China Pesticide Registration Hampered by Major Deficiency in Field Trial Application and Efficacy Study

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pesticide field trialAs a preliminary and essential step in registering a pesticide finished product in China, the applicant should obtain the field trial approval from the MoA. Efficacy and residue studies can be then performed in accordance with full registration requirements. The MoA Order 10 “Data Requirement on Pesticide Registration” was issued in 2008 to specify the requirement for each category of pesticide. The success rate of field trial application decreased from over 90% in 2007 to less than 70% in 2009. ICAMA has summarized the most common problem during field trail application and efficacy study to help applicants better understands data requirements.

Field Trial Application

General Requirement

Applicants are required to fill the “Application form of Field Trial for Pesticide Registration” including the following details:

Data Requirement for Field Trial Application

 

New Pesticide

New Formulation

Me-too Product

Novelty

containing on AI(active ingredient )which was not yet registered in China or the active ingredient was within the 6 years’ data protection period

containing on AI which was already registered in China, but differ from previously registered product in formulation type, AI composition (AI of single compound formulation or the combination and ratio of the AIs in multiple compound formulation) or content level

Formulation , AI combination/ratio and content level were identical to the product previously registered in China

Product Chemistry

Summary on the active ingredient, technical material and formulation;

Summary on the active ingredient and formulation

If the product contains active ingredient which was previously registered but under data protection in China, the applicant should provide the information as new pesticide;

If the formulation contains active ingredient which was registered but no longer data protected in China, the applicant should provide:

  • Product chemistry-summary on the active ingredient and formulation;
  • Summary on the acute oral; acute dermal; acute inhalation toxicity tests;
  • The registration number, registrant name, product name of the reference product and supporting document for the conclusion on equivalence determination;

If the product was neither applicable for item A nor item B, the applicant should file the application as new formulation. The data requirement would change slightly depend on the number of AIs.

Toxicology

Summary on toxicology profile of technical material and Formulation

Summary on the acute oral; acute dermal; acute inhalation toxicity tests;

First aid measures;

Efficacy

Mode of action, spectrum and analysis/prediction of unknown mechanism;

Report on the laboratorial bioactivity test;

Report on the laboratorial test for crop safety;

Trial crop, target, application method and precautions;

Trial crop, target, application method and precautions;

If the product is intended for new pests, the  laboratory bioactivity test report is required;

if the product is intended for new crop, the crop safety test report is required;

Explanation on the combination of the active ingredients and report of formulation screening(for multiple compound formulation);

Other Data

Efficacy, toxicology, residue, environmental impact and registration status in other country/region

If the new formulation only alters the formulation or content level of the previously registered product, the applicant should also explain the reason for the purpose;

If the multiple compound formulation is identical to the registered product in formulation type, AIs, usage and application method but only differ in AI ratio, an comparison analysis on the advantage and disadvantage is required;

Content Level

The content of each active ingredient and total content of the formulation should be established in integer values using standardized units. For plant growth regulator, botanical pesticide and public health insecticide are difficult to express as an integer, the applicant should provide an additional explanation for any deviation from this rule. Microbial pesticide will not be subject to such requirements. The content level of active ingredient should be represented as a percentage, except in cases where specific provisions have been made by the MoA and other industrial/national standards. In cases where products with same formulation type, AI composition or content level was previously registered and the content was expressed in “g/L”, the content of its subsequent proposed product can be expressed in “g/L”.

According to the MoA Announcement 946 and Announcement 1158, pesticide with same formulation type and AI composition (including multiple compound formulations under same AI ratio) can be registered at maximum of 5 content levels. The content of active ingredient in EC, ME and WP formulation should equal or be higher than the registered product. If the content level of a previously registered product is equal or greater than 10 %( 100g/L), the content interval between the subsequent proposed product should be equal or less than 5 %( 5g/L). If the content level of a previously registered product is equal or less than 10 %( 100g/L), the interval should not be greater than 50% of the content level of the previously registered product. The requirement on content levels of 47 single-based pesticides was further specified by MoA’ Announcement 1158. Products with content level cannot meet above requirements will be rejected.

Food Crop

The 8th session of the 18th National Pesticide Registration Committee has further regulated registration of pesticides designated for use on ornamental plant, non-crop land, turf, and forestry use: if a pesticide is usable for both food crop and aforementioned non-food crop, the product should be initially proposed for food crop use or both food crop and non-food crop use.

There are two special exceptions: if a pesticide containing glyphosate, glufosinate or diquat was used for non-crop land weed control, it can be registered for non-cropland use only; hexazinone, sulfometuron-methyl and trichlopyr are mainly for forestry use, and pesticide containing these active ingredients can be registered for forestry use only.

Laboratorial Bioactivity Test

If a single formulation containing new AI, or the AI is still under data protection, or the AI was firstly registered for the pest/disease, the laboratory report on bioactivity of the product should be required. China has continuously updated the guidelines for laboratorial bioactivity test for pesticide in the last decade. A total of 47 test methods are currently applicable for pesticide laboratory bioactivity study, including 15 for insecticide, 8 for herbicide, 18 for fungicide and 4 for plant growth regulator.

The test should be conducted by the MoA accredited facilities in accordance with the corresponding mechanism and target of the pesticide. If none of the guidelines are applicable to the product, the applicant can utilize other test method to demonstrate bioactivity but must also explain the rationale for this testing approach.

Generally, an existing registered product will serve as a control during testing and the tested product will be prepared into 5 to 7 solutions at different concentration levels to calculate the median effective concentration, median lethal concentration, and median effective dosage of the tested product. However, ICAMA found that the utilization of a control product and the concentration intervals are the most frequent mistakes made in the laboratory bioactivity test. The mode of action and mechanism of the control product should be similar to the tested product. For example, if the applicant is trying to register a botanical pesticide, a registered botanical product under the same pesticide category should be referenced as the control product instead of a conventional chemical pesticide. The concentration interval of the solutions should be geometrical or arithmetical and the calculated median effective dosage should be covered within the tested range. If bioactivity testing is not applicable for the product, the applicant may apply for the exemption by further explanation.

Report on Laboratorial Screening Test for Multiple Compound formulations

The laboratorial screening test report is required for new compound formulations (multiple active ingredients used), or the multiple compound formulation is under data protection, or the multiple compound formulation cannot be registered under equivalent product. 3 official guidelines can be utilized for the screening:

  • NY/T 1154.7-2006 Pesticides Guidelines for Laboratory Bioactivity Tests Part 7: Synergism Evaluation of Insecticide Mixtures;
  • NY/T 1155.7-2006 Pesticides Guidelines for Laboratory Bioactivity Tests Part 7: Synergism Evaluation of Herbicide Mixtures;
  • NY/T 1156.6-2006 Pesticides Guidelines for Laboratory Bioactivity Tests Part 6: Synergism Evaluation of Fungicide Mixtures;

The active ingredients are prepared into not less than 5 multiple compound formulations with different AI ratios, together with the single compound formulations of each active ingredient, each multiple compound formulation and single compound formulation were further diluted into 5 to 7 solutions at different concentration levels. The effective dosages of the compound formulation and the single compound formulations will be calculated and the latter will be utilized for calculating the theoretical effective dosage of the multiple compound formulation. By comparing the effective dosage and theoretical effective dosage of the compound formulation, the effect of the multiple compound formulations at different AI ratio will be determined: synergism, addition or antagonism and the optimal AI ratio can be predicted. ICAMA found that the applicant tested insufficient numbers of the compound formulation or the ratio of the proposed formulation is often beyond the study scope.

Report on the Laboratorial Test for the Safety on Host Crop

If a product containing new active ingredient or the active ingredient is under data protection, or the active ingredient is firstly registered on the crop, a laboratory test report on crop safety will be required. Depending on the product type and application method, the test should be conducted under following guidelines:

  • NY/T 1555.6-2006 Pesticide Guidelines for Laboratory Bioactivity Tests Part 6: Soil Application Test for Crop Safety of Herbicide;
  • NY/T 1155.8-2007 Pesticide Guidelines for Laboratory Bioassay of Pesticides Part8: Foliar Application Test for Herbicide Crop Safety Evaluation;
  • NY/T 1965.1-2010 Guidelines for Crop Safety Evaluation of Pesticide-Part 1: Laboratory Test for Crop Safety Evaluation of Fungicides and Insecticides;
  • NY/T 1965.2-2010 Guidelines for Crop Safety Evaluation of Pesticides Part 2: Laboratory Test for Crop Safety of Photosynthesis-Inhibiting Herbicides;
  • NY/T 1965.3-2013 Guidelines for Crop Safety Evaluation of Pesticides Part3: Laboratory Test for Crop Safety Evaluation of Seed Treatment Agents;

At least 3 varieties of the host crop should be tested and the maximum dosage of the proposed pesticide should be multiplied 1, 2 and 4 times to evaluate phytotoxicity to the host crop. However, most of the applicant tests less than 3 crop varieties or the minimum dosage was multiplied to demonstrate crop safety. Some of the report only contains the type of the crop damage and the original survey data was omitted. If the product was for a rare ornamental crop or the variety of the host crop is limited, applicants should provide additional explanations as to why the number of tested crop varieties was reduced. If the product is intended for fruit tree and forest tree, where the laboratorial study is not applicable, the crop safety evaluation test can be conducted in the field test.

Efficacy Data

Field Trial

After the approval for field trail, the efficacy/residual tests will be performed by the MoA accredited testing facilities. Generally, the efficacy studies are carried out at “plot trial” scale under following circumstances:

  • For insecticide and fungicide, a minimum of 2-years trial report in at least 4 provincial administrative areas is required;
  • For herbicide and plant growth regulator, a minimum of 2-years of trial report in at least 5 provincial administrative areas is required;
  • For long-residue herbicides, additional bio-safety test report of succession crops will be required;
  • For pesticide utilized under stable environment(such as storage, antisepsis and reservations purpose), a 2-cycle efficacy test report in 2 or more provincial administrative regions would suffice;
  • If the pesticide was for regional use( localize crop such as lax, sugar beets, sunflowers, ginseng, rubber trees, lychee trees, longan trees, bananas, mango trees, etc. or pests, weeds, and diseases limited to localized areas), same tests in at least 3 provincial administrative regions for a minimum of 2 years would suffice;
  • If the product was proposed under a new formulation registration category, the number of test sites and duration would be reduced;

More than one testing facility will be sponsored by the applicant during the efficacy trial stage. It is important during the trial that if a pesticide was applied by root irrigation at site A, likewise, it should be applied by root irrigation at site B rather than being sprayed at on the stem. ICAMA reports reveal that it is inconsistencies like this in the study plans between the different testing facilities that are a major source of problems for applicants. The applicant should determine a reasonable and practical dosage range for the product and ensure consistent study program among different testing facilities.

A previously registered product will serve as control during the study at each test site. The product should achieve positive control performance and possess similar mechanism with the tested product. If the reference product has been used for many years and the actual dosage has exceeded its registered dosage, the actual dosage should be utilized during the efficacy trial.

AI Combination in Multiple Compound formulations

Active ingredients are usually combined in multiple compound formulations to achieve a broader spectrum or reduce pest resistance. The purpose of the combination should be data supported and explained in a separate part of the registration dossier instead of being included in the “Report on Laboratorial Screening Test on Mixture” or other part of the application material. If the combination was designed for synergism, single compound formulations of its corresponding active ingredient should serve as control during the efficacy study and the efficacy of the multiple compound formulation should be shown to be higher than or comparable to the single compound formulation or the dosage of the active ingredient(s) of the multiple compound formulation should be lower than that of the single compound formulation. If the combination was of broader spectrum, it should be proposed for more pests than its single compound formulation.

In principle, combinations falls into below category would be rejected by ICAMA:

  • The active ingredients with similar mechanism, spectrum and mode of action, because the combination is unlikely to postpone the pest resistance, expand the target spectra or to have a synergism effect;
  • Insecticide and fungicide containing 3 or more active ingredients(except the seed treatment);
  • Herbicide and plant growth regulator are not permitted to be combined with active ingredient of other category;
  • Botanical pesticides are unsuitable to be mixed with chemical pesticide;

Reference Link

[AgroPedia] Chinese Pesticide Legislation Overview

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