How can we effectively manage the registration of identical active ingredients under China’s new pesticide regulations?

According to the “Requirements for Pesticide Registration Data,” the registration of chemical pesticide technical materials (active ingredients) is categorized into registration of new technical materials, registration of non‑identical technical materials, and registration of identical technical materials.

Among them, Compared with the registration of new active ingredients and non‑equivalent active ingredients, the registration of identical active ingredients requires significantly fewer test data and incurs lower costs, and the registration process can be shortened from approximately four years to about one year. 。

As for how to successfully register an identical active ingredient, the key is to adhere to the requirements set forth in Annex 10, “Criteria for Identifying Equivalent Pesticides,” of the “Requirements for Pesticide Registration Data.” This entails conducting thorough reviews of registration criteria, making informed judgments on the equivalence of data, and preparing the requisite registration documentation. Additionally, it is important to closely monitor the approval procedures of the Pesticide Inspection Institute under the Ministry of Agriculture and Rural Affairs to enhance the likelihood of a successful registration.

Same active ingredient registration requirements
 

When selecting the same type of pesticide, you must choose… The first registration of this pesticide active ingredient has now exceeded its six-year protection period; applications for the same active ingredient must be evaluated against the original active ingredient, which was registered in accordance with the new “Requirements for Pesticide Registration Data.” 。

Rules for Identifying the Same Active Ingredient
 

In accordance with the requirements of Annex 10, “Criteria for Identifying Equivalent Pesticides,” under the “Requirements for Pesticide Registration Data,” the assessment of equivalent active‑ingredient data is conducted in two stages: the first stage involves the evaluation of product chemistry data, and the second stage covers toxicological and environmental impact data.

▲ Product Chemical Information Verification

When the product subject to application for recognition (M2, hereinafter the same) meets all of the following requirements, it may be recognized as being identical to the reference product (M1, hereinafter the same).

 01  The content of the active ingredient in M2 shall not be less than that in M1.

 02  The limit for M2-related impurities shall not exceed that of M1.

 03  The control targets for other major items under M2 shall not be lower than those of M1.

 04  Compared with M1, M2 contains no new related impurities.

 05  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.

 06  Compared with M1, M2 contains no new unrelated impurities.

 07  The results of the Salmonella typhimurium/Mutation Reversion Assay for M2 were equal to or better than those for M1.

When none of requirements 1, 3, or 7 is met, M2 is classified as a non‑identical active ingredient.

When requirements 1, 3, and 7 are all met, but none of requirements 2, 4, 5, or 6 is satisfied, a second-stage assessment shall be conducted.

▲ Toxicological and Environmental Impact Data Assessment

Toxicological Data Assessment

Toxicological data indicate that, compared with the corresponding test results for M1, the acute toxicity test results for M2 have a factor no greater than 2 (or, if greater than 2, do not exceed a reasonable dose‑escalation factor), and the evaluation conclusions regarding both positive and negative findings are consistent. Accordingly, the toxicological data are deemed equivalent.

If the results of the acute toxicity study do not establish equivalence between the toxicological profiles of M2 and M1, further evaluation shall be conducted on the results of repeated-dose studies (ranging from sub‑acute to chronic toxicity) as well as on reproductive toxicity, mutagenicity, and carcinogenicity studies, with classification in accordance with the principles set forth in Section 2.1.1.

If the target organs of toxicity are the same and the changes in the no-observed-effect levels (NOELs) and no-observed-adverse-effect levels (NOAELs) do not exceed the range of variation across dose levels, the toxicological data are considered equivalent.

Environmental Impact Data Verification

Under the condition that the test organisms are identical, and using the results of M1’s avian acute oral toxicity test, fish acute toxicity test, Daphnia magna acute immobilization test, honeybee acute contact toxicity test, and silkworm acute toxicity test as reference, if the corresponding test results for M2 and M1, when compared against each other, 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.

Requirements for Registration of the Same Active Ingredient
 

M1 Manufacturer’s name and registration certificate number.

M2 manufacturing process, full‑component analysis report, physicochemical properties, product quality specifications, and Salmonella typhimurium/Reverse Mutation Assay data.

Provide M2 toxicology and environmental impact data as required:

01 Toxicological Data:

Acute oral, dermal, and inhalation toxicity tests; eye irritation test; skin irritation test; skin sensitization test.

Subchronic (or chronic) toxicity studies (including a 90-day rat feeding study; additional 28-day dermal or 28-day inhalation toxicity studies shall be provided as appropriate to the product’s characteristics), mutagenicity tests, in vitro mammalian cell gene mutation assays, in vitro mammalian cell chromosomal aberration assays, and in vivo mammalian bone marrow micronucleus assays.

02 Environmental Impact Information:

These include: the avian acute oral toxicity test, the fish acute toxicity test, the Daphnia magna acute immobilization test, the honeybee acute contact toxicity test, and the silkworm acute toxicity test.

Where authorized by the holder of the M1 registration certificate, an original authorization letter signed by the authorized legal representative and affixed with the official seal must also be provided.

Approval Process for Identical Active Ingredient Data
 

When reviewing registration dossiers for the same active ingredient, the Quality Review Division, the Toxicology Review Division, and the Environmental Review Division each issue their respective professional review opinions and also render conclusions on equivalence. During the comprehensive review conducted by the Pharmaceutical Administration Division, the equivalence determinations from the quality, toxicology, and environmental reviews are consolidated, and a determination of product equivalence along with a comprehensive review opinion is then formulated.

Therefore, when preparing registration dossiers for the same active ingredient, it is essential to accurately determine whether the substances are indeed identical and to assemble a complete set of registration documents to ensure successful registration.

Source: WeChat Official Account: Agrochemical Compliance 24/7