In 2017, FAO/WHO jointly released the FAO/WHO Guidelines for the Registration of Microbial, Plant derived and Pheromone Products for Plant Protection and Hygiene, in which it was clear that the types of products not covered include invertebrates or large organisms, transgenic and synthetic compounds that are consistent with natural structures. On this basis, FAO/WHO jointly released Chapter IX "Guidelines for the Development of Microbial Pesticide Standards" in the third revised version of the 2016 FAO/WHO Pesticide Product Standard Development and User Manual, which clearly covers bacteria, fungi and viruses, and viruses currently only focus on baculovirus. FAO/WHO has issued standards covering more than 300 active ingredients, but there are only 2-5 biological pesticide standards (different according to different definitions), including FAO standard azadirachtin and WHO standard BT subspecies of Israel; It covers 43 traditional chemical pesticide formulations and 6 microbial pesticide formulations. The microbial pesticide formulations only include mother drug (TK), granule (GR), wettable powder (WP), water dispersible tablet (WT), suspension agent (SC) and seed treatment suspension agent (FS).
Compared with traditional chemical pesticides, the data requirements for microbial pesticides applying for FAO/WHO product standards generally show the following characteristics: 1. Publicly published information can be cited as part of the data requirements, or application for report exemption can be made; 2. Methods that are self validated in the laboratory or verified by peer validation can be used, and there is no need to carry out large-scale collaborative validation experiments on the methods. The application for FAO/WHO * * standards for microbial pesticides does not need to apply for CIPAC analysis methods for active ingredients. 3. If possible, risk assessment can only be carried out for effective ingredients; 4. The test report may not be issued by the OECDGLP laboratory. 5. At present, the same product identification review for microorganisms has not been carried out, and the same identification for baculovirus may be carried out in the next step.
When applying for FAO/WHO pesticide product standards, microbial pesticides differ from traditional chemical pesticides in the following aspects:
1. Differences in qualitative methods of active ingredients
When applying for FAO/WHO microbial pesticide product standards, the effective ingredients of microorganisms should be identified to the strain level. The strain identification methods should be widely available under the conditions at the time of application, mainly including morphology, physiological and biochemical reaction characteristics and gene sequence. The strain sample code of the strain preservation center approved by * * should be submitted. At present, there are three strain preservation centers qualified as the Budapest Treaty * * Depository Center in China, which are respectively the General Microbiology Center (CGMCC) of the China Microbiological Culture Depository Management Commission; China Typical Culture Center (CCTCC) and Guangdong Provincial Microbial Culture Collection Center (GDMCC).
2. Differences in application materials of mother drug
Compared with chemical pesticide technical drugs, according to the characteristics of microbial pesticides, the data required only for microbial parent drugs include: storage stability data (determination of shelf life and supporting data) Microbial pollutant data (mainly refer to the OECD65 document, refer to the article "Screening and limit regulations of microbial pollutants in microbial pesticides", secondary compound information, preservation and maintenance of production strains, etc. Among them, the analysis method of effective components must be certified by the peer (ILV), and the analysis method of related impurities must be independently confirmed, but the confirmation criteria for quantitative methods of microbial pesticides recognized by * * are missing.
In addition to the toxicological characteristics, compared with traditional chemical pesticides, the toxicological and exposure data of microbial mother drugs also need to examine the pathogenicity and infectivity of microbial products. Occupational health supervision reports, acute oral/inhalation infectivity and pathogenicity, acute intravenous/intraperitoneal injection infectivity Cell culture test data and toxicological data of related secondary compounds (metabolites) (especially toxins); If there are negative effects published, especially clinical cases and follow-up research reports, they should also be provided.
3. Differences in application materials of preparations
Traditional chemical pesticide preparation products apply for the FAO product standard. On the premise that the used raw drugs have been evaluated by the FAO, the preparation products only need to provide the full batch testing data (except for WHO dosage forms such as slow release dosage forms and long-lasting mosquito nets). In contrast, the application for FAO standards for microbial pesticide preparations requires more information. In addition to batch testing data, product composition (confidential data), physical and chemical properties, determination of shelf life (regular storage data), 6 acute toxicity data and some ecotoxicological data should also be provided. For some quality control indicators, more loose limits can be considered according to the product characteristics, such as automatic dispersion and suspension rate can be allowed to be less than 60%, and wet screening indicators can be allowed to be more than 2%. In addition, the solid dosage form of microbial products may need to develop cold storage indicators. After storage, the content of effective ingredients shall be determined (only for products that may affect the stability of effective ingredients during low-temperature storage). After hot storage, only the physical and chemical indicators shall be tested, and the content of effective ingredients shall not be tested.