Guest Column | April 10, 2020

Choosing The Best Regulatory Pathway For Microbiome Products

By Jenna Phillips and Esther Ketelaars, PA Consulting


There is a regulatory grey area between healthcare and consumer health products, often introducing confusion to brands and consumers interested in the space. In the United States, the FDA regulates drugs and pharmacological therapeutics, as well as food, dietary supplements, and personal care products, albeit through different branches of the agency. As science advances and new products proliferate, the “old” rules must be reconsidered and updated as appropriate. The microbiome space is one area that is bringing new challenges to the agency, due to much of the science supporting microbiome product claims being very new and remaining unproven in many cases.

The FDA has previously struggled to make and enforce guidance for the consumer health industry. For example, in 2013, the genetic diagnostic company 23andMe received a warning letter from the FDA for displaying genetic health risks to its customers and was asked to remove the information from its website and future testing kits. Following the warning, 23andMe has worked hard to generate and compile the scientific evidence to support the health claims and reintroduce their reports to consumers. The 23andMe example demonstrates that consumer health companies that are selling products with health-related claims directly to consumers must be aware of the regulatory environment and take steps to comply with it, lest they risk sanction by the FDA and reputational damage.

Which Regulatory Pathway Is Best?

Microbiome analytics firms may need to play it safe by compromising on the health claims, focusing rather on “wellness” claims until they generate enough evidence to make therapeutic or diagnostic claims that are acceptable to the FDA. Dietary supplements often have a disclaimer on their packaging or marketing materials indicating that their product claims and information have not been evaluated by the FDA. While many probiotics and prebiotics are currently marketed as dietary supplements, companies are seeking additional accreditation for their products through further scrutiny from the FDA and other regulatory bodies.

To qualify as a legitimate medical product, probiotics and other microbiome modulating products must be tested in controlled human trials. While clinical trials are being performed, this is a new and complex research landscape, and all too often trials are not appropriately designed and lead to misleading or inaccurate claims. Indeed, researchers at the Sorbonne and Columbia University published a report in August 2018 reviewing 384 randomized clinical trials studying the use of probiotics, prebiotics, and synbiotics, and in their conclusions questioned the accuracy of adverse event reporting in studies of those products.1

Diagnostic applications of the microbiome, ranging from tests for acute infections to chronic inflammatory disorders, are also piquing the interest of investors and investigators. (For more on the factors driving the booming microbiome market, read our previous article.) In 2017 Nestlé Health Science entered into a joint venture with microbiome therapeutics company Enterome to accelerate the commercialization of tests for inflammatory bowel disease. The test is designed to complement a microbiome-targeting treatment being co-developed by Enterome and Takeda to treat Crohn’s disease, currently in Phase 1b development (NCT03709628). More research is certainly required to furnish healthcare providers and consumers with the evidence that microbiome testing and modulation have long-term, large-scale promise in disease management.

However, even with more extensive research, focusing on wellness claims may be the near-term reality for companies interested in entering the microbiome market since gathering the evidence for medical-level health claims is also complicated by the highly diverse nature of the microbiome between individuals and the variety of effects a live microbial product can have on the complexity of an individual’s gut and overall health.

Insufficient medical evidence and regulatory limits can restrict companies from moving into medical-grade products, but there is an opportunity for companies to split the difference and consider dividing their business into two: a consumer arm and a medical arm.  Consumer interest and willingness to try unproven products provides companies with opportunities to fill the gap between medical-grade products and those for consumer health indications only. This is already being done in the field of the microbiome. AOBiome recently spun off its consumer skincare brand known as Mother Dirt to enable the parent company to focus on FDA approved treatments for specific clinical outcomes. AOBiome is driving live biotherapeutic treatments for skincare with ongoing Phase 2 trials for eczema and rosacea and a planned Phase 3 trial for acne.

While the overall regulatory process is less complex for non-therapeutic products, careful consideration should be given to the status of any microbial components used, as well as how any health claims will be substantiated. Given the current lack of regulatory guidance surrounding microbiome-based products, developers should not only anticipate agency requests for information to better characterize new innovations but also work proactively to generate data in support of claims. For example, the FDA may require chemistry, manufacturing, and controls data to characterize any products classified as “novel” components of food, of which probiotics are frequently classified.

Moreover, while a product’s classification is largely dictated by its intended use, in some instances different regulations may apply to the same ingredient, depending on its form, amount, or sourcing. Whether a company seeks to earn medical-grade review of a microbiome-focused product or is content with wellness-focused claims, understanding the regulations, the science, and the market is key to a successful microbiome-based business model.

When And How To Engage With Global Regulators

The big opportunity presented by the microbiome for advancing therapeutic and non-clinical health and wellness products is matched only by the daunting task of navigating a regulatory environment not yet adapted to the rapid pace of development in the field. In many cases, microbiome-based therapies represent an entirely new category of treatment, lacking an established pathway to follow and presenting developers with the prospect of forming working partnerships with their respective authorities.

In 2012, Rebiotix piloted this approach as the first company to engage with the FDA in defining a regulatory framework for RBX2660, a fecal microbiota transplant (FMT) therapy for recurrent Clostridioides difficile (Cdiff) infections.2 Working extensively with the Center for Biologics Evaluation and Research (CBER) to establish stringent donor guidelines and screening standards for its drug platform likely aided Rebiotix in obtaining priority designations from the FDA (Fast Track, Orphan Drug, and Breakthrough Therapy) and in avoiding others’ costly missteps: most recently, in June 2019 the FDA issued a safety alert and suspended several ongoing clinical trials for FMT therapy after the use of stool from an improperly screened donor resulted in a patient death.3

Complicating this landscape, however, is the fact that governmental collaboration is rarely a one-size-fits-all endeavor. Companies seeking to commercialize microbiome products in the global market must face the ongoing challenge that regulatory authorities, policies, terminology, and definitions differ by country. The EU, for example, lacks a centralized classification system for treatments based on microbiomes collected from healthy donors and, as such, decisions regarding the regulation of new medical therapies like FMT fall to each individual national authority. This absence of harmonized regulatory guidance has led to most of the active clinical trials using FMT in Europe being supported by academic institutions rather than industrial ones. Thus, while there is a clear business case for engaging with the government, developers must remain savvy — balancing choices that impact cost and time-to-market with the unique opportunity to shape new policy.



About The Authors:

JennaJenna Phillips is a consumer health expert at PA Consulting focused on growing great businesses and brands in the health and wellness sector. Her background in public health and nutrition and experience working with organizations as diverse as food companies, dietary supplement brands, personal care and fitness gives her expertise in the area of probiotics and their function for consumer application. Connect with her on LinkedIn.


EstherEsther Ketelaars is a life sciences expert at PA Consulting. She supports life sciences companies in differentiating their therapies and further personalizing medicine through innovative approaches, such as the use of digital measures in clinical studies. With her background in Immunology and Microbiology at ETH Zurich, she is leveraging her combined expertise to explore the opportunities the microbiome presents to personalize healthcare. Connect with her on LinkedIn.