The 2020 edition of the Chinese Pharmacopoeia is gradually in line with the international level, and has revised and supplemented the contents of microbial strain management, strain verification, strain typing, strain traceability, microbial monitoring in the production process, and environmental microbial monitoring, etc., which puts forward new requirements and challenges for Chinese pharmaceutical enterprises in microbial monitoring and management.According to customers' needs, CICC provides technical services to pharmaceutical enterprises in the control of microorganisms in the production process, as well as the detection of new drug application and production strains.

In 2018, the National Health Commission of the People's Republic of China issued the "National Standard for Food Safety Strains for Food (Draft for Comments within the industry)", which is the first national standard specification for strains for food in China.Food culture refers to "one or more living microorganisms (including bacteria, fungi and yeasts) that can be used in food by fermentation culture, isolation, drying or not drying."According to the use, it is divided into direct edible bacteria and food fermentation bacteria." Companies "shall use strains that have been identified as safe after safety evaluation to ensure that they do not cause any acute, subacute, chronic or other potential hazards to human health." In the same year, the "Hygienic Standards for the Production of strains for Food Use (Draft for Comments)" issued by the company made more detailed provisions on the requirements of strains for food use: "The original strains purchased by the company or the strains separated and collected by itself should be identified and genetic stability test."

CICC summarized the relevant services for the identification of strains for food with new resources, and CICC will better serve the government supervision and industry needs, and escort the declaration of strains for food enterprises.

The regulations on feed and feed additives in China are constantly being upgraded, refined and standardized. According to "Regulations on the Administration of Feed and Feed Additives (revised in 2017)", developers or production companies must submit an approval application to the agricultural administrative department of the State Council before commencing production of new feeds and feed additives. They are also required to provide samples of the new feed or feed additive, as well as information such as name, main ingredients, physical and chemical properties, developing methods, production processes, quality standards, testing methods, inspection reports, stability test reports, environmental impact reports, and pollution prevention measures.

The "Administrative Measures of New Feeds and New Feed Additives (revised in 2016)" stipulate that application materials for new feeds and new feed additives include identification reports of the effective constituents, physicochemical properties, and chemical structure of the effective constituent, or taxonomic (strain) identification reports of animal, plant or microorganism. For microbial fermentation products, reports identifying the strains used in production should also be provided.

In addition, both the "Requirements on Application Materials for New Feed Additives" and the "Requirements on Application Materials for Registration of Imported Feeds and Feed Additives" state that safety assessments of production strains should be conducted for microorganisms and their fermented products, except for strains generally recognized as safe. The revised "Requirements for Application Materials of New Feed Additives" (Announcement No. 226 of the Ministry of Agriculture and Rural Affairs) was officially implemented on December 4th, 2019. The announcement explicitly states that reports identifying the microbial strains used in microbial feed additives and the production of feed additives at least to the level of species or subspecies shall be provided. For feed microbial additives and microbial strains used in the production of feed additives, safety of the strain shall be evaluated. Through microbial phenotypic test, molecular biology test and whole genome sequence (WGS) analysis, combined with relevant literatures,to evaluate the pathogenicity and toxic metabolite production ability of the strains to be evaluated (for feed additives produced through microbial fermentation, the toxic metabolites produced by production strains shall be measured) and antimicrobial resistance was comprehensively evaluated.

CICC is willing to actively cooperate with feed companies, providing assistance in the application of microbial strains for new feeds/feed additives, and committed to offering professional, efficient, and enthusiastic services to enterprises in the feed industry.

Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The health-care functions of probiotics are strain-specific, and sufficient amounts need to be consumed to achieve the expected health-care effects.

The “Declaration and Review of Probiotic Health Food (Draft)” released in 2019 requires applicants to provide “research reports with functional effects at the strain level” and “strain identification report (includes phenotypic characterization and strain-level identification results based on genotyping)”. At the same time, it is stipulated that “the number of viable bacteria of each type in probiotic health foods shall not be less than 10⁶ CFU/mL(g) during its shelf life”, and “the biological, genetic and functional characteristics of the strains used should be clear and stable, the strains and their metabolites must be non-toxic and harmless”. In the same year, the “Pathogenicity Assessment Procedure of Strains for Health Food (Draft)” was issued and stipulates that enterprises must “provide standardized and scientific taxonomy information (genus, species, strain name or number)”. Bacterial species identification data should include “information based on phenotypes or the latest gene sequencing technology to accurately identify microorganisms to the species level” and the assessment results of “animal pathogenicity tests” and “toxin production tests”. The “Toxicological Assessment Procedure of Health Food and Its Raw Materials (Draft)” stipulates that “health foods with special regulations for probiotics, fungi, etc., should add corresponding tests according to regulations, such as bacterial pathogenicity tests”.

In May 2019, both the Chinese Institute of Food Science and Technology and the Chinese Nutrition Society issued a scientific consensus on probiotics, emphasizing that the number of viable bacteria and strain specificity should be the key characteristics of probiotics.

CICC is a professional probiotic identification and safety assessment service organization. In June 2019, the China Center of Industrial Culture Collection (CICC) successfully passed the “Special Food Verification and Evaluation Technical Institution Registration” of the State Administration for Market Regulation (formerly the China Food and Drug Administration), which marks that CICC has obtained the national statutory license to provide strain identification and strain virulence testing for health food companies and issue third-party testing reports, the registration number is TY06211652. CICC will better serve government supervision and industry needs and promote the healthy development of the health food industry.

China's "14th Five-Year Plan" for the development of bioeconomy proposes to develop synthetic biology technology and realize the iterative upgrading of the food industry. Making every effort to tackle tough problems in life and health, biological breeding, basic raw materials, etc., and accelerating breakthroughs in key core technologies is the key to fundamentally changing the pattern of core technologies in key fields in China being controlled by others. At present, the safety evaluation regulations of genetically modified microorganisms at home and abroad are gradually improving and refining, which is of important guiding significance for the declaration of synthetic biology raw materials for enterprises. The Administrative Measures for the Safety Evaluation of Agricultural Genetically Modified Organisms (2022 Revision) stipulates that the safety evaluation of genetically modified microorganisms for animals should include the taxonomic status, safety evaluation, genetic stability, plasmid status, plasmid stability and potential danger of the recipient microorganisms; The safety evaluation of gene manipulation should include the nucleotide sequence and derived amino acid sequence of the target gene, the copy number of the inserted sequence, the physical map of the target gene and the vector, and the name and source of the vector. In addition, the General Office of the Ministry of Agriculture issued the "Guidelines for the Safety Evaluation of Genetically Modified Microorganisms for Animals", which stipulates that "genetically modified microorganisms for feed refer to functional proteins or peptides (such as phytase, antimicrobial peptides, etc.) expressed in bacteria, viruses, mammalian cells, yeast and other systems as feed additives." Genetically modified microorganism (GMM) products can be purified proteins, live GMM or inactivated GMM. The overall evaluation requirements should include: molecular characteristics, genetic stability, biological characteristics of genetically modified microorganisms, safety of genetically modified microorganisms to animals, humans, and the ecological environment. According to customer needs, CICC provides overall solutions for the preservation, identification, research and development and safety evaluation of genetically modified microorganisms and their products, helping enterprises complete product compliance declarations and escorting the safety of genetically modified microorganisms.

The publication of novel microbial species has a profound impact on the research of microbial systematics. More than 800 papers reporting novel taxa were published on International Journal of Systemic and Evolutionary Microbiology (IJSEM) in 2017, of which more than 300 papers were published by Chinese authors, accounting for about 40%. Since 2018, IJSEM has required authors to provide the whole genome sequencing (WGS) information when publishing taxonomic descriptions. CICC has rich experience in novel microbial species identification service and provides "one-stop" technical solutions, including type strain introduction, strain identification and analysis, public preservation, technical consultation, etc. The testing items have passed ISO 17025 laboratory accreditation, the test results are internationally recognized, and the data reliability is guaranteed. We have served our clients by publishing over a hundred papers reporting novel species on IJSEM.

With the rapid evolution of modern biotechnology, the emergence of novel microbial testing methods has become a hallmark. These methods offer advantages such as rapid simplicity, high sensitivity, and efficiency, driving the need for validation and standardization. Recognizing this, international organizations like ISO and AOAC, along with national government bodies, have issued standards and guidelines (refer to Table 1). As the industry moves towards these innovative methods, the importance of validation cannot be overstated. Validation studies for alternative methods are systematic, professional, and interdisciplinary. However, in China, there is currently a dearth of publicly available cases applying relevant standards for method validation, highlighting a critical gap that needs attention. The CICC research team, with our extensive experience in industrial microbial detection, preservation of standard strains, and a robust technology development and validation system, stands at the forefront of addressing this need. Our ongoing efforts have yielded promising results, demonstrating the potential of alternative methods in microbial testing. To further catalyze the integration of these technologies into the industry, CICC is extending comprehensive services to developers and users of alternative microbial testing methods. This includes technical services, commissioned research and development, and collaborative projects encompassing solution design, research implementation, statistical analysis, research reports, research papers, and industry expert reviews. We welcome inquiries and look forward to collaborating on the future of microbial testing.

Contact Persons: Yuan Yuan Ge; Xiao Ying Jiang

Phone: 010-53218303/15010084337; 010-53218302

Email: lucy@china-cicc.org; tech@china-cicc.org.