New pesticide registration in China is applicable for pesticides containing active ingredients that have not yet been approved for registration in China, including new pesticide TC (TK) and new pesticide formulations. The applicant applying for new pesticide registration shall submit the registration applications for both new pesticide TC and new pesticide formulations, as well as reference samples of the pesticide in accordance with the Administrative Measures for the Registration of Pesticides.
Since the implementation of the new Pesticide Registration Data Requirements, pesticide registration has become a risk-oriented pesticide safety assessment mode, with increased test data requirements, extended technical assessment period, high registration costs, and with uncertainty in China. It to some extent inhibits the registration of new pesticides, but pesticide enterprises still have internal motivation for new pesticide registration.
1. The Inevitable Trend of New Pesticide Registration
(1) Policy orientation
On January 29, 2022, the Ministry of Agriculture and Rural Affairs, together with relevant national ministries, formulated the 14th Five-Year Plan for the Development of National Pesticide Industry, which pointed out the direction for the development of pesticides.
a. Adjust the structure of pesticides. Follow the requirements of major pest control and pesticide reduction, and the latest requirements of the Guidance Catalogue for Industrial Structure Adjustment and Environmental Protection Comprehensive Directory, support the development of new chemical pesticides with high efficiency and low risk, vigorously develop biological pesticides, and phase out old pesticide varieties and formulations with strong resistance, low efficacy and high risk.
b. Establish a pesticide R&D innovation system and promote green pesticide R&D. To meet the needs of prevention and control of major diseases, pests and weeds, strengthen the original innovation of low-risk chemical pesticides such as new insecticides, fungicides and herbicides, make full use of synthetic biology technology to intensify research and development of microbial pesticides and botanical pesticides. Encourage innovative applications of nanotechnology in pesticide formulations.
(2) The market needs new pesticides and green pesticide registration.
Based on the green development philosophy and people's yearning for a better life, the demand for safe and diverse agricultural products is increasing, which proposes higher requirements for the green and high-quality development of the pesticide industry.
The structure of existing pesticides is aging, about 70% of which have been registered and used for more than 15 years. Issues like highly homogeneous, increased resistance, residue and environmental risks make it urgent to speed up the upgrading of pesticides and to eliminate highly toxic and high-risk pesticides.
In addition, major diseases and pests occur more frequently and severely, posing threat to food security. Thus it is an arduous task to prevent and control diseases and pests, and it leads to an urgent demand for new pesticide products.
(3) Pesticide enterprises need new products.
On one hand, promote production intensification of domestic pesticide enterprises, encourage merger and reorganization, transformation and upgrading of pesticide production enterprises, making them bigger and stronger. On the other hand, the launch of new pesticide products is the growth point of sales or profits of enterprises. In addition, China's efforts to protect intellectual property rights have been continuously strengthened, and China will treat the intellectual property rights of domestic and foreign-funded enterprises equally, further stimulate the innovation vitality of the whole society and continuously optimize the business environment, giving domestic and foreign enterprises the motivation to register new pesticides.
2. Macro Management of the Whole Process of New Pesticide Registration
The registration of new pesticides is costly, risky and time-consuming. The following three stages should be properly completed in order to manage the whole process of registration and improve the probability of approval.
1. Well establish the registration project, accurately evaluate the registration success rate, i.e. risk pre-assessment.
2. Supervise the whole process of the tests.
The whole test supervision process includes the preparation and sealing of test samples, selection of laboratories, test filing, signing test contracts, reviewing test plans, test supervision, reviewing test reports and timely collection of reports, etc. The tests involve product chemistry, toxicology, efficacy, residual eco-toxicology and environmental behavior tests, covering a wide range of fields. Some of the tests are complex, demanding and difficult. Once adverse result occurs, it will affect the registration in China and even all over the world. Therefore, toxicology, environment and residue experts should supervise the whole process of the tests to reduce adverse results.
3. Record and summarize the registration data, scientifically explain and response to the problems of products or data, so as to establish a set of complete and scientific registration data.
3. New Pesticide Registration Plan for Enterprises
New pesticide registration plan is the evaluation and risk control of the potential project. Enterprises should first evaluate the success rate of new pesticide registration projects, that is, risk pre-assessment for registration projects. There should be a criteria for potential registration projects on approval success rate. The success rate varies based on the anti-risk capability of enterprises. If the success rate of registration is significantly reduced due to policy changes in the future, it may cause cancellation and delay of registration projects.
To establish a registration project, the cost and period should be accurately estimated, market investigation should be made after the product is launched, sales volume and price in the next few years should be predicted, so as to form the benefit evaluation of the new project. When there are significant changes in registration fees and period, for example, the overall cost of the project changes by more than 10%, or when the registration period greatly changes, it will lead to reevaluation of the project, or even cancellation or suspension of the project.
Therefore, it is necessary to ask a professional team or consulting company with abundant experience in new pesticide registration to perform risk pre-assessment and provide reliable cost and period estimation, so that enterprises can make excellent project risk control.
4. Tests that Greatly Affect Registration
Based on the level of difficulty and importance, some tests which are rarely carried out in China with high technical requirements, long test periods and high costs will have a great impact on the registration.
1. Radiolabeled plant metabolism test, animal metabolism test and environmental fate test.
According to the new Pesticide Registration Data Requirements, radiolabeled plants metabolic data of 3-5 crops should be provided as residue data for the registration of new chemical pesticides. If the registered crops are animal feed or food, the metabolic test data of radiolabeled animals should also be provided. Soil aerobic metabolism test, soil anaerobic metabolism test and water-sediment system aerobic metabolism test in environmental fate tests should also provide radioactively labeled substance test of active ingredients. These kinds of tests are time consuming, greatly difficult and expensive. They are used to determine the residues and major metabolites in the environment, which affect the residual tests and trigger toxicity test of major metabolites, soil aerobic metabolism test, soil anaerobic metabolism test, water-sediment system aerobic metabolism test, analytical methods and validation tests of metabolites in water and soil, environmental toxicology tests of metabolites, and environmental risk assessment. The test results will have an impact on product registration in China and globally.
2. Subchronic toxicology tests, special toxicity tests and toxicokinetic tests.
According to the new Pesticide Registration Data Requirements, the registration of new chemical pesticides requires subchronic oral toxicity tests, subchronic (acute) dermal and inhalation toxicity tests, chronic toxicity and carcinogenicity test data of two rodents, teratogenicity test data, reproductive toxicity test data and toxicokinetic test data of two mammals. Due to the high requirements for laboratory, animal and feeding conditions, long test periods and high costs, the test results will affect the establishment of ADI, toxicological health risk assessment and dietary risk assessment, and even affect the registration of the product in China and all over the world.
5. Preparation of China's Pesticide Registration Data
After the test/risk assessment is completed, the project enters the next stage of data collation, preparation, and summary. How to ensure the scientificity and integrity of pesticide registration data so as to pass the technical review of ICAMA and relevant experts is one of the key missions of registration.
Firstly, check the integrity of the registration data in accordance with the Pesticide Registration Data Requirements, registration policies and relevant normative documents. This process is also the review and reconfirmation of registration project planning, test report and data preparation.
Secondly, each product has its own characteristics. The key is to integrate product chemistry, toxicology, efficacy, residues, environmental behavior and eco-toxicology data, TC data and the finished product data, find out the relationship between them. It helps to scientifically explain and deal with the problems that may occur in the evaluation. For example, the relationship between the physical and chemical properties of TC and the environmental fate of TC, the physical and chemical properties of finished product and some toxicology tests and some environmental toxicology tests, efficacy and residue, some environmental toxicology test and health and environmental risk assessment, residue and toxicology, environment behavior and risk assessment with toxicology, etc.
Finally, it is very important to ask experts and agencies with rich experience to review the registration data again after the data are ready.
6. Current Challenges of New Pesticide Registration
1) Toxicology data of major metabolites
According to the new Pesticide Registration Data Requirements, when registering new chemical pesticides, it is required to provide toxicity data of residue and major metabolites in the environment to evaluate whether the metabolites are related metabolites. At present, ICAMA requires acute oral toxicity, AMES, in vitro chromosome aberration and in vitro gene mutation, and a 90-day sub-chronic oral toxicity test. These tests require to provide a large quantity of metabolite samples, which are difficult to synthesize. These tests are also time consuming with uncertainty, which seriously affect the registration of new chemical pesticides.
In 2020 and 2021 under the new policies, many new chemical pesticide registrations were not approved because of the toxicity data of metabolites. The ICAMA is researching and discussing on solutions of this issue. Hopefully proper policies will be introduced, which can both scientifically evaluate major metabolites and solve the problems of new pesticide registration for enterprises.
2) Mutual acceptance of domestic GLP data and OECD-GLP data (MAD)
At present, China's GLP data and OECD-GLP data can’t be mutually accepted. Overseas OECD-GLP data can’t be accepted for pesticide registration in China, and overseas pesticide enterprises need to conduct a full set of local GLP tests in China for pesticide registration. While domestic enterprises need to re-generate GLP data in the OECD-GLP laboratory if they want to apply for registration abroad, even if they have completed the whole process of GLP tests in China. It increases the registration cost for both domestic and foreign enterprises, and affects the registration of new pesticides in China for domestic and overseas enterprises.
In March 2021, the China Pesticide Industry Association, China Veterinary Drug Industry Association and CropLife of China jointly organized an online seminar on OECD Good Laboratory Practice (GLP), Test Guidelines and Mutual Acceptance of Data (MAD). It aims to enhance the understanding of OECD GLP norms and test guidelines in China's pharmaceutical, cosmetics, veterinary drugs, pesticides, industrial chemicals, new chemical substances and food additive industries, strengthen the exchange of mutual acceptance between China and OECD, and promote the construction and development of GLP system in China's chemical industry.
With the development of the Chinese economy, the proportion of China’s exports in the world is increasing. Both OECD and China need to cooperate with and support each other. In terms of pesticides, the significance of China joining OECD is as follows:
1) Helps to introduce new pesticides from abroad.
2) Promotes the development of the pesticide industry in China
Promoting mutual acceptance of pesticide registration data will greatly promote the research and development of pesticides in large-scale Chinese pesticide enterprises, increase the registration of China's own brands abroad, thus promoting the transformation and upgrading of the industry and promoting the quality of pesticide export trade.
3) Increases China’s voice and participation in international standard
4) Improves the capability of the test system in China
We believe the cooperation between the Chinese government and OECD will further promote mutual acceptance of test data.
7. New Pesticide Registration Plan for Foreign Enterprises
A total of 21 new pesticides were registered by domestic enterprises under the New Registration Data Requirements during 2020 and 2021, among which there are 4 chemical pesticides and 17 biological pesticides.
Among the 4 new chemical pesticides, Quinotrione and Thiorantraniliprole are domestic innovative chemical pesticides in China, and Prothioconazole and Tembotrione are the registered pesticides with expired patents of Bayer. Many domestic enterprises have completed tests of Prothioconazole and Tembotrione and applied for registration according to the New Registration Data Requirements, but the registration approval rate is still very low.
At present, due to the MAD issue and the toxicology data requirements of major metabolites, new pesticide registrations for overseas enterprises may have been affected to a certain extent. There were only 6 new pesticides registered under the new Pesticide Registration Data Requirements during 2020 and 2021, including 5 chemical pesticides and 1 biogenic pesticide. Compared with the past, the number of new pesticide registrations significantly decreases, with a very low registration approval rate. However, China is an important market for overseas enterprises, while sales growth is impossible without new pesticide registration in China. Pesticides registered during 2020 and 2021 all become popular in the market, so it is still acceptable even with higher registration costs.
As the new pesticide registration is time consuming, overseas enterprises should consider how to make predictions about China's pesticide registration policy, fully understand China’s pesticide registration policy and make a good plan for the registration project to reduce risk. If they adopt a passive strategy in the Chinese market, it may lead to loss of the market and the preemptive registration by domestic manufacturers.
Overseas enterprises should focus on the following two issues at present:
1.For pesticides that applied for registration but did not get approval during 2020 and 2021, although many tests provide overseas GLP reports, there is a set of relatively complete registration data in accordance with Pesticide Registration Data Requirements. How to make a further plan for additional tests and registration? How to re-submit an application? These are challenges for overseas enterprises.
2.New pesticides should be registered in China according to the market demand. The establishment of a registration project, plan and test arrangement of new pesticides in China should be made based on the prediction of the Chinese policy.