At the recent IPA World Congress + Probiota in Copenhagen, Professor Simone Guglielmetti presented a new classification system for postbiotics: a ‘decision tree’ which differentiates postbiotics into four categories.
The work bridges decades of academic research, bringing together insights from key stakeholders, IPA members, regulatory agencies and global governments into one framework.
Defining postbiotics
Coordinated by the International Probiotic Association (IPA), the framework is the result of nearly two years of collaboration among academic and industry experts, with the first version launched in June at IPC2024 in Prague.
After receiving over 400 comments from stakeholders, the revised version now includes extensive input from global regulatory representatives.
“Establishing consensus at IPA is a must, which is why the first round of reviews took the time it did to address,” said George Paraskevakos, executive director of the International Probiotics Association (IPA). “Consensus is key because it establishes a unified foundation for scientific definitions, regulatory guidelines and industry standards, ensuring clarity, credibility and trust for the postbiotic category.”
When creating the framework, the first hurdle to tackle was the definition of a postbiotic. The academic definitions vary, as does the definition used in commercial products, with most failing to address various downstream technical, commercial and regulatory issues.
“Postbiotics have become evident as the ‘new kid on the block’ to many stakeholders,” Paraskevakos explained. “Although there are many definition papers on the category per se, what keeps regulators up at night were not really addressed in these scientific manuscripts.
“Key items such as manufacturing, analytical methodologies, the foundation of the progenitors, labelling criteria, safety, storage and stability, were regulatory concerns. This became increasingly apparent to me through my meetings with governments across the world when asking their position on this category.”
Speaking at the congress, Guglielmetti said that ‘postbiotic’ is a singular word with “several different meanings.”
“It’s not that one is wrong and one is correct, but it is important to address all the possible uses of the word,” he explained.
For the purpose of the decision tree, Guglielmetti defined a postbiotic as ‘any non-viable agents of microbial origin conferring a beneficial physiological effect’.
As well as the lack of consensus around a definition, there are also several different preparations and compositions of postbiotics, for example, the method by which bacteria are killed and separation techniques.
“So, the question is, how can we distinguish and classify these preparations?” Guglielmetti asked.
The decision tree
The decision tree for the classification of postbiotics follows a series of questions which lead the user down a path resulting in one of five outcomes:
- the product is outside the field of interest (i.e. not a postbiotic)
- the product is a postbiotic classified as fragmented microbial cells (FC)
- the product is a postbiotic classified as intact non-viable microbial cells (IC)
- the product is a postbiotic classified as complex non-viable preparations (CX)
- the product is a postbiotic classified as microbial metabolic products (MM)
To be classified as a postbiotic, the product must not contain live bacteria, must be intentionally inactivated and should not be intended to diagnose, treat, cure or prevent disease (to qualify as a food or dietary supplement).
Additionally, the progenitor must be approved by the regulatory authority for use in the intended category of the product. Alternatively, the safety status of the final ingredient must be approved by a competent authority.
Only products which meet all of the above criteria can be classified as a postbiotic, which can then be differentiated into one of the four categories.
FC postbiotics are made of intentionally fragmented microbial cells, separated from the culture medium, while IC postbiotics consist of intentionally inactivated (non-viable) whole microbial cells (i.e., mostly intact), separated from the culture medium.
CX postbiotics consist of an unpurified culture medium with non-viable microbial cells and/or cell fractions, and MM postbiotics consist of metabolic products of microbial cells within their unpurified or partially purified culture medium.
“One of the biggest changes we’ve made is surrounding purification,” Guglielmetti explained. “We received several comments from stakeholders which led us to conclude that metabolites which are purified from a growth culture are not postbiotics.”
Harmonizing standards and regulations
Guglielmetti says the decision tree can be applied to ingredients in marketed postbiotics to assess the safety, quality and efficacy of commercial products and to foster innovation in the postbiotic industry.
“We believe that harmonizing standard regulation [and] fixing clear criteria is really important to facilitate clear communication with stakeholders,” he told delegates. “But maybe the key point of this work is trying to avoid the whole postbiotic category as being perceived as a marketing gimmick.”
A ‘roadmap’ paper which discusses the commercial and regulatory frameworks for postbiotics is now ready for publication, Guglielmetti added.
“We are excited to continue our strategic efforts in advancing the probiotic category, as we build on our past successes and aim to drive progress in additional ‘biotic’ categories, including postbiotics,” Paraskevakos said.
