Quick Guide to Pesticide Registration: Summary of Key Details on the Recognition Criteria for Identical Active Ingredients and Formulations

Release Date:

2018-08-22

With the promulgation and implementation of the new Regulations on Pesticide Administration, the Measures for the Administration of Pesticide Production Licenses, and Announcement No. 2569, the costs, difficulties, and timelines associated with pesticide registration have all increased significantly. To minimize registration expenses as much as possible, recognizing identical active ingredients and formulations during the registration process is a viable approach. However, following the introduction of these new policies, what specific standards must such identifications meet? Below, we provide a brief summary. Summary of Key Criteria for Identifying Identical Active Ingredients In line with internationally accepted regulatory requirements, the identification of identical active ingredients is governed by the provisions set forth in Annex 10 of Announcement No. 2569.

　　With the new… Pesticide Regulations on Administration, and Pesticide The promulgation and implementation of the Measures for the Administration of Production Licenses and Announcement No. 2569, Pesticide The costs, complexity, and duration of registration have all increased significantly. To minimize registration expenses as much as possible, recognizing identical active ingredients and formulations during the registration process is a viable approach. However, following the implementation of the new policy, what specific standards must such recognition comply with? Below, we provide a brief summary.
　　Summary of Detailed Criteria for Identifying the Same Active Ingredient
　　In accordance with internationally recognized regulatory requirements, the assessment of the same active ingredient is conducted in two phases, as stipulated in Annex 10 of Announcement No. 2569: the first phase involves the evaluation of chemical data, and the second phase covers toxicological and environmental impact data.
　　Phase I Assessment: Chemical Data Review of the Product
　　When the product seeking recognition (M2, hereinafter the same) meets all of the following requirements, it may be determined that M2 is identical to M1, in comparison with the reference product (M1, hereinafter the same).
　　① The content of the effective ingredient in M2 shall not be less than that in M1.
　　② The limit for M2-related impurities shall not exceed that of M1.
　　③ The control targets for other major M2 components shall not be lower than those for M1.
　　④ Compared with M1, M2 contains no new related impurities;
　　⑤ Compared with M1, the relative increase in the limit for non‑related impurities in M2 shall not exceed 50%, or the absolute increase shall not exceed 0.3%; the larger of the two values shall be used for evaluation.
　　⑥ Compared with M1, M2 contains no new unrelated impurities;
　　⑦ The results of the Salmonella typhimurium/Mutant Reverse Mutation Assay (M2) are equal to or better than those of M1.
　　When any one of requirements ①, ③, or ⑦ is not met, M2 is classified as a non‑identical active ingredient. When requirements ①, ③, and ⑦ are all satisfied, but any one of requirements ②, ④, ⑤, or ⑥ is not met, a second‑stage assessment shall be conducted.
　　Phase II Determination:
　　1. Toxicological Data Assessment
　　① Compared with the corresponding test results for M1, the toxicological test results for M2 show that the acute toxicity test result coefficient does not exceed 2 (or, if greater than 2, remains within a reasonable limit of dose‑escalation), and the evaluation conclusions regarding both positive and negative findings are consistent. Accordingly, the toxicological data are deemed equivalent.
　　② If, based on the results of the acute toxicity study, equivalence of the toxicological profiles of M2 and M1 cannot be established, further evaluation is required for repeated-dose studies (ranging from sub‑acute to chronic toxicity) as well as for reproductive toxicity, mutagenicity, and carcinogenicity studies. If the target organs of toxicity are identical and the no observed effect levels (NOELs) and no observed adverse effect levels (NOAELs) do not vary beyond the range of dose levels, the toxicological profiles shall be considered equivalent.
　　If, during the toxicological data evaluation stage, Step 1 is passed, the substance is deemed to be the same active ingredient; if Step 1 is not passed, proceed to Step 2.
　　2. Determination of Environmental Impact Documentation
　　If, based on toxicological data, equivalence between the toxicological profiles of M2 and M1 cannot be established, equivalence of the environmental impact data must also be assessed. Under the condition that the test organisms are identical, using the results of M1’s avian acute oral toxicity test, fish acute toxicity test, Daphnia acute immobilization test, honeybee acute contact toxicity test, and silkworm acute toxicity test as reference points, if the corresponding test results for M2 and M1, when compared, yield a ratio no greater than 5 (or, even if greater than 5, do not exceed a reasonable dose‑response scaling factor), then the environmental impact data for M2 and M1 may be deemed equivalent.
　　As can be seen from the relevant regulations, the identification procedure for the same active ingredient may proceed step by step; once it has been determined to be the same active ingredient, subsequent steps may be discontinued, thereby significantly reducing testing costs. Therefore, it is important to remind all parties… Pesticide Enterprises, when conducting Pesticide When registering an active ingredient, it may be worthwhile to determine whether it can be recognized as the same active ingredient, thereby reducing registration costs. Meanwhile, at present, all… Pesticide All enterprises must clearly recognize that the prerequisite for determining equivalence of an active ingredient is as follows: the complete set of registration data for the reference active ingredient (M1) required to establish equivalence must be based on Announcement No. 2569. Pesticide “Registration Documentation Requirements”: Only a complete set of documents independently prepared will be accepted.
　　It is also worth noting that microbial active ingredients and plant‑derived active ingredients (technical grades) are not eligible for registration as original active ingredients.
　　Summary of Detailed Criteria for Identifying the Same Pharmaceutical Product
　　1. First, the determination of identical formulations is divided into two categories: authorized and non-authorized.
　　1) Authorization: The review shall focus on the completeness and compliance of the authorization, as well as the equivalence of the active ingredient. Where authorized by the holder of an already‑registered product registration certificate, a formulation may be deemed equivalent if the source of the active ingredient is the same or if the active ingredient used has been recognized as identical.
　　2) Non‑authorization: The assessment procedure likewise proceeds in two stages. The first stage involves the evaluation of product chemical data, while the second stage covers toxicological and ecotoxicological data. Only formulations that simultaneously meet the requirements for chemical identity as well as demonstrate equivalence in toxicological and ecotoxicological profiles may be considered identical.
　　Phase I Assessment: Product Chemistry Data Review (All criteria must be met)
　　a) The active ingredient used in M2 is the same as that used in M1;
　　b) M2 and M1 have the same active ingredient content and dosage form;
　　c) The types and contents of restricted components, such as safety agents, stabilizers, and synergists, are identical in M2 and M1;
　　d) The control indicators for other major items under M2 shall not be lower than those under M1;
　　e) M2 shall not contain any additives that are expressly prohibited by national regulations, and the types and maximum permitted levels of additives subject to national restrictions shall comply with the relevant requirements.
　　Phase II Assessment: Toxicological and Environmental Impact Data Review (All criteria must be met)
　　① Toxicological data assessment
　　The toxicological test results for M2, when compared with the corresponding test results for M1, show that the acute toxicity test coefficient does not exceed 2 (or, if greater than 2, remains within a reasonable limit of dose‑escalation), and the evaluation conclusions regarding both positive and negative findings are consistent. Accordingly, the toxicological data are deemed to be equivalent.
　　② Determination of Environmental Impact Documentation
　　Under the condition that the test organisms are identical, using the results of M1’s avian acute oral toxicity test, fish acute toxicity test, daphnia acute immobilization test, honeybee acute contact toxicity test, and silkworm acute toxicity test as reference, if the test results for the corresponding endpoints in M2 are compared with those in M1 and the ratio does not exceed 5 (or, even if greater than 5, remains within a reasonable limit based on the experimental dose‑response factor), M2 and M1 may be deemed to have equivalent environmental impact data.
　　2. Documentation Requirements
　　① Where authorized by the holder of the M1 registration certificate, the original authorization letter, signed by the authorized legal representative and affixed with the official seal, together with the registration number of the active ingredient used in M1, shall be provided.
　　③ If not authorized by the holder of the M1 registration certificate, the following documentation shall be provided:
　　M1: Name of the manufacturing enterprise and registration certificate number; M2: Registration certificate number of the active ingredient used, product composition, description of the manufacturing process, physicochemical properties, and product quality specifications; M2: Toxicological data, including acute oral, dermal, and inhalation toxicity tests, eye irritation test, skin irritation test, and skin sensitization test; M2: Environmental impact data, including acute oral toxicity test in birds, acute toxicity test in fish, acute immobilization test in Daphnia magna, acute contact toxicity test in honeybees, and acute toxicity test in silkworms.
　　As can be seen from the relevant regulations, the approval procedures for identical pharmaceutical products differ significantly depending on whether they are authorized or non‑authorized. Therefore, it is important to remind all parties here… Pesticide Enterprises, when conducting Pesticide When evaluating the equivalence of formulations, it is advisable to determine whether an authorization can be obtained, so as to prepare the registration dossier more strategically. It is worth noting that: microorganisms Pesticide Formulation, plant-derived Pesticide Formulation, Biochemistry Pesticide Rodenticide formulations are not eligible for the same‑formulation recognition.