The growing interest in microbiome science has fuelled a surge in research on probiotics, leading to a deeper understanding of their role in human health. In 2024 alone, the International Scientific Association for Probiotics and Prebiotics (ISAPP) reported that over 10,000 papers were published on biotics and fermented foods, with approximately 30,000 publications in the broader field of microbiome science (3). This expanding body of evidence underscores the scientific community’s investment in understanding the complex interactions between probiotics and the human microbiome.

Despite their rising popularity, the term probiotic is often used inconsistently, with many commercially available products failing to meet scientific criteria regarding strain identity, safety, and efficacy (4, 5). Regulatory inconsistencies and varying substantiation requirements further complicate global commercialization and consumer education, creating challenges for both industry stakeholders and public health authorities. Addressing these concerns through standardized definitions, stringent quality controls, and harmonized regulations is critical to ensuring the credibility and effectiveness of probiotic products in the marketplace.

• Toxicological studies
• Allergenicity assessments
• Nutritional evaluations

EFSA introduced the concept of Qualified Presumption of Safety (QPS) to standardise a generic pre-assessment to support safety risk assessments. The QPS assessment is conducted separately from and independently of the safety assessment of a regulated product submitted for market authorisation. Therefore, having QPS status does not guarantee market authorisation. Nonetheless, if a product that requires a pre-market authorisation contains a microbial species that has QPS status, a simplified safety assessment may be done, that involves less data on potential risks as compared to a product containing a microbial species without QPS status (6). EFSA performs an extensive literature search and then updates the QPS list every 6 months. It is important to note that the GRAS status of ingredients, including microbes, has no regulatory status in the EU.

Safety Assessment

Safety remains the paramount concern for new probiotic strains for use in food supplements. EFSA has established stringent criteria for safety assessment:

• Long history of safe use in food or supplements without substantiated harm reports in healthy individuals
• Rare or isolated credible reports of infection or intoxication, limited to high-risk populations
• Organism identifiable to at least species level
• Availability of antimicrobial agents for treating potential infections
• Evidence of absence of biogenic amine production capacity

These criteria form the foundation for evaluating the safety of new probiotic strains, ensuring consumer protection while allowing for innovation in the supplement industry.

Strain Characterization and Storage

Proper characterization and storage of probiotic strains are essential to maintaining their safety, stability, and efficacy. Probiotic ingredient and supplement producers must ensure:

• Culture deposition in a recognized and accessible collection for traceability
• Storage of the master cell bank at -80°C to preserve strain integrity and prevent genetic drift
• Characterization of the organism at defined intervals to confirm strain identity and detect any genetic or microbial contamination
• Storage of freeze-dried powder ingredients under controlled conditions (e.g., low humidity, appropriate temperature) to maintain viability and potency

These measures ensure the consistency, purity, and effectiveness of probiotics throughout the production and shelf life of the product.

Production Process and Quality Management

It is essential that manufacturers of food supplements containing probiotics adhere to stringent quality control measures to ensure product consistency, safety, and efficacy. Key requirements include:

• Preservation of Microbial Integrity – The production process must not cause substantial changes to the properties of the microorganism(s) from the start of production to the final product, ensuring strain viability, stability, and intended functionality
• Adherence to Good Manufacturing Practices (GMP) – Manufacturing must comply with established GMP standards, incorporating rigorous quality assurance protocols at every stage, from raw material sourcing to final packaging
• Defined Shelf-Life and Stability Conditions – Comprehensive stability studies must be conducted to establish appropriate storage conditions that preserve microbial viability throughout the product’s shelf life
• Transparent and Accurate Labelling – Labels must clearly specify the minimum effective dosage, viable cell count (CFU) at the end of shelf life, storage recommendations, and verifiable health claims supported by scientific evidence
• Contamination Prevention and Quality Control – Regular testing must be conducted to ensure the absence of contaminants, including unwanted microbes, allergens, or environmental toxins, safeguarding product purity

These measures collectively ensure the consistent quality, safety, and efficacy of food supplements containing probiotics, providing consumers with reliable and effective products.

Probiotic Claims and Scientific Evidence

While the term “probiotic” remains contentious in EU regulations, scientific consensus has emerged regarding the requirements for probiotic claims:

• Safety assessment as a prerequisite
• Demonstration of strain viability (through appropriately designed stability studies)
• Randomized Controlled Trials (RCTs), observational studies, systematic reviews, or meta-analyses supporting general health benefits

These requirements ensure that claims are substantiated by robust scientific evidence. However, the EU’s regulatory framework presents significant challenges for the probiotic industry, particularly concerning health claims and product labelling. Under Regulation (EC) No 1924/2006 on nutrition and health claims made on foods, the European Commission considers the term “probiotic” as implying a health benefit, thereby classifying it as a health claim. To date, the European Food Safety Authority (EFSA) has not approved any health claims related to probiotics, resulting in restrictions on their use in marketing and labelling. Consequently, companies often resort to alternative terminology, such as “live cultures” or “fermented foods,” to indicate the presence of beneficial microorganisms while adhering to regulatory requirements (7).

This regulatory stance has led to inconsistencies across EU member states. Italy, Spain, France, Denmark, Poland, Bulgaria, the Czech Republic, Greece, Malta, and the Netherlands have now authorised the use of the term “probiotic” on supplement labels, either as a reference to their nutritional or physiological effects, or as a category name. While this is a positive step, it adds to creating a fragmented market and potential confusion for consumers. The lack of harmonization underscores the need for a unified EU approach to probiotic labelling and health claims, balancing consumer protection with industry innovation. Harmonization will also simplify compliance for manufacturers and promote the free movement of goods within the EU market.

The US, regulated by the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC), follows a more flexible regulatory pathway. Probiotics can be marketed as dietary supplements, functional foods, or medical foods, depending on their intended use and claims. The FDA does not require pre-market approval for dietary supplements containing probiotics, provided that manufacturers comply with the Dietary Supplement Health and Education Act (DSHEA) of 1994. Health claims can be made under the structure-function framework, allowing companies to state that probiotics “support digestive health” or “promote gut microbiota balance,” provided such claims are substantiated by credible scientific evidence and include disclaimers that they are not intended to diagnose, treat, cure, or prevent any disease.

The APAC region presents a diverse regulatory landscape, with some countries adopting policies that encourage probiotic innovation. Japan, for example, has long embraced probiotics within its Foods for Specified Health Uses (FOSHU) framework, which allows approved probiotics to carry health claims related to digestion and immune support. Similarly, South Korea and China have established regulatory pathways that recognize probiotic functionality, provided companies submit scientific evidence demonstrating efficacy. Australia and New Zealand, regulated by the Therapeutic Goods Administration (TGA) and Food Standards Australia New Zealand (FSANZ), respectively, also allow the use of the term “probiotic” in marketing, provided products meet safety and efficacy standards.

The disparity in regulatory frameworks across the EU, US, and APAC markets highlights the need for greater harmonization in probiotic regulation. While EFSA’s stringent criteria prioritize scientific rigor, they also limit consumer access to probiotic information and hinder market growth. Conversely, the more flexible US and APAC approaches enable innovation and consumer choice but may raise concerns about standardization and claim validity. A harmonized global framework that balances scientific evidence with market accessibility could enhance consumer trust, support industry development, and ensure consistency in probiotic health claims worldwide (8).

• Strengthening safety assessments and quality control to meet evolving regulatory expectations.
• Investing in rigorous scientific research to substantiate health claims with robust evidence.
• Enhancing transparency in labelling and marketing to provide consumers with accurate, verifiable information.
• Staying ahead of regulatory changes by actively monitoring updates and participating in harmonization efforts.

To sustain innovation while maintaining the highest safety and efficacy standards, industry stakeholders must engage with regulatory authorities, contribute to public consultations, and advocate for science-based policies. A collaborative approach will be essential in shaping a regulatory framework that fosters both consumer protection and industry growth.

Currently, the EU’s restrictive stance on probiotic health claims has forced companies to adopt alternative descriptors, creating regulatory inconsistencies across markets. This fragmentation underscores the urgent need for a unified policy that ensures consumer clarity while supporting the responsible development of the biotics sector.