Pesticides play an important role in preventing and controlling agricultural and forestry diseases, improving grain yield and improving grain quality, but the use of pesticides will inevitably bring negative effects on the quality and safety of agricultural products, human health and environmental safety. The International Code of Conduct for Pesticide Management, issued jointly by the Food and Agriculture Organization of the United Nations and the World Health Organization, requires national pesticide management authorities to establish a re-registration procedure to conduct regular review and evaluation of registered pesticide products. Ensure that new risks are identified in a timely manner and effective regulatory measures are taken.
At present, the European Union, the United States, Canada, Mexico, Australia, Japan, South Korea and Thailand have established post-registration risk monitoring and re-evaluation systems according to their own conditions.
Since the implementation of the pesticide registration system in 1982, the requirements for pesticide registration data have undergone three major revisions, and the technical requirements and standards for safety evaluation have been significantly improved, and the old pesticide products previously registered can no longer fully meet the current safety evaluation requirements. In recent years, through the integration of resources, project support and other measures, the Ministry of Agriculture and Rural Affairs has continuously increased the safety management of pesticide registration, and tracked and evaluated a number of highly toxic and high-risk pesticide varieties. For example, for the subsequent drug hazard risk of metsulfuron-methyl, the environmental risk of flubendiamide and the human health risk of paraquat, start a special study, and introduce prohibited management measures in a timely manner; Further phased out phorate, isofenphos-methyl, isocarbophos, ethoprophos, omethoate, carbofuran in 2022 and 2023 Eight highly toxic pesticides, such as methomyl and aldicarb, reduced the proportion of highly toxic pesticides to less than 1% of the total number of registered pesticides, effectively reducing the safety hazards of pesticide use.
Although China has gradually promoted and explored the use monitoring and safety evaluation of registered pesticides, it has not yet established systematic and targeted re-evaluation rules and regulations, and the re-evaluation work is insufficient, the process is not fixed, and the main responsibility is not clear, and there is still a big gap compared with developed countries. Therefore, learning from the mature model and experience of the European Union and the United States, making clear the implementation procedures and requirements of pesticide registration reevaluation in China, and building a new pesticide management model that integrates registration review, reevaluation and registration continuation is an important management content for comprehensively ensuring the safety of pesticide use and sustainable industrial development.
1 Reevaluate the project category
1.1 European Union
1.1.1 review program for old varieties
In 1993, the European Commission (referred to as the “European Commission”) in accordance with the provisions of Directive 91/414, nearly 1,000 pesticide active ingredients registered for use on the market before July 1993 were reassessed in four batches. In March 2009, the evaluation was basically completed, and about 250 active ingredients, or 26%, were re-registered because they met safety standards; 67% of the active ingredients withdrew from the market due to incomplete information, no enterprise application or enterprise initiative withdrawal. Another 70 or 7% of active ingredients were eliminated because they did not meet the requirements of the new safety evaluation.
1.1.2 review of approval
Article 21 of the new EU Pesticide Management Act 1107/2009 provides that the European Commission may at any time initiate a re-examination of registered active ingredients, that is, special re-evaluation. Requests for re-examination by Member States in the light of new scientific and technical findings and monitoring data should be taken into account by the Commission for initiating a special re-evaluation. If the Commission considers that an active ingredient may no longer meet the registration requirements, it will inform the Member States, the European Food Safety Authority (EFSA) and the manufacturing company of the situation and set a deadline for the company to submit a statement. The Commission may seek advice or scientific and technical assistance from the Member States and EFSA within three months from the date of receipt of the request for advice or technical assistance, and EFSA shall submit its opinion or the results of its work within three months from the date of receipt of the request. If it is concluded that an active ingredient no longer meets the registration requirements or that the requested further information has not been provided, the Commission will issue a decision to withdraw or amend the registration of the active ingredient in accordance with the regulatory procedure.
1.1.3 renewal of Registration
The continuation of the registration of pesticide products in the EU is equivalent to the periodic evaluation in China. In 1991, the EU promulgated the 91/414/EEC directive, which stipulates that the registration period of registered pesticide active ingredients cannot exceed 10 years, and it must apply for registration again when it expires, and can be renewed after meeting the registration standards. In 2009, the European Union promulgated a new pesticide regulation Law 1107/2009, replacing 91/414/EEC. The Act 1107/2009 stipulates that the active ingredients and preparations of pesticides must apply for registration renewal after expiration, and the specific time limit for the extension of active ingredients registration depends on its type and evaluation results: the extension period of active ingredients of pesticides is generally not more than 15 years; The duration of a candidate for substitution does not exceed 7 years; Active ingredients necessary for the control of serious plant pests and diseases that do not meet the current registration criteria, such as Class 1A or 1B carcinogens, Class 1A or 1B reproductive toxic substances, active ingredients with endocrine disrupting properties that may cause adverse effects on humans and non-target organisms, shall not be extended for more than 5 years.
1.2 United States
1.2.1 reregistration of old varieties
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended to require re-examination of active ingredients in pesticides registered before November 1, 1984. To ensure compliance with current scientific awareness and regulatory standards. In September 2008, the U.S. Environmental Protection Agency (EPA) completed the re-examination of 1,150 active ingredients (divided into 613 topics) through the Old Variety Re-registration Program, of which 384 topics were approved, or 63 percent. There were 229 topics on deregistration, accounting for 37 percent.
1.2.2 special review
Under FIFRA and the Code of Federal Regulations (CFR), a special reevaluation may be initiated when evidence indicates that a pesticide’s use meets one of the following conditions:
1) May cause severe acute injury to humans or livestock.
2) It may be carcinogenic, teratogenic, genotoxic, fetal toxic, reproductive toxic or chronic delayed toxic to humans.
3) The residue level in non-target organisms in the environment may be equal to or exceed the concentration of acute or chronic toxic effects, or it may have adverse effects on the reproduction of non-target organisms.
4) may pose a risk to the continued survival of an endangered or threatened species as designated by the Endangered Species Act.
5) May result in the destruction of important habitats of endangered or threatened species or other adverse changes.
6) There may be risks to humans or the environment, and it is necessary to determine whether the benefits of pesticide use can offset the negative social, economic and environmental effects.
Special reevaluation usually involves an in-depth evaluation of one or several potential risks, with the ultimate goal of reducing the risk of a pesticide by reviewing existing data, obtaining new information and/or conducting new tests, assessing the identified risks and determining appropriate risk reduction measures. After the special reevaluation is completed, EPA may initiate formal proceedings to revoke, deny, reclassify, or modify the registration of the product concerned. Since the 1970s, EPA has conducted special reevaluations of more than 100 pesticides and completed most of those reviews. Currently, several special reevaluations are pending: aldicarb, atrazine, propazine, simazine, and ethyleneoxide.
1.2.3 registration review
Given that the old variety reregistration program has been completed and the special reevaluation has taken many years, EPA has decided to initiate the reevaluation as a successor program to the old variety reregistration and special reevaluation. the current reevaluation of EPA is equivalent to the periodic evaluation in China, and its legal basis is the Food Quality Protection Act (FQPA), which proposed the periodic evaluation of pesticides for the first time in 1996, and amended the FIFRA. EPA is required to periodically review each registered pesticide at least once every 15 years to ensure that each registered pesticide remains in compliance with current standards as risk assessment levels evolve and policies change.
In 2007, FIFRA issued an amendment to formally initiate the reevaluation, requiring EPA to complete its review of 726 pesticides registered before October 1, 2007, by October 31, 2022. As part of the review decision, EPA must also fulfill its obligation under the Endangered Species Act to take early risk mitigation measures for endangered species. However, due to the COVID-19 pandemic, the delay in submitting data from applicants and the complexity of evaluation, the work was not completed on time. In 2023, the EPA issued a new 3-year reevaluation plan, which will update the reevaluation deadline for 726 pesticides registered before October 1, 2007, and 63 pesticides registered after that date to October 1, 2026. It is important to note that, regardless of whether a pesticide has been reevaluated, EPA will take appropriate regulatory action when it determines that the pesticide exposure poses an urgent risk to humans or the environment that requires immediate attention.
2 Related Procedures
As the EU old variety evaluation, the United States old variety re-registration and special reevaluation projects have been completed, at present, the EU mainly through the registration extension, the United States mainly through the reevaluation project to carry out the safety evaluation of registered pesticides, which is essentially equivalent to the periodic evaluation in China.
2.1 European Union
The continuation of registration in the EU is divided into two steps, the first is the continuation of the active ingredient registration. The active ingredient may be renewed if it is determined that one or more representative uses of the active ingredient and at least one preparation product containing the active ingredient meet the registration requirements. The Commission may combine similar active ingredients and establish priorities and work programmes based on their effects on human and animal health and environmental safety, taking into account, as far as possible, the need for effective control and resistance management of the target. The programme should include the following: procedures for the submission and evaluation of applications for registration renewal; Information that must be submitted, including measures to minimize animal testing, such as the use of intelligent testing strategies such as in vitro screening; Data submission deadline; New data submission rules; Evaluation and decision-making periods; And the allocation of the assessment of active ingredients to member States.
2.1.1 Active ingredients
Active ingredients enter the next renewal cycle 3 years before the end of the validity period of their registration certificate, and interested applicants for the renewal of registration (either the applicant at the time of the first approval or other applicants) should submit their application 3 years before the expiration of the registration certificate. The evaluation of the data on the continuation of the active ingredient registration is carried out jointly by the rapporteur member state (RMS) and the co-rapporteur member state (Co-RMS), with the participation of EFSA and other Member States. In accordance with the criteria set by the relevant regulations, guidelines and guidelines, each Member State designates the Member State with the necessary resources and capabilities (manpower, job saturation, etc.) as the presiding State. Due to a variety of factors, the presiding State and co-Presiding State of the reevaluation may be different from the State in which the designation was first registered. On 27 March 2021, Regulation 2020/1740 of the European Commission came into effect, setting out specific matters for the renewal of the registration of active ingredients for pesticides, applicable to active ingredients whose registration period is on or after 27 March 2024. For active ingredients that expire before March 27, 2024, Regulation 844/2012 will continue to apply. The specific process of registration renewal in the EU is as follows.
2.1.1.1 Pre-application Notification and feedback Suggestions
Prior to applying for renewal of registration, the enterprise shall first submit to EFSA a notice of the relevant trials that it intends to carry out in support of the renewal of registration, so that EFSA can provide it with comprehensive advice and conduct a public consultation to ensure that the relevant trials are carried out in a timely and reasonable manner. Businesses may seek advice from EFSA at any time before renewing their application. EFSA shall inform the presiding State and/or the co-Presiding State of the notification submitted by the enterprise and make a general recommendation based on the examination of all information relating to the active ingredient, including previous registration information or continuation of registration information. If several applicants simultaneously seek advice on the renewal of registration for the same component, EFSA shall advise them to submit a joint renewal application.
2.1.1.2 Application Submission and acceptance
The applicant shall submit the renewal application electronically within 3 years prior to the expiry of the active ingredient registration through the central submission system designated by the European Union, through which the presiding State, co-Presiding State, other Member States, EFSA and the Commission may be notified. The presiding State shall inform the applicant, the co-Presiding State, the Commission and EFSA, within one month of the submission of the application, of the date of receipt and the admissibility of the application for renewal. If one or more elements are missing in the submitted materials, especially if the complete test data is not submitted as required, the presiding country shall notify the applicant of the missing content within one month from the date of receipt of the application, and require the replacement within 14 days, if the missing materials are not submitted or no valid reasons are provided at the expiration, the renewal application will not be accepted. The presiding State shall promptly notify the applicant, the co-Presiding State, the Commission, the other Member States and EFSA of the decision and the reasons for its inadmissibility. Prior to the deadline for the continuation of the application, the co-presiding Country shall agree on all review tasks and workload allocation.
2.1.1.3 Data review
If the application for continuation is accepted, the presiding State will review the main information and seek public comments. EFSA shall, within 60 days from the date of publication of the continuation application, allow the public to submit written comments on the continuation application information and the existence of other relevant data or experiments. The presiding State and co-Presiding State then conduct an independent, objective and transparent assessment of whether the active ingredient still meets the requirements of the registration criteria, based on current scientific findings and applicable guidance documents, examining all information received on the renewal application, previously submitted registration data and evaluation conclusions (including previous draft evaluations) and written comments received during the public consultation. Information submitted by applicants beyond the scope of the request, or after the specified submission deadline, will not be considered. the presiding State shall submit a draft renewal assessment report (dRAR) to the Commission and EFSA within 13 months of the submission of the renewal request. During this period, the presiding State may request additional information from the applicant and set a time limit for the additional information, may also consult EFSA or request additional scientific and technical information from other Member States, but shall not cause the evaluation period to exceed the specified 13 months. The draft registration extension assessment report should contain the following specific elements:
1) Proposals for the continuation of registration, including any necessary conditions and restrictions.
2) Recommendations on whether the active ingredient should be considered a “low risk” active ingredient.
3) Recommendations on whether the active ingredient should be considered as a candidate for replacement.
4) Recommendations for the setting of maximum residue limit (MRL), or reasons for not involving MRL.
5) Recommendations for classification, confirmation or reclassification of active ingredients.
6) A determination of which trials in the registration continuation data are relevant to the evaluation.
7) Recommendations on which parts of the report should be consulted by experts.
8) Where relevant, the co-presiding State does not agree with the points of the assessment of the Presiding State, or the points on which there is no agreement among the Member States constituting the joint Panel of Presiding States.
9) The outcome of the public consultation and how it will be taken into account.
The presiding State should communicate promptly with the Chemicals regulatory authorities and, at the latest, submit a proposal to the European Chemicals Agency (ECHA) at the time of submission of the draft continuation assessment report to obtain at least the classification under the EU Classification, Labelling and Packaging Regulation for Substances and Mixtures. The active ingredient is explosive, acute toxicity, skin corrosion/irritation, severe eye injury/irritation, respiratory or skin allergy, germ cell mutagenicity, carcinogenicity, reproductive toxicity, specific target organ toxicity from single and repeated exposure, and a uniform classification of hazards to the aquatic environment. The trial State shall adequately state the reasons why the active ingredient does not meet the classification criteria for one or more of the hazard classes, and ECHA may comment on the views of the trial State.
2.1.1.4 Comments on the draft continuation assessment report
EFSA shall review whether the draft continuation assessment report contains all relevant information and circulate it to the applicant and other Member States no later than 3 months after receipt of the report. Upon receipt of the draft continuation assessment report, the applicant may, within two weeks, request EFSA to keep certain of the information confidential, and EFSA shall make the draft continuation assessment report public, except for the duly confidential information accepted, together with the updated continuation application information. EFSA will allow the public to submit written comments within 60 days from the date of publication of the draft continuing assessment report and to send them, together with their own comments, to the presiding State, the co-presiding State or the group of Member States co-presiding.
2.1.1.5 Peer review and resolution issuance
EFSA organizes experts (experts of the presiding country and experts of other member states) to conduct peer review, discuss the review opinions of the presiding country and other outstanding issues, form preliminary conclusions and public consultation, and finally submit the conclusions and resolutions to the European Commission for approval and release. If, for reasons beyond the control of the applicant, the evaluation of the active ingredient has not been completed before the expiry date, the EU will issue a decision to extend the validity of the active ingredient registration to ensure that the registration renewal is completed smoothly.
2.1.2 Preparations
The holder of the relevant registration certificate shall, within 3 months of the renewal of the registration of the active ingredient, submit an application for the renewal of the registration of the pharmaceutical product to the Member State that has obtained the registration of the corresponding pharmaceutical product. If the registration holder applies for the renewal of the registration of the same pharmaceutical product in different regions, all the application information shall be communicated to all Member States in order to facilitate the exchange of information between Member States. In order to avoid duplicate tests, the applicant shall, before conducting tests or tests, check whether other enterprises have obtained the same preparation product registration, and shall take all reasonable measures in a fair and transparent manner to reach a test and test report sharing agreement.
In order to create a coordinated and efficient operation system, the EU implements a regional registration system for preparations, which is divided into three regions: North, central and South. the zonal Steering Committee (zonal SC) or its representative member States will ask all relevant product registration certificate holders whether to apply for renewal of registration and in which region, It also determines the zonal rapporteur Member State (zonal RMS). In order to plan ahead, the regional presiding State should be appointed well in advance of the submission of the application for continuation of the drug product, which is generally recommended to be done before EFSA publishes the conclusions of the active ingredient review. It is the responsibility of the regional presiding State to confirm the number of applicants who have submitted renewal applications, to inform the applicants of the decision and to complete the assessment on behalf of the other States in the region (continuation assessment for certain uses of pharmaceutical products is sometimes done by a Member State without the use of a zonal registration system). The active ingredient review country is required to complete the comparison of the active ingredient continuation data with the drug product continuation data. The regional presiding State shall complete the evaluation of the continuation data of the preparation within 6 months and send it to Member States and applicants for comments. Each Member State shall complete the continued approval of its respective formulation products within three months. The entire formulation renewal process needs to be completed within 12 months of the end of the active ingredient registration renewal.
2.2 United States
In the reevaluation process, the U.S. EPA is required to conduct a risk assessment, determine whether the pesticide meets the FIFRA registration criteria, and issue a review decision. EPA’s pesticide regulatory Agency consists of seven divisions, four regulatory divisions, and three specialized divisions. The Registry and Reevaluation Service is the regulatory Branch, and the Registry is responsible for new applications, uses and changes in all conventional chemical pesticides; The Reevaluation Service is responsible for post-registration evaluation of conventional pesticides. The Health Effects Branch, the Environmental Behaviour and Effects Branch and the Biological and Economic Analysis Branch, which are specialized units, are primarily responsible for the technical review of all relevant data for pesticide registration and post-registration evaluation, and for the completion of risk assessments.
2.2.1 Thematic division
A reevaluation topic consists of one or more active ingredients and all products containing those active ingredients. When the chemical structure and toxicological characteristics of different active ingredients are closely related, and part or all of the data required for hazard assessment can be shared, they can be grouped into the same topic; Pesticide products containing multiple active ingredients are also subject to the reevaluation topic for each active ingredient. When new data or information becomes available, EPA may also make changes to the reevaluation topic. If it finds that multiple active ingredients in a topic are not similar, EPA may split the topic into two or more independent topics, or it may add or remove active ingredients from the reevaluation topic.
2.2.2 Formulation of schedule
Each reevaluation topic has a base date, which is either the first registration date or the re-registration date of the pesticide product first registered in the topic (the re-registration date refers to the date on which the re-registration decision or interim decision was signed), generally whichever is later. EPA typically bases its current reevaluation schedule on the baseline date or the most recent reevaluation, but may also review multiple relevant topics simultaneously for efficiency. EPA will post the reevaluation file, including the baseline date, on its website and retain the reevaluation schedule for the year in which it was published and for at least two subsequent years thereafter.
2.2.3 Reevaluation starts
2.2.3.1 opening the docket
EPA initiates the reevaluation by creating a public dossier for each pesticide reevaluation topic and soliciting comments. However, if EPA determines that a pesticide meets the criteria for FIFRA registration and no further review is required, it can skip this step and announce its final decision directly through the Federal Register. Each case file will remain open throughout the reevaluation process until a final decision is made. The file includes, but is not limited to, the following: an overview of the status of the reevaluation project; A list of existing registrations and registrants, any Federal Register notice regarding pending registrations, existing or tentative residual limits; Risk assessment documents; A bibliography of the current register; Accident data summary; And any other relevant data or information. The file also includes a preliminary work plan that includes basic information EPA currently has about the pesticide to be controlled and how it will be used, as well as a projected risk assessment, data needs, and review schedule.
2.2.3.2 Public comment
EPA publishes a notice in the Federal Register for public comment on the reevaluation file and preliminary work plan for a period of not less than 60 days. During this time, stakeholders can ask questions, make suggestions or provide relevant information. The submission of such information must meet the following requirements.
1) The relevant information must be submitted within the specified comment period, but EPA will also consider, at its discretion, whether to adopt data or information submitted thereafter.
2) Information must be submitted in a readable and usable form. For example, any material not in English must be accompanied by an English translation, and any information submitted in audio or video form must be accompanied by a written record. Written submissions may be submitted in paper or electronic form.
3) The submitter must clearly identify the source of the submitted data or information.
4) The subfiler may request that EPA re-examine the information rejected in the previous review, but must explain the reasons for the re-review.
Based on information received during the comment period and prior review, EPA develops and issues a final work plan that includes the data requirements for the plan, comments received, and a summary of EPA’s responses.
If a pesticide active ingredient does not have any product registration, or all registered products are withdrawn, EPA will no longer evaluate the pesticide.
2.2.3.3 Stakeholder participation
To increase transparency and engagement and address uncertainties that may affect pesticide risk assessment and risk management decisions, such as unclear labeling or missing trial data, EPA may conduct focusmeetings with stakeholders on upcoming or ongoing reevaluation topics. Having sufficient information early on can help EPA narrow its evaluation to areas that really need attention. For example, prior to the commencement of the reevaluation, EPA may consult with the registration certificate holder or pesticide user about the usage and use of the product, and during the reevaluation, EPA may consult with the registration certificate holder, pesticide user or other relevant personnel to jointly develop a pesticide risk management plan.
2.2.4 Re-evaluation and implementation
2.2.4.1 Assess the changes that have occurred since the last review
EPA will evaluate any changes in regulations, policies, risk assessment process approaches, or data requirements that have occurred since the last registration review, determine the significance of those changes, and determine whether the reevaluated pesticide still meets the FIFRA registration criteria. At the same time, review all relevant new data or information to determine whether a new risk assessment or a new risk/benefit assessment is necessary.
2.2.4.2 Conduct new assessments as needed
If it is determined that a new assessment is necessary and the existing assessment data is sufficient, EPA will directly re-conduct the risk assessment or risk/benefit assessment. If the existing data or information does not meet the new assessment requirements, EPA will issue a data call notice to the relevant registration certificate holder in accordance with the relevant FIFRA regulations. The registration certificate holder is usually required to respond within 90 days to agree with the EPA on the information to be submitted and the time to complete the plan.
2.2.4.3 Assessment of impacts on endangered species
When EPA reevaluates a pesticide active ingredient in a reevaluation, it is obligated to comply with the provisions of the Endangered Species Act to avoid harm to federally listed threatened or endangered species and adverse impacts on designated critical habitat. If necessary, EPA will consult with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service.
2.2.4.4 Public participation
If a new risk assessment is conducted, EPA will typically publish a notice in the Federal Register providing a draft risk assessment for public review and comment, with a comment period of at least 30 days and usually 60 days. EPA will also post the revised risk assessment report in the Federal Register, an explanation of any changes to the proposed document, and a response to the public comment. If the revised risk assessment indicates that there are risks of concern, a comment period of at least 30 days may be provided to allow the public to submit further suggestions for risk mitigation measures. If the initial screening indicates a low level of pesticide use/utilization, low impact to stakeholders or the public, low risk, and little or no risk reduction action is required, EPA may not conduct a separate public comment on the draft risk assessment, but instead make the draft available for public review along with the reevaluation decision.
2.2.5 registration review decision
The reevaluation decision is the EPA’s determination of whether a pesticide meets the statutory registration criteria, that is, it examines factors such as the product’s label, active ingredients and packaging to determine whether the pesticide will perform its intended function without causing unreasonable adverse effects on human health or the environment.
2.2.5.1 proposed registration review decision or proposed interim decision
If EPA finds that a new risk assessment is not necessary, it will issue a proposed reevaluation decision under the regulations (the “Proposed Decision”); When additional assessments, such as an endangered species assessment or endocrine screening, are required, a proposed interim decision may be issued. The proposed decision will be published through the Federal Register and will be available to the public for a comment period of at least 60 days. The proposed decision mainly includes the following elements:
1) State its proposed conclusions on the criteria for FIFRA registration, including the findings of the formal Endangered Species Act consultation, and indicate the basis for these proposed conclusions.
2) Identify the proposed risk mitigation measures or other necessary remedies and justify them.
3) Indicate whether supplementary data is needed; If required, state the data requirements and notify the registration card holder of the data call.
4) Specify any proposed label changes.
5) Set a deadline for completing each required action.
2.2.5.2 interim registration review decision
After considering all comments on the proposed interim decision, EPA may, at its discretion, issue an interim decision through the Federal Register prior to completion of the reevaluation. The interim decision includes an explanation of any changes to the previous proposed interim decision and a response to significant comments, and the interim decision may also: require new risk mitigation measures or implement interim risk mitigation measures; Request submission of updated labels; Clarify the data information needed to complete the evaluation and the submission schedule (data call notifications can be issued before, at the same time or after the interim reevaluation decision is issued). If the registration certificate holder fails to cooperate with the actions required in the interim reevaluation decision, EPA may take appropriate legal action.
2.2.5.3 final decision
EPA will issue a final decision upon completion of all assessments of the reevaluation, including, where appropriate, the assessment and consultation of species listed on the Federal Endangered and Threatened Wildlife List, as well as the review of endocrine disruptor screening programs. If the registration certificate holder fails to cooperate with the actions required in the reevaluation decision, EPA may take appropriate legal action under FIFRA.
3 Register a continuation request
3.1 European Union
The renewal of the EU registration of active ingredients for pesticides is a comprehensive assessment that combines old and new data, and applicants must submit complete data as required.
3.1.1 Active ingredients
Article 6 of Regulation 2020/1740 on renewal of registration specifies the information to be submitted for renewal of active ingredient registration, including:
1) The name and address of the applicant who is responsible for continuing the application and fulfilling the obligations stipulated by the regulations.
2) The name and address of the joint applicant and the name of the producer association.
3) A representative method of use of at least one plant protection product containing the active ingredient on a widely grown crop in each region, and proof that the product meets the registration criteria set out in Article 4 of Regulation No. 1107/2009.
The above “Method of use” includes the method of registration and evaluation in the continuation of registration. At least one of the plant protection products with the above representative methods of use should be free of other active ingredients. If the information submitted by the applicant does not cover all the areas involved, or is not widely grown in the area, the reason should be given.
4) necessary data and risk assessment results, including: i) indicating changes in legal and regulatory requirements since the approval of the active ingredient registration or the renewal of the most recent registration; ii) indicate changes in science and technology since the approval of the active ingredient registration or the renewal of the most recent registration; iii) indicate a change in representative use; iv) indicates that the registration continues to change from the original registration.
(5) the full text of each trial or study report and its abstract as part of the original registration information or subsequent registration continuation information in accordance with the active ingredient information requirements.
6) the full text of each trial or study report and its abstract as part of the original registration data or subsequent registration data, in accordance with the drug preparation data requirements.
7) Documentary evidence that it is necessary to use an active ingredient that does not meet current registration standards to control a serious plant pest.
8) For the conclusion of each test or study involving vertebrates, state the measures taken to avoid testing on vertebrates. The registration extension information shall not contain any test report of the intentional use of the active ingredient to humans or the use of a product containing the active ingredient.
9) A copy of the application for MRLS submitted in accordance with Article 7 of Regulation (EC) No 396/2005 of the European Parliament and of the Council.
10) A proposal for the classification or reclassification of the active ingredient in accordance with Regulation 1272/2008.
11) A list of materials that can prove the completeness of the continuation application, and mark the new data submitted at this time.
12) In accordance with Article 8 (5) of Regulation No. 1107/2009, the summary and results of the peer-reviewed public scientific literature.
13) Evaluate all information submitted according to the current state of science and technology, including the re-evaluation of some of the original registration data or subsequent registration continuation data.
14) Consideration and recommendation of any necessary and appropriate risk mitigation measures.
15) In accordance with Article 32b of Regulation 178/2002, EFSA may commission the necessary scientific tests to be carried out by an independent scientific research institute and communicate the results of the tests to the European Parliament, the Commission and the Member States. Such mandates are open and transparent, and all information relevant to the trial notification should be included in the registration extension application.
If the original registration data still meet the current data requirements and evaluation standards, it can continue to be used for this registration extension, but it needs to be submitted again. The applicant should use his or her best efforts to obtain and provide the original registration information or the relevant information as a continuation of subsequent registration. If the applicant for the renewal of registration is not the applicant for the initial registration of the active ingredient (that is, the applicant does not have the information submitted for the first time), it is necessary to obtain the right to use the existing registration information of the active ingredient through the applicant for the first registration or the administrative department of the evaluation country. If the applicant for renewal of registration provides evidence that the relevant information is not available, the presiding State or EFSA that conducted the previous and/or subsequent renewal review shall endeavour to provide such information.
If the previous registration data does not meet the current requirements, new tests and new reports need to be carried out. The applicant should identify and list the new tests to be carried out and their timetable, including a separate list of new tests for all vertebrates, taking into account the feedback provided by EFSA prior to the renewal of the application. The new test report should be clearly marked, explaining the reason and necessity. In order to ensure openness and transparency and reduce duplication of tests, new tests should be filed with EFSA before starting, and unfiled tests will not be accepted. The applicant may submit an application for data protection and submit both confidential and non-confidential versions of this data.
3.1.2 Preparations
Continuation of registration of pharmaceutical products is based on the active ingredients that have been completed. In accordance with Article 43 (2) of Regulation No. 1107/2009, applications for continuation of preparations shall include:
1) Copy of preparation registration certificate.
2) any new data required as of the time of application due to changes in information requirements, guidelines and their criteria (i.e., changes in active component test endpoints resulting from continued evaluation of registration).
3) Reasons for submitting new data: the new information requirements, guidelines and standards were not in force at the time of registration of the product; Or to modify the conditions of use of the product.
4) To certify that the product meets the registration renewal requirements of active ingredients in the regulations (including relevant restrictions).
5) If the product has been monitored, the monitoring information report shall be provided.
6) Where necessary, information for comparative assessment shall be submitted in accordance with relevant guidelines.
3.1.2.1 Data matching of active ingredients
When applying for the continuation of registration of pharmaceutical products, the applicant shall, according to the evaluation conclusion of the active ingredient, provide new information of each active ingredient that needs to be updated due to changes in data requirements and standards, modify and improve the corresponding pharmaceutical product data, and conduct risk assessment in accordance with the new guidelines and end values to ensure that the risk is still in an acceptable range. The matching of active ingredient data is usually the responsibility of the presiding country undertaking the ongoing review of the active ingredient registration. The applicant may provide the relevant active ingredient information to the designated lead Country by providing a declaration that the active ingredient information is in a non-protective period, proof of the right to use the information, a declaration that the preparation is exempt from submitting an active ingredient information, or by proposing to repeat the test. Approval of application information for continuation of registration of preparations can only rely on the same original drug that meets the new standard, and when the quality of the identified same original drug changes (including the maximum content of impurities), the applicant can provide reasonable arguments that the original drug used can still be regarded as equivalent.
3.1.2.2 Changes to good agricultural practices (GAP)
The applicant should provide a list of intended uses of the product, including a statement indicating that there has been no significant change in GAP in the area from the time of registration, and a separate list of secondary uses in the GAP form in the prescribed format. Only significant changes in GAP that are necessary to comply with changes in the active component assessment (new end values, adoption of new guidelines, conditions or restrictions in the registration renewal regulations) are acceptable, provided that the applicant submits all necessary supporting information. In principle, no significant dosage form changes can occur in the continuation application
3.1.2.3 Drug efficacy data
For efficacy, the applicant should determine and justify the submission of new test data. If the GAP change is triggered by a new end value, new guidelines, efficacy trial data for the new GAP should be submitted, otherwise, only resistance data should be submitted for the continuation application.
3.2 United States
The U.S. EPA’s data requirements for pesticide reevaluation are consistent with pesticide registration, registration changes, and re-registration, and there are no separate regulations. Targeted requests for information based on risk assessment needs in the reevaluation, feedback received during the public consultation, etc., will be published in the form of a final work plan and data call notice.
4 Other Issues
4.1 Joint Application
4.1.1 European Union
In accordance with Article 5, Chapter 3 of Regulation 2020/1740, if more than one applicant applies for the renewal of the registration of the same active ingredient, all applicants shall take all reasonable steps to submit information jointly. The association designated by the applicant may make the joint application on behalf of the applicant, and all potential applicants may be contacted with a proposal for joint submission of information.
Applicants can also submit complete information separately, but should explain the reasons in the information. However, in accordance with Article 62 of Regulation 1107/2009, repeated tests on vertebrates are not acceptable, so potential applicants and holders of relevant authorisation data should make every effort to ensure that the results of the vertebrate tests and studies involved are shared. For renewal of active ingredient registration involving multiple applicants, all data should be reviewed together, and conclusions and reports should be formed after comprehensive analysis.
4.1.2 United States
EPA recommends that applicants share reevaluation data, but there is no mandatory requirement. According to the data call notice, the holder of the registration certificate of the active ingredient of a pesticide can decide whether to jointly provide data with other applicants, conduct separate studies, or withdraw the registration. If separate trials by different applicants result in two different end points, EPA will use the most conservative end point.
4.2 Relationship between registration renewal and new registration
4.2.1 European Union
Prior to the commencement of the renewal of active ingredient registration, that is, before the Member State receives the renewal of active ingredient registration application, the applicant may continue to submit the application for registration of the relevant pharmaceutical product to the Member State (region); After the commencement of the renewal of active ingredient registration, the applicant can no longer submit the application for registration of the corresponding preparation to the Member State, and must wait for the issuance of the resolution on the renewal of active ingredient registration before submitting it in accordance with the new requirements.
4.2.2 United States
If an additional registration (e.g., a new dosage preparation) does not trigger a new risk assessment, EPA may accept the additional registration during the reevaluation period; However, if a new registration (such as a new scope of use) may trigger a new risk assessment, EPA may either include the product in the reassessment risk assessment or conduct a separate risk assessment of the product and use the results in the reassessment. The flexibility of the EPA is due to the fact that the three specialized divisions of the Health Effects Branch, the Environmental Behavior and Effects Branch, and the Biological and Economic Analysis Branch support the work of the Registry and the Reevaluation Branch, and can see all the data of the registry and the reevaluation simultaneously. For example, when the reevaluation has made a decision to modify the label, but it has not yet been issued, if a company submits an application for a label change, the registry will process it according to the reevaluation decision. This flexible approach allows EPA to better integrate resources and help companies get registered earlier.
4.3 Data Protection
4.3.1 European Union
The protection period for new active ingredient data and preparation data used for registration renewal is 30 months, starting from the date when the corresponding preparation product is first registered for renewal in each Member State, the specific date varies slightly from one Member State to another.
4.3.2 United States
Newly submitted reevaluation data has a data protection period of 15 years from the date of submission, and when an applicant refers to data submitted by another enterprise, it must usually prove that compensation has been provided to the data owner or permission has been obtained. If the active drug registration enterprise determines that it has submitted the required data for re-evaluation, the preparation product produced using the active drug has obtained the permission to use the data of the active drug, so it can retain the registration directly according to the reevaluation conclusion of the active drug, without adding additional information, but it still needs to take risk control measures such as modifying the label as required.
5. Summary and prospect
Overall, the EU and the US have the same objective in conducting reevaluations of registered pesticide products: to ensure that as risk assessment capabilities develop and policies change, all registered pesticides can continue to be used safely and do not pose an unreasonable risk to human health and the environment. However, there are some differences in the specific procedures. First, it is reflected in the connection between technology evaluation and management decision-making. The EU registration extension covers both technical assessment and final management decisions; The reevaluation in the United States only makes technical evaluation conclusions such as modifying labels and submitting new data, and the registration certificate holder needs to take the initiative to act in accordance with the conclusion and make corresponding applications to implement management decisions. Second, implementation methods are different. The extension of registration in the EU is divided into two steps. The first step is the extension of the active ingredient registration at the EU level. After the extension of the active ingredient registration is passed, the extension of the registration of pharmaceutical products is carried out in the corresponding member states. The reevaluation of active ingredients and formulation products in the United States is carried out simultaneously.
Registration approval and re-evaluation after registration are two important aspects to ensure the safety of pesticide use. In May 1997, China promulgated the “Regulations on Pesticide Management”, and after more than 20 years of development, a complete pesticide registration system and evaluation standard system have been established. At present, China has registered more than 700 pesticide varieties and more than 40,000 preparation products, more than half of which have been registered for more than 20 years. Long-term, extensive and large amounts of pesticide use will inevitably lead to the rise of biological resistance of the target, the increase of environmental accumulation, and the increase of human and animal safety risks. Re-evaluation after registration is an effective means to reduce the long-term risk of pesticide use and realize the whole life cycle management of pesticides, and is a beneficial supplement to the registration and approval system. However, China’s pesticide re-evaluation work started late, and the “Measures for the Management of Pesticide Registration” promulgated in 2017 pointed out for the first time from the regulatory level that the pesticide varieties registered for more than 15 years should be organized to carry out periodic evaluation according to the production and use situation and industrial policy changes. NY/ T2948-2016 “Technical Specification for Pesticide Reevaluation” issued in 2016 provides the basic principles and evaluation procedures for the reevaluation of registered pesticide varieties, and defines relevant terms, but its enforcement is limited as a recommended standard. In connection with the practical work of pesticide management in China, the research and analysis of the reevaluation system of the EU and the United States can give us the following thoughts and enlightenment.
First, give full play to the main responsibility of the registration certificate holder in the re-evaluation of registered pesticides. The general process of pesticide reevaluation in the EU and the United States is that the registration management department develops a work plan, puts forward the reevaluation varieties and concerns about risk points, and the holder of the pesticide registration certificate submits the information as required within the specified time. China can draw lessons from the actual situation, change the thinking of the pesticide registration management department to carry out verification tests and complete the overall work of pesticide reevaluation, further clarify the main responsibility of the holder of pesticide registration certificate in carrying out reevaluation and ensuring product safety, and improve the implementation methods of pesticide reevaluation in China.
The second is the establishment of pesticide reevaluation data protection system. The Regulations on Pesticide Management and its supporting rules clearly define the protection system of new pesticide varieties in China and the authorization requirements for pesticide registration data, but the reevaluation data protection and data authorization requirements are not clear. Therefore, the holders of pesticide registration certificates should be encouraged to actively participate in the reevaluation work, and the reevaluation data protection system should be clearly defined, so that the original data owners can provide data to other applicants for compensation, reduce repeated tests, and reduce the burden on enterprises.
The third is to build a post-registration evaluation system of pesticide risk monitoring, re-evaluation and registration continuation. In 2022, the Ministry of Agriculture and Rural Affairs newly issued the “Regulations on the Management of Pesticide Risk Monitoring and Evaluation (Draft for Comment)”, indicating China’s determination to systematically deploy and routinely carry out post-registration management of pesticides. In the future, we should also think positively, conduct extensive research, and learn from many aspects, and gradually establish and improve a post-registration safety management system for pesticides that is in line with China’s national conditions through the monitoring, re-evaluation and registration of pesticide use risk, so as to truly reduce all kinds of safety risks that may be caused by pesticide use, and effectively protect agricultural production, public health and environmental safety.
Post time: May-27-2024