Microbiome

Considerations on the development of pharmaceuticals and foods designed to favourably impact the human microbiome – health claims, legislation and development.

Introduction

A microbiome describes the collection of microbial life (microbiota) that inhabit a specific environment, and include microorganisms as diverse as bacteria, yeasts, fungi, archaea and viruses. In man, these organisms are resident primarily in the gastrointestinal tract, but also occur on the skin, genitals and in the lungs. As our understanding improves of the role these microorganisms have in the development of obesity, gastro-intestinal diseases, depression and allergies, the possibility now exists to address these, and other, health challenges from a new perspective. This includes the development of new foodstuffs to maintain beneficial gut flora, together with the development of new drugs that offer more targeted possibilities.

Clearly, these options are not mutually exclusive, and both options have benefits, constraints and challenges.

Legislation and classification

A fundamental difference between pharmaceuticals and food relates to strict regulatory definitions:

  • A medicinal product is a substance or combination of substances presented as having properties for treating or preventing diseases, or that may be used in or administered either with a view to restoring, correcting or modifying physiological functions, or to making a medical diagnosis[1].

  • A food product can be any substance or product intended to be ingested by humans. This includes any substance intentionally incorporated into the food during its manufacture, preparation or treatment (e.g. the addition of “prebiotics” such as special dietary fibre to stimulate the growth of microorganisms in the gut, or the addition of “probiotics” such as live bacteria in yogurt, dairy products, and pills)[2]. In particular a substance that was not significantly consumed on a market in the past years may be qualified of “novel” or “new”. It is not permissible to claim or imply that food can treat, prevent or cure any disease or medical condition.

Other factors that are considered by legislators to differentiate between a drug and a food include the presentation of the product, its’ composition, health claims, mode of action and target population.

To examine how this classification might work in practice, take the example of a presentation containing a combination of substances (including a bacterial strain), that has been shown to have a beneficial effect on human health (Table 1).

How presentation and claim can impact product classification

FOOD

DRUG

Powder formulation. Claim - beneficial nutritional properties related to the components of the formulation

Powder formulation. Claim - to restore the immune function through metabolic action

Liquid formulation, oral administration. Claim - to complete the nutritional needs of patients with impaired digestive function

Liquid formulation, i.v. administration. Claim - to prevent degradation of the digestive function of patients

Pill. Claim – to maintain a normal blood cholesterol concentration

Pill. Claim - to restore normal blood cholesterol concentration

It can clearly be seen that the claim requested, the presentation and route of administration can all impact product classification.

Considerations in developing products in this arena

Regulatory approval can be very straight-forward for food products, as they require at most simple notification - possibly completed by applications in specific cases (e.g. health claims, novel foods). Production must be performed in accordance with the relevant applicable quality system (e.g. ISO 22000, GMP).

However, the current lack of specific guidance and recommendations should be considered, as this can make it difficult to satisfy an Authority’s expectations. For example, CMC data may be necessary to characterize substances used in a foods’ production, and the possibility that a significant amount of data might be required in the development of a food, in the case of significant innovation such as a new health claim approval, should be anticipated.

In addition, care must be taken regarding labeling claims. Whilst it is not permissible to make a claim relating to treatment, prevention or cure, food can be labeled to associate it with a health property e.g. one of its components can be associated with the reduction of a risk factor for a disease.  Although claims must be approved by the appropriate Competent Authority (e.g. EFSA, FDA), they are less onerous to demonstrate compared to medicinal claims, as the extent of any claim will be much more limited.

The regulatory process for drugs is more complex, as approval from the Competent Authority (e.g. FDA, EMA) is required before marketing. The procedure is expensive and time-consuming, relying on the submission of extensive data sets, analyses and expert opinions to demonstrate appropriate quality, safety and efficacy, and that a favorable risk/benefit exists in the identified patient population. However, several incentives are available that can make this process more attractive to the manufacturer, including accelerated pathways for marketing authorization, advice from the Competent Authorities, financial incentives, and periods of market and data exclusivity.

Similar incentives are not usually open to innovative food developers, although it may be possible to benefit from the protection of proprietary data submitted to support a new health claim or novel food application, provided such data were critical for the assessment.

Finally, it should be noted that post-market surveillance is applicable for both food and drugs, although as expected, a full pharmacovigilance system with mandatory serious event reporting is much more rigorous in the case of drugs.

Conclusion

By manipulating the Human Biome, it may be possible to modify the course of some diseases. Agents that have an influence on the human biome include medicinal products and foods developed with this end-point in mind.

However, differences in regulatory requirements mean that developing a drug is significantly more onerous, long and expensive than the development of food. The positive trade-off is that an approved drug potentially gives access to a wider range of indications, provides the opportunity to tackle more specific health issues and permits access to a market with less competition in the field of microbiome.

To facilitate the development of products in this area, it is therefore recommended to pay attention to any health claim you wish to make, the target population, budget and development timelines.


1- Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use - OJ L 311, 28.11.2001, p. 67–128
2- Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety - OJ L 31, 1.2.2002, p. 1–24

Marielle Fournier, Pharm.D, Senior Director, Drugs, Devices & Combination Products

As Senior Director, Marielle has several responsibilities within the management of projects involving the design and implementation of global regulatory strategies for the development, evaluation and marketing of medical devices & medicinal products, as well as combination products (i.e. drug/device, including combined ATMPs) and borderline products. She actively participates to the redaction and review of ATMPs and Combined ATMPs US/EU dossiers. She closely follows the evolution of new regulations.

Clara

Clara Desvignes, Senior Regulatory Scientist

As a senior regulatory scientist at VCLS, Clara is involved in the development of microbiome-related health products, both in the medical and food area. Clara earned an engineering degree majoring in Sciences and Technologies of human biology, nutrition and food, at AgroParisTech, France. She also studied specialized food products in the University of Milan, Italy, as part of her engineering’s degree. Prior to joining VCLS, and as part of her engineering degree, Clara worked for 6 months at RNI-Consulting (Angers, France), where she gained particular experience in the areas of for nutritionals and nutraceuticals