Key Safety Criteria for Novel Microbial Food Ingredients: A Comparative Analysis of International Regulatory Frameworks

In the context of the research on food ingredients, "novel microorganisms (NMs)" refers to microorganisms without a documented history of safe consumption. The utilization of these novel microorganism-derived ingredients is expanding rapidly within the food and nutrition sectors, and such ingredients are broadly classified into three categories, live microorganisms, non-viable bacteria, and purified metabolites, each characterized by distinct risk profiles and unique regulatory requirements. Despite their growing prevalence, a globally harmonized protocol for safety assessment is currently lacking, leading individual nations to implement disparate safety frameworks within their respective regulatory systems. Consequently, this review aimed to provide a scientific foundation for the standardization of safety criteria by performing a comparative analysis of established guidelines from the European Union (EFSA), United States (FDA), Canada (Health Canada), Brazil (ANVISA), Thailand (Thai FDA), India (FSSAI), Japan (FSCJ), and Australia/New Zealand (FSANZ). Our analysis identified several universal safety parameters for live NMs, including hemolytic activity, antimicrobial resistance (AMR), toxigenic potential, the production of antimicrobial substances, metabolic profiling, and toxicological assessment. While toxicological evaluation, the production of antimicrobial substances, and the absence of live NMs were the consensus criteria for the safety evaluation of non-viable bacteria and purified microbial metabolites, an allergenicity evaluation is additionally required for purified microbial metabolites. Based on our analysis, this review proposed safety standards for novel microbial food ingredients including live microorganisms, non-viable bacteria, and purified metabolites by synthesizing these diverse regulatory landscapes.