In 2017, China promulgated series of new pesticide regulations and significantly raised the market threshold with added data, elevated criteria and narrowed acceptance scope. It is also the first time that MoARA will have to disclose quality standard code and testing method for registered pesticide, which constitute an important part of product chemistry data. Mr. Huang Qiliang from Chinese Academy of Agricultural Sciences joined CRAC 2018 conference in Chengdu to summarize and compare the critical points in dossier preparation for traditional chemical pesticides and biopesticides, as well as introduce the latest official guidelines for pesticide testing and method validation.
General requirements on product chemistry data
Product chemistry data mainly consists of component identity information, general information on technical material and product composition, component analysis, production process, physical-chemical properties, component analysis, quality specification, method validation, explanation on quality specification developing, test report of storage stability, quality test report and method validation report, as well as packaging, storage and transportation information etc. These requirements differ with product type and origins, which were specified in the Annex I and Annex II to the “MoA Announcement 2569- Data Requirements on Pesticide Registration:
ANNEX I Tables of definitions and instruction on the data requirements for the registration of TC/TKs (chemical, biochemical, microbial and botanical);
ANNEX II Tables of definitions and instruction on the data requirements for the registration of formulated products (chemical, biochemical, microbial and botanical);
"Overview of Product Chemistry Data Required for Pesticide Registration in China"
1. Product (component) identities
All types and origins of pesticides are required to submit product (component) identity information including: common names, generic names approved ISO or other international organizations, chemical names, CAS numbers, CIPAC codes, develop codes, empirical and structural formulae, isomer ratios, MW molecular weights and ranges (noted with the issuing date of the Relevant Atomic Mass Table used) of active ingredient, stabilizer, synergist and other limitative components. If the active ingredient exists in certain form of salt compound such as sodium glyphosate, identity on the salt compound should be provided accordingly.
All types and origins of pesticides are required to submit product (component) identity information including: common names, generic names approved ISO or other international organizations, chemical names, CAS numbers, CIPAC codes, develop codes, empirical and structural formulae, isomer ratios, MW molecular weights and ranges (noted with the issuing date of the Relevant Atomic Mass Table used) of active ingredient, stabilizer, synergist and other limitative components. If the active ingredient exists in certain form of salt compound such as sodium glyphosate, identity on the salt compound should be provided accordingly.
Biological characteristic information will be additionally required for microbial TKs:
The common name, international common name (usually Latin name), taxonomic information (e.g. species, genus, family, subspecies, strain, serotype, pathovar and other microbial relevant nomenclatures):
Report of strain identification issued by national authoritative institution engaged in microbial research;
Code of microbial strain (the preservation number in the microbe bacterial preservation administration center);
For genetically modified microbial, the applicant shall submit additional information or supporting materials on genetic engineering technique, inserted or deleted gene fragment(spectra of nucleotide sequence or restriction endonuclease), new characteristic compared with the parent strain, genetic stability in nature, certificate of GMO license and genetic background;
If a botanical pesticide was extracted from single plant species, the product can be named either by the name of the active ingredient or the common name of the raw material plant plus the word “extract”. But the characteristic active ingredient should be explicitly defined. If the botanical pesticide was extracted from multiple plant species, it should be named with the characteristic active ingredient. If a botanical formulation was process from a TC/TK that has been exempted from TC/TK registration, applicant of the formulation shall provide the complete production process, component analysis report, quality control indicators and specification of the TK/TC. If the TC/TK has ben approved by other Chinese authorities for the uses in pharmaceutical, food or health food, etc., aforementioned data can be exempted but photocopies of the certificate of the approval and product quality specification will be required.
2. TC/TK information and product composition
General information on TK/TC and product composition are required for all formulated products:
Information on the producer(s), registration status and quality control index of the TC/TK(s) used in the formulated products.
The chemical names, CAS numbers, molecular and structural formulae, contents, functions of components utilized in the formulated product. For mixture of solvents or adjuvants expressed in product code, the sourcing origin, composition and safety information (e.g. MSDS) will be required. For inert with specific function, such as safener, stabilizer and synergist etc., the quality specification, basic physical and chemical properties, sourcing origin and safety information (e.g. MSDS), information on the usages in overseas countries should be provided. If a co-formulant (adjuvant separately package and on-site prepared prior to the final use), the composition and information aforementioned should be provided separately.
3. Production process (processing method)
Information on production process (processing method) differs with product type and origins.
Data on Production Process Required for Pesticide Registration in China
4. Physical and chemical properties
Physical and chemical data on active ingredient, TC/TK and formulated products of all origins are summarize as follows:
"Data on Physical and Chemical Properties Required for Pesticide Registration in China"
5. (Full)-component analysis
Applicant need to conduct component analysis report of all TC/TKs and conclude the cause formation of all detected and possible impurities through chemical theory, raw material and production process, as well as other aspects. The new regulation firstly defines toxicological and eco-toxicological impurities to be analysis quantitatively analyzed for chemical and biochemical TC/TK.
"Pesticides Componnent Analysis Required for Pesticide Registration in China"
6. Product quality specification
Both TC/TK and formulated product require a quality specification including basic indicators and other quality control indicators relevant to the product origin and formulation type:
"Data on Product Quality Specification Required for Pesticide Registration in China"
7. Quality testing method and method validation
The applicant should provide at least one method for the testing of active ingredient in TC/TK and formulated products. If chemical method was utilized, at least 2 method should be provided. If the active ingredient exists in certain form of salt compound, the method should be capable of determination the nature of the salt. For the testing of other components, The applicant should provide the complete method including: summary, mechanism, information of test item and reference standard, preparation of solution, operating condition, procedures of measurement, result calculation, statistical method and tolerance, etc. Testing of other quality indicators should comply with the “Guidelines on Validation of Analytical Methods for Agrochemicals”.
8. Explanation on the developing of product quality specification
The applicant need to make an explanation on the basis and rationality of these quality indicators, which was specified in the Annex to MoA Announcement 2569. For other formulation type not yet specified, the applicant may establish the indicators can be developed in accordance with the specification developed by FAO or WHO. For novel formulation type, the indicators can be established in accordance with characteristic of active ingredient, application method, safety property and other aspects and authentication report on the new formulation type should be provided.
9. Storage stability data
2-years' room temperature test on 1 batch of product will be required for chemical, biochemical and botanical formulations. If the product in 1 batch was packed in different package. For microbial formulation, the stability test can be conducted for designated period and temperature, such as 21 year at 20-25℃ or 2 years at 0-5℃.
10. Test Reports of product quality and method validation
Quality test and method validation test should be carried out in China. The former shall include all quality indicators submitted in product dossier. Testing facility that issues the quality test report should validate the testing methods for active ingredient, relevant impurity, safener, stabilizer, and synergist and other limitative component and issue a validation report and validation on method for other quality indicators may not be required. A validation report should include: experimental condition provided by the sponsor, experimental condition actually adopted by the testing facility (e.g. chromatographic parameters and sample preparation, etc.) and explanation on the deviation, results and standard deviation of all parallel determination and typical chromatograms (reference standard and sample), as well as feasible evaluation.
Guideline and information referable for the developing of quality standard and method validation
There are over 40,000 pesticides registered in China, but only 20% of them have been established with national or industrial quality standard, while the rest of them are established with enterprise standard. Testing methods are usually not validated, which threatens the quality of agricultural inputs. Furthermore, most pesticide importing countries have elevated technical barrier to pesticide importation such GLP data, internationally accepted methods and validation of non-officially method. To improve quality management and international competitiveness, the rationality and feasibility of quality indicators are highlighted in China’s new pesticide regulation. The CRAC audiences are also shared with technical guidelines on how to develop quality standard and conduct the tests, as well as method validation.
ANNEX XI of MoA Announcement 2569: principles For the Nomenclature of Pesticide Products
ANNEX XII of MoA Announcement 2569: Content Ranges Of Active Ingredient(s) In Pesticide Products;
ANNEX XIII of MoA Announcement 2569: 13-Quality Specification and Physical and Chemical Properties Required For Different Formulation Type;
Food and Agriculture Organization(FAO)/World Health Organization(WHO):Standard and control projects（specification);
NY/T 2989-2016: Guidelines on developing the specification of pesticide for registration-product specification;
NY/T 1860.1-38-2016: Guidelines on the determination of physico-chemical properties of pesticides;
NY/T 2886-2016: Procedure for batch analysis of technical material
NY/T 2887-2016: Guidelines on validation of analytical methods for pesticides
