Reading Between the Lines: What the FDA Public Workshop Really Tells Us About the Regulation of Microbiome-Based Products

On September 17, 2018 hopes were high regarding the clarification of the regulatory framework as well as a potential decision or ambitions by the FDA to stimulate further discussion regarding microbiome-based products, as the agency organized a public workshop on the science and regulation of live microbiome-based products.

Our members and colleagues in the US were first in line to register. Hopes were also high in Europe, as the authorities on this side of the Atlantic are not as inclined to hold open dialogue with industry. The level of expectation and the importance of this growing space could be seen by the number of individuals attempting to register for the event, either in person, or by webinar, and numerous Europeans made the trek to Rockville, MD, or logged on to get a better understanding of the FDA’s expectations regarding microbiome-based products.

The workshop began by specifying that the microbiome is a rapidly evolving area and that recent progress have allowed for translation from fundamental science to application by the industry, therefore creating new opportunities and the development of new products with a positive impact on public health. As explained, this workshop aimed at starting a discussion with the scientific community and producers on the best approaches for this new type of products with two objectives in mind:

1) what are “well-characterized” products, and

2) what are “well-designed” clinical trials?

The objectives were ambitious: from Europe, we were hoping to see proactive participation on the part of the FDA representatives during the workshop and the ensuing discussions.

Unfortunately, it quickly became clear that science would overtake the regulatory conversation, and the level of participation of FDA representatives was relegated only to chairing sessions, without too much involvement in the topics on best practices, characterization, or clinical trial designs.

Science was indeed the focus of the meeting. The upshot to this was the fact that many diverse positions were brought to the attention of the audience regarding the efficacy and safety of microbiome-based products, which, from time to time, is precisely what the industry needs: often are we overpowered by excitement for the potential of our products, and sometimes forget that robust scientific evidence is required for registering them as drugs, and that their exciting potential is no substitute for a clear demonstration of efficacy and safety.

The status of probiotics was also thoroughly discussed in relation to the difference between food supplement and drug – as it is the rule in Europe, ‘intended use’ is the basis of regulatory status at the FDA level. And furthermore, whatever the history of use for a given is, when it is intended for use in humans with the goal of preventing or curing a pathology, such a product must be registered as a drug, and an IND is most often necessary for use in clinical trials.

At the PRI, we do not find this surprising; if we think about products marketed as food supplements in Europe, the safety status can be very positive in a general population. However, it is still necessary to demonstrate the safety of such products in the specific patient population for whom they are intended. And in Europe, in order to assess efficacy and safety of such products in a patient population, a clinical trial authorization should be obtained.

This clarification was important; we are perhaps finally coming to a point where the FDA and European framework (also for which the definition of a drug product is one that cures or prevents disease) are coming into alignment.

However, regarding the clarification of the regulatory status of food supplements, the presentation made by the CFSAN representative was a little disappointing as it did not include specific examples of microbiome-based products. Instead, it focused on the procedures, without taking into account the specific nature of these products and the challenges which probiotics represent for the FDA, if such challenges do exist.

Regarding the drug status, the presentation made by the CBER representative clarified the regulatory status for LBPs (Live Biotherapeutic Products) as well as FMT (Fecal Microbiota Transplantation), and as expected, the question of characterization was raised, as it was an objective of the workshop. However, if the guidelines on LBPs was explained regarding the CMC aspects, we were looking for a detailed discussion on what challenges they are facing in assessing these new types of products and what the industry should work on when it comes to providing critical information to the assessors. Once again, the high quality presentations allowed the audience to understand the position of different actors, developers, as well as clinicians, and their respective challenges, but at no point did the audience have access to a better understanding of the challenges that the assessors are facing, even if it is up to the industry to provide the responses to their investigations and therefore the right tools to document them.

In conclusion, we have to ask ourselves, “What was the added value of this workshop?”, as conferences in the field already showcase many of the speakers who made a presentation that day – and the answer is this: the insight generated by the clash of opposing views, which allows industry to verify on which aspects clinicians (and also probably assessors) are still expecting to see effort on the part of industry in order to thoroughly demonstrate safety and efficacy when it comes to administering these products to patients.

However, regarding the objectives of the workshop and the discussion between the scientific community and the industry, we were left wanting more due to the low-key involvement of the FDA representatives on the various panels, as their vision and experience could have been of critical value for the audience.

Finally, it is clear the FDA has realized the importance of the microbiome in medicine and how this will revolutionize the way we treat patients in the future.

The authority probably largely under-estimated the significance of the industry, as well as its level of expectations in terms of clarification of the regulatory framework: the workshop was fully booked in less than a week after announcement and additional arrangements had to be made for more participants to attend as well as live streaming to accommodate for the large number of people looking to attend from inside and outside the US.

We can therefore hope that the authorities are now aware of the wave coming towards them when it comes to new microbiome-bases products and the multiple indications in which proof of concept exist!

Dr. Magali Cordaillat-Simmons (PhD)

Scientific and Regulatory Affairs Director
Pharmabiotic Research Institute (PRI)