IFF to bring “new class” of strictly anaerobic probiotics to market

31 Mar 2023 --- Recently, IFF successfully scaled production of a strict anaerobic probiotic strain. According to the company, this identifies a new microbiome solution and establishes the safe and efficient production of a newly-discovered, proprietary, gram-negative Akkermansia probiotic species at the lab, and at industrial scale.

Moreover, the company emphasizes that this capability allows for solutions that can improve immunity, insulin sensitivity and the gut barrier function.

IFF further states that this new capability of producing this strain of probiotic at scale had long been a challenge due to its complex and specific nutritional requirements and says its success demonstrates the company’s fermentation capabilities, downstream processing and formulation abilities within the probiotic space.

To understand more about this milestone, NutritionInsight speaks with Sebastian Stahl, Director for Process R&D at IFF, Oliver Hasselwander, Principal Scientist and Technical Fellow at IFF and Benoit Palms, Head of Strategy, Licensing & Business Development Human Microbiome at IFF.

Can you provide more information about the specific benefits of this next-generation probiotic strain and how it differs from existing probiotics on the market?
Hasselwander: There is no strict scientific definition of what constitutes a next-generation probiotic. Generally, we see these strains as a new class of probiotics based on strains that are naturally living in the human digestive tract. They are called commensal bacteria.Hasselwander notes that this represents a new class of probiotics, based on strains naturally living in the human digestive tract.

They go beyond the more traditional probiotics like lactobacilli or bifidobacteria, and because they reside in the colon – which is a very anaerobic environment – they have to be able to grow in the absence of oxygen. That’s one key element.

The other key element for this probiotic is that, because they live in the colon and originate from the human digestive tract, they are well adapted to that environment. When you use them as probiotics, they will be able to adjust to that ecosystem, be able to grow in that ecosystem and be able to show their properties and health benefits in that ecosystem.

How did IFF develop the technology and processes needed to produce the strict anaerobic probiotic strain at an industrial scale, and what were some of the biggest challenges faced during this process?
Stahl: Strict anaerobic strains pose very new challenges regarding media composition, selecting specific growth and harvest conditions. I was very proud of the team that we were able to master some of these new challenges.

We had to rethink our standard approaches and the things that we know from producing standard probiotics, conventional probiotics or dietary supplements. We had to think about how to handle material and also rethink our approach when it comes to final formulation.

Meeting internal specifications regarding count and improving stability is, we believe, paramount for future success in this space. That was a kind of tricky undertaking, to make sure we got the highest possible count and the stability that we need.

Can you discuss the safety and regulatory considerations associated with producing and marketing a new probiotic strain, and what steps has IFF taken to ensure that this product is safe and compliant with relevant regulations?
Hasselwander: I think the first thing to say is that the safety assessment – does not in principle differ from the traditional safety assessments that we do in any case.

These strains reside in the intestine in a healthy adult population. There is no reason to assume they are unsafe. Rather, they have coevolved to live with us. Nonetheless, we apply a very rigorous safety assessment which has various elements.Palms explains that partnerships help to bring solutions that meet the unmet needs of the end users, consumers or patients quicker.

This includes genomic safety assessment, where we look at the genome and see whether there are antimicrobial resistance genes or virulence genes. Then we do a number of in vitro and in vivo toxicology studies and, eventually, a human study where we look at tolerance as well as safety in humans.

That’s the same approach that we apply for all of our probiotics, not only to the next generation one. Any difference in the regulatory pathway would be determined by the intended use. These strains, at least from our perspective, go into food supplements as mentioned before.

For a next-generation probiotic, this could mean Novel Food Regulation applies in the EU and we have to submit a dossier to the European authorities. And in the US, it will require the establishment of what is called a GRAS (generally recognized as safe) status, but these are standard regulatory frameworks that we are well equipped to deal with.

Additionally, the industry as a whole has adopted these safety testing standards. The regulatory authorities will ask the same questions to every company that would like to market a probiotic and I think these are “must have” capabilities to be active in this space.

How does IFF plan to commercialize its extensive microbiome pipeline, and what role do strategic partnerships and investments in R&D play in this strategy?
Palms: IFF is a B2B company. For every product that we want to commercialize, we rely on commercial partners. Commercial partners could be health and wellness types of companies, and pharmaceutical companies because the microbiome has gained a lot of interest and investments as well, not only from venture capital, but also from the pharma and biotech industry.

We partner for commercialization purposes, but we also enter into strategic partnerships earlier in the development process of the product. These strategic partnerships are based on a risk and profit-sharing model.

Stahl underscores that the team had to rethink standard approaches and what they know from producing standard probiotics.That means that both parties will jointly invest in the development of that project, and this could be on a 30/70 basis, or 50/50 or 70/30 – whatever ratio is feasible. The investment per project is decreased while sharing the risk of the development with the other party.

The advantage here is actually that we leverage our capabilities and expertise, and we can also access innovative technologies from our partners. That means that we can bring a stronger pipeline of assets to the market together with our partners meeting the unmet needs of the end users, consumers or patients.

Stahl: When you think about recent years, IFF made significant investments in the dietary supplement business both in the US and in Europe. It also spent money on acquisitions such as Health Wright Products in 2022. These investments span from the very upstream part of the fermentation, right down to formulating a finished format, which is critical to delivering some of these strains to an end consumer.

What’s next for IFF?
Hasselwander: We have end-to-end capabilities in the microbiome space. We have an isolate collection of these next-generation probiotics of several thousands of strains and we have the tools to characterize these strains by: using multi-omic approaches, screening assays and preclinical models, particularly in the areas of metabolic, gut and immune health.

We have gut simulation and immune models allowing us to study microbial host interaction and then, based on this solid data set together with the safety assessment, we can progress these kinds of strains into clinical studies.

When you pair this with this new capability to actually manufacture anaerobic strains at scale, it allows us to develop additional solutions in the future.

By William Bradford Nichols