It is well known that the research and development of new pesticides is difficult, costly, and long-term, but the creation and listing of new pesticides is crucial to our pesticide industry and agricultural development. Many old pesticide varieties are highly toxic and have been used for decades, and their resistance has become very serious. To eliminate these old varieties, new varieties that are more environmentally friendly, safer and more efficient must be launched. The requirements for registration materials of new pesticides in my country have become very high. As the threshold for registration review is getting higher and higher, the registration of new pesticides has become more difficult. In addition to the product itself being better, it has become more important to grasp the requirements for new pesticide registration materials and review standards, which also puts forward higher requirements for pesticide registration personnel. This article breaks down the five main challenges of new pesticide registration in China from a technical and policy perspective.

1. Radiolabeled metabolic assay

Previously, because many pesticide registration laboratories in China did not have the ability to do radiolabeled substances, the metabolism test of new pesticide technical drugs did not require the use of radioactive labels to complete. With the improvement of the technical level of domestic laboratories, from last year, the soil aerobic metabolism test, soil anaerobic metabolism test and water sediment metabolism test report of the new pesticide technical drug all require the use of radiolabeled substances to complete. In addition, in the registration of new pesticide formulations, metabolism tests in plants and metabolism tests in animals need to be completed according to the different registered crops. Similar to the environmental metabolism test of the original drug, it also needs to use radioactive labels to complete. Since there are relatively few test units with qualifications and sufficient experience to carry out radiometabolism tests in China, new pesticide research and development companies not only need to bear the high cost of radiolabel synthesis and metabolism tests, but also need to bear the uncertainty of test results. Once the number of main metabolites detected in pesticide metabolism tests is relatively large, the cost of pesticide registration tests will increase exponentially, because these main metabolites will also be required to carry out corresponding toxicological and environmental tests.

2. Main metabolite toxicology test

The toxicology section of the 2017 edition of the "Pesticide Registration Information" does not provide clear toxicological test requirements for related impurities and major metabolites and degradation products. The Institute for Drug Control of the Ministry of Agriculture and Rural Affairs has proposed that relevant impurities and major metabolites and degradants need to be provided according to different requirements. Test report; if the expert review believes that the results of the first-stage toxicology test show toxicological significance or the tests performed are insufficient to determine whether the metabolite is toxicologically significant, a second-stage, more advanced toxicity test needs to be carried out. This greatly increases the uncertainty of time and cost when new pesticides are registered. If a chemical pesticide original drug detects many major metabolites in the three major metabolic tests of plants, animals and the environment, the new drug can basically be declared a death sentence. Even if companies can afford the cost of Phase 1 trials, this is only the starting point for metabolite toxicology testing, and once a metabolite shows toxicological significance, move on to advanced Phase 2 trials?

3. Stricter evaluation criteria for new pesticides

Under the new pesticide management regulations, the approval of pesticide registration is based on the conclusion of risk assessment, but the requirements for new pesticides are obviously stricter. For example, the primary risk assessment of bees in the environmental risk assessment of a pesticide product. However, the old product may be listed on the label to avoid the flowering period and can pass the registration review, but the new pesticide needs to carry out a high-level semi-field experiment on bees to optimize the risk assessment. Or proven safe for bees. Generally speaking, if a new pesticide cannot pass the primary risk assessment (mainly referring to the applicator and the environment), and there is no good optimization strategy to pass the advanced risk assessment or lack of effective risk reduction measures, it is a high probability event to be required to carry out advanced tests .

4. Mutual recognition of data (MAD) and 28-day inhalation toxicity

According to the "Measures for the Administration of Pesticide Registration", the registration test report should be issued by a registration test unit recognized by the Ministry of Agriculture and Rural Affairs, or issued by a relevant overseas laboratory that has signed a mutual recognition agreement with relevant departments of the Chinese government. Experiments closely related to environmental conditions and registration experiments of China's endemic biological species should be completed within China. However, as of now, there are no relevant overseas laboratories that have signed mutual recognition agreements with relevant departments of the Chinese government. Therefore, under the current policy conditions, all registration test reports completed by overseas laboratories cannot be used for pesticide registration in China, which greatly increases foreign investment. Difficulty for agrochemical giants to register new active ingredients in China. There are many test items required to complete the registration of a new active ingredient original drug and preparation, and the cost is high. The common practice of major foreign companies is to complete a set of test data in foreign OECD GLP laboratories for submission and registration in various countries, including China. According to China's current policy, if major foreign companies want to register new active ingredients in China, they can only repeat many tests in China, especially safety-related toxicology and environmental tests. Repeating these tests is not only a matter of cost and time, but also if there is a big difference between the test results of the domestic laboratory and the overseas test results in individual key tests, it will directly affect the registration of the product overseas, which has a great impact on the enterprise. risks of. For foreign giants, one of the problems that makes the registration of new pesticides is the 28-day inhalation toxicity test. In the pesticide registration data requirements of most countries in the world, the 28-day inhalation toxicity test is not a mandatory test data, but in China's pesticide registration data requirements, it is the test data that must be submitted for the registration of new pesticides. This test is far from being completed in 28 days as it sounds. The test period is relatively long, usually 6-9 months, and the results are also quite uncertain.

5. New pesticide registration protection period

The "Pesticide Management Regulations" stipulates that the state shall protect the undisclosed test data and other data submitted by applicants who have obtained pesticides containing new compounds for the first time. Within 6 years from the date of registration, if other applicants use the data specified in the preceding paragraph to apply for pesticide registration without the consent of the applicant who has obtained the registration, the registration authority will not register; Except for the data. Therefore, if a pesticide research and development enterprise registers a new pesticide with a patent that has expired or is about to expire, and only has a 6-year registration data protection period after registration in China, the enterprise must consider whether the registration cost can be recovered in such a short time. At the same time, if a foreign company wants to issue a certificate of origin of the original drug to a domestic company within the 6-year protection period of the new pesticide to complete the registration of a non-identical formulation, it also needs to submit the registration information according to the new pesticide formulation. Data requirements Even if there is a certificate of origin of the original drug issued by the first new pesticide technical drug, it is necessary to submit the plant metabolism test and animal metabolism test data of the preparation, but the cost of the test is high. summary

It is an indisputable fact that it is becoming more and more difficult to register a new active ingredient in China under the new regulations, especially chemical pesticides. Biological pesticides, including microbial pesticides and biochemical pesticides, have relatively low requirements for registration information, and the situation will be slightly better. Various technical and policy problems will be encountered in the actual registration of new pesticides, far beyond the five challenges mentioned in this article. Here we would like to applaud all the companies who dare to create new pesticides and the regulations and technical personnel responsible for the registration of new pesticides. Despite the difficulties of registering new pesticides, the rewards of successful registration can be enormous.