The probiotic category is relatively young, and as an industry, it has faced its own hurdles around lack of guidance, self-regulation, IP, and more. However, regulations and product innovations have come a long way in recent years, including the FDA guidance for live biotherapeutics, paving a path for a new wave of products.

As the probiotic arena continues to mature, we are seeing the next natural phase of growth going beyond dietary supplements. Scientists, regulators, and stakeholders are asking questions along the lines of, “What other types of health products can be made of microorganisms?” and “Where can this industry further develop?”

We are seeing a divergence in the innovative solutions that respond to those very questions. The first group includes novel strains that are not traditionally in foods (such as ones isolated from the gut), and the second group is launching probiotics as applied biotherapeutics or pharmaceuticals.

Taking products down a drug development pathway offers many perks, including making therapeutic claims about your product. Historically, this approach has been very fruitful for companies able to enter the pharma world successfully.

While it might be challenging, it is possible. There are a handful of things to consider, including what label claims you would like to make (establishing a target product profile) regulatory strategy, pre-clinical program, clinical program requirements, manufacturing requirements, as well as if the company would like to move from nutra to pharma. Continue reading as we break down key strategies and considerations for these three sections so you can maximize your R&D efforts.

Label Claims
Working with your desired health claims is step number one. What would you like to say about this product? Once you discover that, you can see if that falls into the nutra or pharma world. Another consideration is the intention of the product, what do you want it to do? These are key questions that will help you determine if the pharmaceutical pathway is right for you.

FDA regulates substances on the intended use, not a single claim. Therefore, it’s the totality of product positioning, from product claims to website copy to clinical research endpoints that will determine its classification. For example, if you are doing clinical research and the endpoint being observed indicates a drug, then FDA will view your product as a drug. It is a fine line that many companies trip over: a probiotic used for diagnosis, cure, mitigation, treatment, or prevention of disease is a live biotherapeutic, regulated by the Center for Biologics Evaluation and Research in the U.S.

In the instance where a company wants to exist in both dietary supplement and drug categories, start in the dietary supplement framework to avoid creating regulatory barriers (e.g., being an adulterated product in the eyes of FDA) that would prohibit sale of your product. Regardless of what your optimal endpoint is, your desired claims will drive your clinical programming, and ultimately your product classification.

Clinical Programs
Clinical trial programs for products that will be moving from nutra to pharma are nuanced, but within reach. Most issues with probiotic clinical research result from poor planning and poor clinical trial design. Each aspect of the study must be meticulously designed to achieve reliable, beneficial results.

As you move from nutra to pharma, the clinical documentation becomes more rigorous. Clinical trials must be conducted under Good Clinical Practices (GCPs) as dictated by the FDA and ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use). To save time and money within your clinical research program, it’s imperative that all data is collected and coded in accordance with drug development standards to allow the pooling of data. This includes (but is not limited to): MedDRA coding for adverse events, CDISC and CDASH for data collection, and utilizing 21 CFR Part 11 compliant databases.

As per the FDA, “Relevance of using prior human data is based on similarity of product(s), study design, objectives and endpoints, number of subjects, level and duration of exposure, type and duration of monitoring and surveillance, integrity of study conduct, data collection, and subsequent analysis.”

Additional clinical requirements for biologic products include increased validation. Every item in your study protocol must be justified, for example, explaining why a blood draw is being taken, the validation on the analysis method for said blood draw, sample chain of custody, documentation for all aspects of sample integrity, among others. Good clinical practice (GCP) is a term thrown around the research industry but has specific meaning and requirements in the pharmaceutical industry that may not be mandated for the dietary supplement industry depending on regional regulations. 

Other guiding principles for clinical research include using qualified physicians, having qualified staff (experienced, educated, and effectively trained), recording all information appropriately following good documentation practices (GDP), and having a quality assurance program in place.

This is contrary to Canada, where Natural Health Products (NHPs) are regulated as a subset of drugs, and therefore the requirements mirror pharmaceutical trials a little more closely. Therefore, the expectation for research is to follow the drug rules, but not to the exact same levels. Therefore, companies developing therapeutic products should consider conducting proof of concept studies in Canada. Companies can explore some drug indications while maintaining NHP status, providing answers to the question, “is my product valid?” without the full investment of a drug, thus significantly reducing the cost of failure.

Nutra to Pharma
Achieving pharma status by launching as a supplement or NHP is a solid strategy for both validating and funding drug development. As previously noted, it is important to avoid regulatory barriers by properly planning your product development process and having a sound regulatory strategy.

Consider launching your proof of concept studies in Canada so you can avoid being classified as an Investigational New Drug (IND), which prohibits the sale of the product under dietary supplements in the U.S.

As one would assume, there are key differences between probiotics as dietary supplements and probiotics as live biotherapeutics. For example, Generally Recognized As Safe (GRAS) status for probiotics as food (since supplements are a subset of food), will do nothing for your safety status as a live biotherapeutic.

Manufacturing guidelines are different as well, with cGMPs for food (Parts 110-111) not being acceptable for a finished drug, including biologics, which require Parts 210-211 compliance.

In summary, probiotics are seeing a new period of growth and maturation for products to be launched as live biotherapeutics. Successful market access is possible with proper planning and an experienced team to help navigate the regulatory complexities of taking a single product through multiple pathways.

If you are interested in learning more about the regulatory strategies and approaches for launching natural-based products as pharmaceuticals, Nutrasource will be hosting the Nature to Pharma digital summit, an online event taking place on June 17, 2020. Our expert staff will be speaking about everything from marketing claims for supplements versus drugs, to product development strategies for introducing naturally-based pharmaceutical products. To learn more, visit www.nutrasourceevents.com.

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Josh Baisley, B.Sc., is vice president of clinical design and delivery at Nutrasource. With 20 years of experience in quality assurance, clinical, pre-clinical, and regulatory affairs for the natural health products sector, Baisley has been directly involved in nearly 100 clinical trials.