as, “the objective intent of the persons legally responsible for the labeling of an article […]. The intent may be shown by such persons’ expressions, the design or composition of the article, or by the circumstances surrounding the distribution of the article. […] This objective intent may, for example, be shown by labeling claims, advertising matter, or oral or written statements by such persons or their representatives.”(21CFR201.128).
The FDA specifies that a product’s intended use(s) is of high importance, because:
- It can affect how the product will be regulated and whether it will be regulated as a drug.
- It can render the product a drug, independent of its ingredients, and regardless of whether or not one considers the product a drug.
Developers can effectively determine the intended use of their finished product(s) by answering the following questions:
- What is my product expected to do?
- How is my product expected to exert its effect?
- Who is the target population of my product?
Based on the determination of a product’s intended use, finished products will fall under the corresponding regulatory status – this regulatory status will then specify the constraints, standards, and requirements to reach market.
Appropriate regulatory status for
a product’s intended use
In the European Union, microbiome-based finished products, depending on their intended use, may fall under various regulatory statuses for which dedicated legislations lay out the standards and requirements to reach market:
Food
EU regulation 178/2002/EC defines food as:
“…any substance or product, whether processed, partially processed or unprocessed, intended to be, or reasonably expected to be ingested by humans……‘Food’ includes drink, chewing gum and any substance, including water, intentionally incorporated into the food during its manufacture, preparation or treatment.”
Foods are intended for the general population.
Food supplements
EU Directive 2002/46/EC specifies that food supplements are “…foodstuffs the purpose of which is to supplement the normal diet and which are concentrated sources of nutrients or other substances with a nutritional or physiological effect, alone or in combination, marketed in dose form…”.
Food supplements are intended for the general population.
Food for special medical purposes (FSMP)
Under Regulation 609/2013/EC Foods for special medical purposes are defined as: “food specially processed or formulated and intended for the dietary management of patients, including infants, to be used under medical supervision; it is intended for the exclusive or partial feeding of patients with a limited, impaired or disturbed capacity to take, digest, absorb, metabolize or excrete ordinary food or certain nutrients contained therein, or metabolites, or with other medically-determined nutrient requirements, whose dietary management cannot be achieved by modification of the normal diet alone”.
Foods for special medical purposes are intended for the dietary management of sensitive populations, including people affected by medical conditions, who have nutritional needs different than that of the general population.
Cosmetics
EU regulation 1223/2009/EC defines cosmetics as “ any substance or mixture intended to be placed in contact with the external parts of the human body (epidermis, hair system, nails, lips and external genital organs) or with the teeth and the mucous membranes of the oral cavity with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance, protecting them, keeping them in good condition or correcting body odors”.
Cosmetics are intended for the general population.
Medicinal products
Medicinal Products for human use are regulated by the Directive 2004/21/EC amending Directive 2001/83/EC. In this directive medicinal products are defined as:
“(a) Any substance or combination of substances presented as having properties for treating or preventing disease in human beings;
or
(b) 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.”
Medicinal products are intended to prevent or treat a disease through the restoration, correction or modification of physiological functions and targeting patients or population highly prone to a disease.
A finished product’s quality, safety and efficacy is bound by its regulatory status
Risk at the individual level, as well as at population level, might be very different based on the intended use of a product. Hence the role of competent authorities in charge of assessing products within each regulatory status is to balance the risks and benefits of each finished product at the individual and population level (within the remit of their scope/regulatory status).
For example, a certain level of risk might be acceptable for products targeting populations affected by life-threatening conditions, if they show strong efficacy; such risks would otherwise be completely unacceptable in the general population. Whereas for products which are intended to feed the general population, one can understand that no level of risk is acceptable.
A finished product’s regulatory status is inextricably bound to its intended use, its efficacy and its safety assessment in the target population. Thus, it is paramount to heed the regulatory status of any finished product in order to foster appropriate messages and expectations among consumers, patients, and healthcare professionals.
