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Chemicals Regulation Directorate

Data Requirements Handbook

26/11/2010 Chapter 8 - 1 Efficacy

CHAPTER 8: GUIDANCE ON EFFICACY REQUIREMENTS

CONTENTS

Section Page

1 Introduction 2 1.1 Efficacy requirements 2 1.2 Meeting efficacy requirements 2 1.3 Contact information 3

2 Scope of Efficacy Requirements 4 2.1 Legislative basis 4 2.2 Areas to be addressed under PPPR 4 2.3 Differences in areas addressed under COPR 7

3 Meeting Efficacy Requirements 8 3.1 Introduction 8 3.2 Presentation of efficacy information 9 3.3 Levels of control expected to be demonstrated 10 3.4 Overseas evidence 12 3.5 Extrapolation 14 3.6 Public domain evidence 15 3.7 Data owned by others 16 3.8 Experimental Data 16 3.9 Conducting field trials 18

4 Situation-Specific Guidance on Meeting Efficacy Requirements 25 4.1 Extrapolation between glasshouse or growth room tests and outdoor use 25 4.2 Biological Control Agents and pheromones 25 4.3 Comparability of pesticide formulations 26 4.4 Guidance on extrapolation in specific situations 32 4.5 Numbers of trials required for major crops. 36 4.6 Pest populations required in trials 36 4.7 Information required in support of peripheral label claims 38

5 Efficacy Guidelines 42




1. Introduction

The intrinsic biological activity of pesticides poses the potential for risks to operators, consumers and the environment. Whilst methods are available to reduce exposure and thus, reduce any risks (e.g. the use of protective clothing), no risk, however small, can be considered acceptable unless there is a proven benefit from the use of the pesticide. The main purpose of the efficacy consideration is to ensure that when a pesticide is used as recommended on the label, a consistent benefit will be achieved.

These guidance notes are intended to provide an outline of the efficacy requirements for approval and how these may be met. It is impracticable to set rigid guidelines for all types of pesticides, thus the information given is intended only as guidance, and the Environment Branch of CRD is always willing to discuss individual situations with applicants in more detail where necessary.

1.1. Efficacy requirements

The areas that need to be addressed in an efficacy submission are broadly comparable for COPR and PPPR but with some changes of emphasis and a few additions in the more recent legislation. If you are applying to register a pesticide you will need to have done the following.

lxviii) Provided evidence to support all the claims for control that you have included on the label.

lxix) Demonstrated that the product is safe to the crops on which you recommend its use.

lxx) Demonstrated an acceptable level of safety to adjacent and following crops.

lxxi) Supported all peripheral claims such as rainfastness, use of mixtures, safety to beneficial insects etc.

In some cases you may also be required to

lxxii) Consider and address the risk of resistance developing to an active substance.

lxxiii) Justify the dose you propose to specify on the label.

1.2. Meeting efficacy requirements

The information we require you to provide may come from a range of sources, detailed below, and must be presented in a suitable format, either as an efficacy overview (for COPR applications only) or preferably as a Biological Assessment Dossier (BAD). OECD format dossiers are also acceptable, provided all Annex III efficacy requirements are addressed and the data summarised in an appropriate format (see 3.2). In all cases you are advised to read the relevant detailed guidelines that follow.

http://www.pesticides.gov.uk/Migrated-Resources/Documents/G/g102.pdf







Table 8.1: Sources of information to meet efficacy requirements.

Extrapolation Provided a sound database is available it may be possible to extrapolate information from one target or crop to another closely related one, between different cropping situations or between closely related formulations.

Public Domain Evidence

Suitable information in published papers and books, including the Weed Control Handbook.

Data owned by others

Where data are protected they may be used if a suitable letter of access is provided by the owner. Where confidential data are no longer protected they may be used to support an application but remain confidential.

Trials data A programme of trials can be used to generate data specific to a given product application. Trials can be conducted in the UK or overseas though for the latter you should provide an acceptable case detailing why they are applicable to UK conditions. If you are planning to conduct trials please ensure you are familiar with any relevant guidance, such as EPPO guidelines.

Please note that most efficacy data generated in the UK since 1998 must have been produced by an Officially Recognised organisation. Other dates apply for elsewhere in the EU. Further details are in section 3.8.1.

1.3. Contact information

Should you have any query relating to efficacy, please use one of the following contact addresses:

Environment Branch Tel: 01904 455775 CRD Mallard House Fax: 01904 455711 Kings Pool 3 Peasholme Green Email: [email protected] York YO1 7PX

mailto:[email protected]




2. Scope of Efficacy Requirements

2.1. Legislative basis

The efficacy requirements for the registration of pesticides in the UK are defined in the Control of Pesticides Regulations 1986 (COPR), as amended and the Plant Protection Products Regulations 1995 (PPPR) as amended.

Under COPR pesticides can only be approved when Ministers are satisfied that they can be used safely and effectively. CRD's requirements for approval were previously outlined in the Registration Handbook and separate efficacy guidelines.

The PPPR implement the EC Council Directive 91/414/EEC which lays down specific requirements for the information necessary for evaluating efficacy. These are detailed below.

COPR will continue until all existing EC active substances are reviewed and placed on Annex I (positive list). PPPR will apply to new active substances coming onto the UK market and existing EC reviewed active substances that obtain Annex I listing.

2.2. Areas to be addressed under PPPR

Under PPPR the data supplied must be sufficient to permit an evaluation of the plant protection product covering the areas laid down in Directive 91/414 and subsequent Directives such as 93/71, see The Applicant Guide for full details. In particular it must be possible to evaluate the benefits that accrue from the use of a product, where possible in comparison to suitable reference products and damage thresholds, and to define its conditions of use.

Sufficient data must be supplied to CRD to confirm that the directions for use are applicable over all the conditions likely to be encountered when used according to the label recommendations, including for example regional and seasonal differences. All the following areas must be addressed for a new active substance. Specific products may be able to use information already supplied to support other products containing the same active substance.

2.2.1. Preliminary tests

Summaries of preliminary tests, including glasshouse and field studies, used to assess the biological activity of the product, must be submitted when requested by CRD. Where this information is not submitted a justification which is acceptable to CRD should be provided.

2.2.2. Dose justification

In order to clarify the dose response, doses lower than that recommended should be included in some trials in order to enable an assessment of the minimum dose necessary to achieve the desired effect.

http://www.pesticides.gov.uk/guidance/industries/pesticides/topics/pesticide-approvals/pesticides-registration/applicant-guide/the-applicant-guide-general-information-on-competion-of-the-application-overview




2.2.3. Effectiveness

Sufficient data should be provided to permit an evaluation of the level, duration and consistency of control or protection or other intended effects of the plant protection product, where possible, in comparison to suitable reference products.

Evidence should be submitted to show that the dose, timing and method of application recommended give adequate control, protection or have the intended effect in the range of circumstances likely to be encountered in practical use.

2.2.4. Crop Safety

The safety of a product to the main cultivars of the main crops for which it is recommended should be demonstrated, including examination of the effects of crop growth stage, vigour, and other factors which may influence susceptibility to damage or injury. Effects on yield should also be determined where relevant. When treated products are likely to be stored, the effect on the yield after storage, including data on storage life should, be determined where relevant.

For herbicides, and for other plant protection products for which adverse effects, however transitory, are seen during trials, the margins of selectivity on target crops should be established, using twice the recommended dose.

Where adverse effects occur, but are claimed to be unimportant in comparison with the benefits of use or because they are transient in nature, evidence to support this claim is required. For herbicides and where necessary for other products measurements of yield and quality should be submitted.

2.2.5. Resistance

Laboratory data and where it exists, field information relating to the occurrence and development of resistance or cross-resistance in populations of harmful organisms to the active substance(s), or to related active substances, should be provided.

Where there is evidence or information to suggest that, in commercial use, the development of resistance is likely, evidence should be generated and submitted as to the sensitivity of the population of the harmful organism concerned to the plant protection product. In such cases a management strategy designed to minimise the likelihood of resistance or cross-resistance developing in target species is required.

2.2.6. Quality and transformation processes

Sufficient information should be provided to permit an evaluation of the possible occurrence of taint or odour or other quality aspects of plants or plant products after treatment with the plant protection product.

Testing should be conducted initially on the main crops on which the plant protection product is to be used, using, where relevant, the main methods of processing. Where effects are observed tests should be conducted at the normal rate of application.

When the treated plants or plant products are intended for use in transformation process such as wine making, brewing or bread-making and significant residues are




present at harvest, the possibility of adverse effects should be investigated if there are indications that the product could have an effect on the processes involved.

2.2.7. Following crops

Where there is evidence that significant biologically active residues of the active substance, its metabolites or degradation products, which may have an effect on succeeding crops, remain in soil or in plant materials up to sowing or planting time of possible succeeding crops, observations should be submitted on effects on likely succeeding crops. In addition, under EU Guidance Document on relevance of metabolites in groundwater (Ref. Sanco/221/2000-rev10, dated 25 Feb 2003), there is a requirement to assess the relevance of any groundwater metabolites. This must include the biological activity of any metabolites and the potential risk to crops e.g. from use of irrigation water.

2.2.8. Adjacent crops

Observations should be submitted on adverse effects on other plants, including the normal range of adjacent crops, when there are indications that the product could affect these plants via vapour drift. Consideration should also be given to the effects of spray drift and the effectiveness of tank cleaning.

2.2.9. Plant parts for propagation

The safety of products to propagating material must be addressed, except where the proposed uses preclude application to crops intended for production of seeds, cuttings, runners or tubers for planting, as appropriate. Where there is sufficient interval between application and harvest and no residues or metabolites are found in the relevant plant parts it may be possible to address this issue by a case making reference to residues and metabolism studies. Further advice on when data are required is given in Efficacy guideline 306.

2.2.10. Observations on non-target organisms

Any effects, positive or negative, on the incidence of other harmful organisms, observed in tests, should be reported. Any observed environmental effects should also be reported, especially effects on wildlife and/or beneficial organisms.

2.2.11. Use in mixtures

Where there is a recommendation to use a product in mixture information should be provided on the effectiveness and safety of such use. This includes both positive recommendations for the use of mixtures to improve control and convenience mixtures.

2.2.12. Use of products containing more than one active substance

Where an active substance is co-formulated in a product with one or more other active substances all the above areas must be addressed. Particular attention must be paid to justification for the inclusion of each active substance in the product, as

http://www.pesticides.gov.uk/Migrated-Resources/Documents/R/RelevantMetabolites.pdf

http://www.pesticides.gov.uk/Migrated-Resources/Documents/G/gde306.pdf




well as a justification of the product dose and any resistance implications and management strategy arising from such a co-formulation. The amount of data generated using the co-formulated product to address these points will depend on the data already available for any single active products, and whether there are significant changes in use pattern. Additional guidance on the justification of mixtures, particularly for insecticides, is available in Efficacy guideline 607.

The simplest case would be where two actives with different target ranges are co-formulated and apply the same equivalent dose as the individual products. Provided dose justification has been addressed for the actives applied alone then no further data are required, although a case should be provided to confirm that the doses are equivalent to those applied by each single active product. A limited number of trials should be conducted to confirm the effectiveness and crop safety of the formulation, and demonstrate that there are no adverse (antagonistic) effects.

If the co-formulated product contains active substances with overlapping activity on particular targets, then evidence to support dose justification will be required. Because of the potential effects of the combined activity, this is considered relevant regardless of the relative doses applied in the co-formulated product compared with the single active products. These data can be generated as part of the trials programme to again demonstrate effectiveness and crop safety as discussed above. For these co-formulated products, where it may be the case that significantly different doses are applied, it is possible that a greater number of trials will be required particularly if there are multiple targets.

Further information concerning formulation changes, and in particular changes to active substance content are discussed in section 4.3.

2.3. Differences in areas addressed under COPR

Under COPR less emphasis is placed on the following areas.

● Preliminary tests

● Trials guidelines

● Resistance management

● Quality and transformation processes

● Adjacent crops

● Plant parts for propagation

In addition there is no requirement for doses other than those recommended on the label to be tested (dose justification) or for the effect of treatments on beneficial organisms to be tested.





3. Meeting Efficacy Requirements

3.1. Introduction

This section provides guidance on the general principles of meeting CRD's efficacy requirements. Guidance on specific situations is provided in Section 4, Situation-Specific Guidance on Meeting Efficacy Requirements or as separate guidelines as listed in Section 5.

Relevant information should be provided to support all direct and implicit claims relating to plant protection that appear on a label. The information should cover the range of circumstances likely to be encountered in practical use, including a representative range of climatic, crop and agronomic conditions. The data can come from a range of sources including:

● Extrapolation of data supplied to support existing approvals - see section 3.5 (Extrapolation) and 4.3 (Comparability of pesticide formulations).

● Public domain information such as published papers - see section 3.6.

● Confidential information owned by others, provided you have been given a legal right to access it - see Confidential information owned by others, provided you have been given a legal right to access it - see The Applicant Guide guidance document on the protection of data.

● Experimental trials - see section 3.8.

For major crop/pest uses, information is likely to come primarily from field trials either directly using the products, crops and target organisms of interest or by extrapolation from appropriate trials. Other sources of information are likely only to be of use in supplementing results from these sources. For qualified recommendations (see section 3.9.4, Limited efficacy data for minor uses: Qualified recommendations) and minor uses, good results from other data sources(s) could largely replace the need for replicated trials.

Information from different sources should not be treated in isolation, but should be drawn together to form an overall picture of how the proposed label recommendations are supported by the evidence. For example, an extrapolation to a related pest could be supported by evidence from results of user trials, or data from trials carried out overseas might be supported by UK public domain evidence. Applicants should note that well-researched and argued cases increase the chance of an application being successful.

3.1.1. Biological control agents (including pheromones)

Biological control agents (BCAs) are micro-organisms used as pesticides and must be registered in the same way as chemical pesticides. Pheromones and other semiochemicals are substances that cause behavioural responses in insects and may be used for example to repel insects or disrupt mating, they must also be registered if used for pest control purposes. Because many of these agents occur naturally, and in some cases require extremely small quantities to be effective they

http://www.pesticides.gov.uk/guidance/industries/pesticides/topics/pesticide-approvals/pesticides-registration/applicant-guide/the-applicant-guide-the-protection-of-data




may have a reduced toxicological and environmental effects compared to chemical pesticides. However, although in some cases they can be highly effective, BCAs often have a lower level of effectiveness than chemical pesticides. Despite this they have a role to play in pest control and can be important components of integrated pest management systems. Although the efficacy data requirements for these agents are broadly the same as for chemical pesticides, specific allowances are made for their particular characteristics. Further information is given in sections 3.3 and 4.2.

3.2. Presentation of efficacy information

The preparation of a case to explain how the supporting evidence supports the recommended uses of the product is a requirement for all applications. This provides an opportunity to explain and justify the proposed label and improves the efficiency of the evaluation greatly reducing the queries that may arise.

Efficacy data submitted for evaluation under PPPR should be in the form of a Biological Assessment Dossier (BAD). Efficacy data submitted for evaluation under COPR, may be submitted in the format of either a BAD or an efficacy overview. Separate guidelines for the preparation of Biological Assessment Dossiers and Efficacy Overviews are available from CRD, see section 5, Efficacy Guidelines.

Guidance developed within the Standing Committee on Plant Health (SANCO/3989/2001) identifies that as from 31 December 2004 all dossiers should be submitted in OECD format on the basis of the OECD dossier guidance. CRD is aware that there are differences with the OECD format compared to that of the Biological Assessment Dossier, both in terms of covering all relevant data requirements and also in the presentation format. CRD is therefore still prepared to accept dossiers to the ‘old’ BAD format.

Where dossiers are submitted to the OECD format it is imperative that applicants address all the requirements as detailed in EC Council Directive 91/414/EEC, and in subsequent directives such as 93/71. In particular, areas such as impact on the quality of plants and plant products, effects on the processing procedure, and effects on the yield of treated plants must be addressed. In addition in the presentation of efficacy studies, dose rates lower than recommended must be included and an assessment of whether the dose is the minimum necessary for approval to be recommended must be made. Applicants should also consider carefully the format of the summary tables to ensure that all relevant information is presented, and are advised to cross-reference with the examples of summary tables provided in Efficacy guideline 101 (Preparation of a Biological Assessment Dossier) to ensure that the relevant headings and information are included. For example, the OECD summary table example does not include information on weed numbers in the plots, something that is essential in determining the validity of the trial.

The OECD guidance is available at http://www.oecd.org/dataoecd/1/19/1944026.pdf.





http://www.oecd.org/dataoecd/1/19/1944026.pdf




3.3. Levels of control expected to be demonstrated

The aim of the evaluation of the submitted efficacy information is to ensure the label claims are supported and reflect the actual performance of the product. The performance provided should typically be in line with a commercially acceptable standard treatment unless the product has particular benefits such as specific activity against a target, compatibility with biological control or use in anti-resistance strategies when a lower level of effectiveness may be acceptable. Further information is available in EPPO guideline PP 1/214, Principles of Acceptable Efficacy. The following guidance broadly reflects the currently applied performance requirements for label claims. This is not a rigid framework for label claims and, if other claims are considered to be more fitting to the situation and product performance, these should be requested. This may be particularly relevant to biological control agents where levels of control may be variable or sensitive to environmental changes.

3.3.1. Pests

In considering data submitted towards justification of claims of effectiveness against pests, a number of factors will need to be taken into account when considering and interpreting the level of control demonstrated. These include the time of assessment in relation to application, the duration of effectiveness and the potential for re-invasion, and any recommendations for repeat applications.

Table 8.2; Levels of pest control expected for effectiveness claims

Level of effectiveness Label claim appropriate

Consistent control commonly above 80%

Control

Control, between 60 and 80% Useful level of control (moderate control may also be used)

Lower levels of control e.g. 40-60%; lower in exceptional cases.

Some control/reduction (in numbers or damage)

For a claim for effectiveness below 80% to be recommended for approval, the level of control demonstrated for that pest must be considered worthwhile for protection of the crop. Further justification will be required for such claims to be approved for significant target pests where a high level of control would typically be expected, for example where incidental control of a target is given when the application is directed at a different target pest, or they may be related to a reduction in damage caused by the target pest (e.g. slugs). For some pests particularly those affecting the quality of the crop, higher levels of consistent control (i.e. above 85%) would need to be demonstrated. Examples of pests falling into this category are pea moth and codling moth.




3.3.2. Diseases

Disease may be assessed as either severity or incidence. Measurement of disease incidence is particularly useful when low levels of disease are present but may be of little value when infection is more widespread, when severity is more likely to give a useful measurement of disease control. There is normally no benefit in reporting both. Table 8.3 indicates the levels of control expected to be demonstrated to support label claims for diseases and should be used where either severity or incidence are recorded as a percentage or other linear scale.

Table 8.3; Levels of disease control expected for effectiveness claims


80% and above Control

60-80% Partial/moderate/useful level of control

40-60% Reduction/some control

These criteria are not appropriate in cases where disease control is assessed as a score on a non-linear scale. These scales are often relatively coarse with as few as four divisions. With such scales meaningful levels of control can be difficult to determine unless disease pressure is relatively high. Table 8.4 indicates the levels of control expected to be demonstrated to support label claims for diseases where measurements are made on a non-linear scale. In addition, statistical analysis of assessments on a non linear scale is generally not appropriate. Even the calculation of means should be avoided. When recording and assessing such results it may be better to assign letters rather than numbers to the steps on the scale to avoid the temptation to analyse them numerically.

Table 8.4; Levels of disease control expected for effectiveness claims when using a non-linear scale


Consistently reduces disease to below 20-25%, normally the lowest class.

Control

Reduces disease to<20-25% in the majority of cases

Partial/moderate/useful level of control

Clear reduction in disease Reduction/some control

For some diseases, particularly those affecting the quality of the crop, higher levels of consistent control will need to be demonstrated. For a claim of control of seed borne pathogens (e.g. bunt, loose smut, leaf stripe), a product needs to be 98% effective or better. For leaf stripe and loose smut, control in the region of 85-95% would allow the claim for moderate control with the condition that seed cannot be used for multiplication purposes.

In some cases an argument may also be made for higher claims than are justified by disease control alone. For stem base diseases of cereals, for example, a claim of control may be appropriate even when disease control is not consistently above 80%, if it can be shown that the treatment significantly reduces lodging and/or disease levels are kept to a level where they have no significant effect on yield.




3.3.3. Weeds

In arable and horticultural field crops, the label claim supported by a certain level of weed control is as follows:

Table 8.5; Levels of weed control expected for effectiveness claims

Label claim appropriate Level of effectiveness

Susceptible Consistent control of 85% and above (see below †)

Moderately susceptible More variable control, mean 75-85%, but with results often above 85%

Moderately resistant Variable control, Mean 60-75%, but some results above this level.

Resistant Poor control below the levels given above

† To ensure worthwhile levels of control of certain important weeds in field crops, all these categories are raised with the susceptible rating being as follows: pernicious grass weeds where seed return must be prevented, e.g. black-grass and wild-oats, 95% and above, cleavers 90% and above.

For perennial weeds, assessments of control levels in the year following treatment will be important in determining the claim allowed.

3.3.4. Repeat applications

In many situations a repeat application will be required (e.g. regrowth, subsequent germination or reinvasion). The timing of assessments following treatment will be important in determining levels of control. Providing the label clearly explains the effectiveness of the product, the claims above are still appropriate.

3.4. Overseas evidence

Information from work carried out overseas may be acceptable to support an application. However the relevance of any overseas evidence should be carefully considered and a case made based on the parameters most relevant to the particular use under consideration. The level of supporting detail included for overseas data should be at least the same as that expected from UK trials. This includes the requirement that organisations conducting work in EU member states are officially recognised where a scheme exists at the time (See section 3.8.1, Official recognition and Efficacy guideline 110)

The relevance of the conditions under which the trials were conducted to the proposed conditions for use should be demonstrated. This would usually be done by comparison to the general conditions that the crop or situation would experience in the UK. The major issues are detailed below. The list is not exhaustive, and applicants may be aware of other factors that might influence relevance in specific cases. Applicants are therefore encouraged to consider the areas that are relevant to the use in question, rather than submitting all information, some of which may be irrelevant (e.g. soil type for foliar acting pesticides). Applicants may wish to construct a general case for use of data from a particular area which could then be used as a basis for future applications involving trials in that area.





3.4.1. Climate

Typically, information such as mean maximum and minimum day and night temperatures and rainfall (note that as well as monthly means, intensity of rainfall may also be useful) could be required. Other factors such as humidity, wind speed and intensity of sunlight may also be useful depending on the activity of the pesticide. It is for the applicant to decide on the relevance of these individual aspects, but generally the closer the locality of the trials is to the UK the less extensive is the need for full climatic data. It may be useful to present a comparison of the relevant conditions in UK and overseas trials presented in the data package.

The Crop Protection Association (CPA) produced a climate justification paper which was agreed with PSD. This defined an area of Northern Europe within which climate may be considered comparable. Subsequent to this, EPPO produced the guideline ‘Guidance on comparable climates’ (PP 1/241(1). This divides Europe into four regions, within which climate is considered comparable. The UK is within a defined region very similar to that drawn up in the original UK CPA paper. This guidance is considered to supersede that of the original CPA paper and should be used instead.

It is also important to remember that climate is only one part of the case for justification of non-UK data, and the other relevant factors discussed in this section will still need to be addressed.

3.4.2. Edaphic conditions

For soil-applied products it is important to record soil types (converted where possible to the Soil Survey of England and Wales soil texture system1), organic matter content and pH. In addition it may also be important to record soil moisture content/deficit over the duration of the trial.

3.4.3. Agronomic conditions

Cultural conditions and agronomy, (e.g. cultivations used, application methods, cultivars, fertiliser regime, relative times of planting and harvest) may need to be considered if it is thought that these differ from UK conditions.

3.4.4. Differences in target pest pressures

Specific details on the target pest, and whether the conditions encountered in the overseas trials are likely to represent a harsher or less harsh test of the product (for both effectiveness and crop safety), will sometimes be necessary. Such detail would include differences in the epidemiology of diseases, population dynamics of insects and other pests and differences in races of organism to be controlled. For example damson-hop aphid has a longer period of immigration to hops and invasions are more severe than on the Continent. Overseas data are therefore unlikely to be relevant to the UK situation.

1 Rural Development Service Technical Advice Note 52; Soil Texture. http://naturalengland.etraderstores.com/NaturalEnglandShop/UserFiles/Files/tan_52.pdf

http://naturalengland.etraderstores.com/NaturalEnglandShop/UserFiles/Files/tan_52.pdf




3.5. Extrapolation

Provided a sound database is available it may be possible to extrapolate information from one target or crop to another closely related one, between different cropping situations or between closely related formulations. Extrapolation may be possible for control of the same target on other crops, for control of related targets on the same/other crops, or between crops for crop safety. It may also be possible to extrapolate from all uses of a product of a similar formulation containing the same active substance(s), e.g. from professional to home garden use of a product. Extrapolation may be used to form either all or part of the supporting case for approval.

3.5.1. Availability of a sound database

An important factor when considering extrapolation is that the efficacy data used as the basis of the extrapolation must be adequate in quality and quantity, i.e. extrapolation must be from a sound database.

If conditions have been such as to test the product severely, and it has still performed consistently well, relatively few results will be sufficient to support the extrapolation. However, there will be times when the very nature of the situation gives rise to high variability and more trials will then be necessary. If extrapolation is supported by an efficacy database for more than one use (e.g. where the pest is controlled on two or more different crops, or where crop safety has been demonstrated on a range of crops) then extrapolation is more likely to be acceptable.

3.5.2. Biological basis for extrapolation

A sound biological basis for extrapolation is essential. A close taxonomic relationship cannot always be assumed to be well correlated with overall biology and behaviour of the target organism(s). For example, the summer fruit tortrix moth is not controlled by many insecticides that are effective against fruit tree tortrix moths. In addition, the same organism may not behave in the same way for different crops/situations. Equally, crops that are taxonomically related may be quite different, for example in their growth habit, leaf surface or in terms of the parts of the plant that are harvested. All aspects of the pest biology and behaviour, and the crop biology and uses should be carefully considered in making a case for extrapolation.

3.5.3. Choice of use from which to extrapolate

If a trials programme is being designed to support an extrapolation, it is advisable to consider which crop/pest combinations are likely to be most suitable for this purpose. It should not be assumed that the crop with the largest area in the UK should automatically be the subject of the greatest number of trials. It may be better to put more emphasis on a less widely encountered crop. For example in the case of herbicides, if the crop is less competitive with the weeds, or in the case of insecticides/fungicides if the organism to be controlled is usually more difficult to control on the less widely grown crop. This is because the case for extrapolation to less susceptible/more competitive crops is likely to be more convincing. The same is true for considerations of crop safety. If data are provided from a crop that is




considered to be more susceptible to damage by pesticide treatments then an extrapolation will be easier to justify.

It should also be borne in mind that the pest problems for any one crop may be more diverse and more common than for another, so that the probability of obtaining data useful for extrapolation to other crops may be correspondingly higher.

3.5.4. Further guidance on extrapolation

Further guidance on extrapolation in specific situations is contained in section 4.4 below.

In addition, a guidance document titled ‘Proposal for extending and harmonizing efficacy and crop safety extrapolations to reduce the need for efficacy trials on minor crops’ is available. This document was produced by PSD under a Commission contract. It makes proposals for efficacy extrapolations to facilitate the approval of extensions of use onto minor crops and against minor targets. This guidance has now formed the basis of EPPO guideline PP 1/257(1) ‘Efficacy and crop safety extrapolations for minor uses’ which lays out the general principles for extrapolation, and includes as an appendix various specific examples. It should be noted that further work is underway to produce specific EPPO guidelines for specific target/crop situations. Applicants should refer to this general guidance as well as any future guidelines.

3.6. Public domain evidence

The use of public domain evidence, such as papers published in scientific journals, conference proceedings etc, is an acceptable way of supporting label claims. It is important for the applicant to explain how any information directly supports the claims made. In addition, if the evidence cited is from field or glasshouse trials conducted outside the UK, then a case arguing the relevance of the conditions to the UK will be required. The following factors should be considered when using such information.

3.6.1. Formulations

The efficacy of many active substances is affected by formulation and therefore, applicants should give due consideration to whether the formulation(s) in the public domain data directly support the product under consideration for approval. For guidance on this aspect, please see section 4.3, Comparability of pesticide formulations.

3.6.2. Data protection

When considering the use of public domain data, applicants should be aware that CRD consider labels of other similar products (containing the same active substance) to be supported by data which are not in the public domain. An application that makes identical or very similar claims to other products will not, therefore, be considered acceptable unless directly supported by adequate data. You should consult The Applicant Guide guidance document on the protection of data for guidance on CRD's data protection policy.

http://www.pesticides.gov.uk/Migrated-Resources/Documents/S/SANCO_D3_S12-395857.pdf



http://archives.eppo.org/EPPOStandards/efficacy.htm

http://archives.eppo.org/EPPOStandards/efficacy.htm

http://www.pesticides.gov.uk/guidance/industries/pesticides/topics/pesticide-approvals/pesticides-registration/applicant-guide/the-applicant-guide-the-protection-of-data




3.6.3. Weed Control and Pest and Disease Control Handbooks

CRD have always accepted recommendations given in the 'Weed Control Handbook2' with no further data required, as long as the proposed label uses are within the range given in the Handbook and the formulations are comparable. However the 'Pest and Disease Control Handbook3' is based on product labels and not peer reviewed public domain data, and therefore cannot be used to support applications.

3.6.4. Presentation of public domain data

When making use of public domain evidence, it is not sufficient to simply provide a copy of the original papers. The relevant methodologies and results should be properly summarised in the submission and discussed in sufficient detail to demonstrate their relevance to the proposed label use. It may be helpful to submit a copy of the references used, especially of the more relevant ones. Applicants should be prepared to supply a copy of any references not included in the submission, if necessary with an English translation, on request. Failure to do so may result in a lower level of approval than that requested or the affected uses being omitted from the recommendation for approval. Information on the use of efficacy data in the public domain was issued in the Pesticides Register, Issue 5, May 1995 (available from HMSO, ISSN 0955-7458).

3.7. Data owned by others

Where an application relies on confidential data owned by a third party, for example data used to support a previous application from another company that is still under data protection, a valid letter of access must be submitted. These must be either original signed copies or copies of letters previously submitted to CRD. Full guidance on letters of access, including a suggested proforma, are available in The Applicant Guide guidance document on letters of access.

3.8. Experimental Data

3.8.1. Official recognition

With minor exceptions all efficacy data generated since 1st Jan 1998 must have been generated by an Officially Recognised Organisation.

The UK scheme for ‘Official Recognition of Efficacy Testing Organisations’ (’Official Recognition’) was designed in response to Community Directive 91/414/EEC (as amended by Commission Directive 93/71/EEC), which states that all efficacy testing for registration purposes must be carried out by ‘Official’ or ‘Officially Recognised’ efficacy testing organisations. In other Member States ‘Official Recognition’ is commonly referred to as ‘Good Experimental Practice’ (GEP).

2 Fryer, JD and Makepeace, RJ (Eds)(1978) Weed Control Handbook Volume II / Recommendations. Blackwell scientific publications, Oxford.

3 Scopes, N and Stables, L (Eds)(1989) Pest and Disease Control Handbook. British Crop Protection Council, Bracknell.

http://www.pesticides.gov.uk/guidance/industries/pesticides/topics/pesticide-approvals/pesticides-registration/applicant-guide/the-applicant-guide-letters-of-access

http://ec.europa.eu/food/plant/protection/evaluation/legal_en.htm




The UK ‘Official Recognition' scheme came into force on 1st January 1998. Efficacy data generated in the UK after this date must be carried out by ‘Officially Recognised’ efficacy testing organisations.

For full details of the data that falls under the requirements of Official Recognition see Efficacy guideline 110.

Data produced in the UK

All applications for products approvals (i.e. new substances, committee stream, normal stream etc.) which contain efficacy data generated from trials carried out in the UK after 1st January 1998 must be supported by ‘Official Recognition’ certificate numbers (e.g. ORETO 001) for all of the organisations concerned. The ‘Official Recognition’ categories stated on the certificate must be relevant to the type of data submitted (e.g. Stored Crops), and it must be valid for the period during which the data were produced. This also means that, within the Biological Assessment Dossier, applicants must clearly identify which organisations undertook the work.

Data produced elsewhere in the European Union

When an application for product approval contains efficacy data produced elsewhere in the European Union, CRD require evidence of whatever constitutes ‘Official Recognition’/‘GEP’ in that Member State (e.g. copies of relevant and valid certificates). This evidence should demonstrate that the organisation carrying out the work was ‘Officially Recognised’ at the time. The exceptions to this are where the data were produced before an ‘Official Recognition’ scheme was established in that Member State or where the data were generated by ‘Official’ testing stations. However, in some Member States ‘Official’ testing stations are also certificated.

‘Official Recognition’/‘GEP’ schemes vary slightly between different Member States, in terms of their start dates, scope and the evidence required to achieve certification. This is because Member States were individually responsible for implementing the requirements of Directive 91/414/EEC.

3.8.2. Designing a trials programme

The trials programme should be designed to cover each distinct region of the country within which the conditions and practices are broadly similar, and where it is intended to use the product. Within each region trial sites should be distributed across the main relevant growing areas and should include the main relevant plant cultivars occurring in each region.

The programme should be designed to assess the performance of the product in each region under the conditions likely to occur there during the relevant period(s) of the year. Such studies should produce adequate data to permit conclusions to be drawn concerning the product's performance in respect of climate, soil type, plant cultivar, pest, pathogen or weed species as appropriate under relevant conditions of use.

The programme should normally extend over a period of at least two years in order to assess the effect of under seasonal differences. In some situations results obtained from a lesser period may be acceptable, for example when considering closely





similar products, a change in formulation or method of application, certain protected crops, minor uses, certain home garden products etc.

3.9. Conducting field trials

The sections below cover only basic principles. Further guidance and advice on meeting data requirements in specific situations is given in Section 4 and in separate guidelines listed in Section 5. Detailed specific advice on conducting trials is given in the guidelines for the evaluation of plant protection products issued by the European and Mediterranean Plant Protection Organisation (EPPO). EPPO guidelines are recognised by CRD, and in the European Directives associated with the registration of plant protection products, as the standard reference for trials methodology. As such they should be followed unless a sound justification can be given for not doing so. EPPO guidelines are obtainable from:

EPPO, 1 rue Le Notre, 75016 PARIS, FRANCE.

3.9.1. Number of trials

The applicant should aim to provide data to support the claims made on the product label and to provide evidence of the suitability and crop safety of the product for the use envisaged. The number of trials required to achieve this depends on many factors such as:

● The extent of the knowledge already gained on the active substance or product

● The importance of the crop/animal/produce and the significance of the harmful organism

● Availability of testing possibilities e.g. rare occurrence of the harmful organism

As a general rule, a total of ten trials results demonstrating efficacy and ten demonstrating crop safety are required for approval. For insecticides and fungicides some, or possibly all, data on crop safety may be obtained by appropriate assessment of effectiveness trials. A case may be made for fewer trials to be accepted, for example where there is a large amount of supporting evidence or when there is a very high level of consistency in different trials. In all cases the trials programme should be carried out over at least 2 years.

Additional claims will also require ten trials, for both effectiveness and crop safety. Again a case may be made to reduce the number of trials in certain circumstances. For example CRD only normally require three consistent trials for minor crops or targets, provided data on a relevant major target have already been considered, and a level of extrapolation may be permitted between different crops for a single target organism that affects more than one crop.

3.9.2. Location of field trial sites

The crops chosen for experiments may be specifically grown for experimental use or be part of crops grown for commercial purposes, but in all cases should be grown

http://www.eppo.org/




according to normal commercial practice. They should be located in areas representative of those in which the crop and harmful organism normally occur.

If there is a possibility that soil types may affect the action of a product, sites should be chosen which are representative of the range of soil types typically encountered. The experimental site should be uniform and crops should preferably not be under any stress other than that attributable to the problem to be treated (except where the effects of stress are being investigated). All other cultural operations apart from that being tested, should be according to normal practice and should be recorded.

3.9.3. Trial design

The design, analysis and reporting of trials should be in accordance with EPPO guidelines 152 and 181 and where available more specific the EPPO guidelines applicable to the situation.

The design of the trial should, where relevant, permit a statistical evaluation. Usually a randomised block design is adequate. Each block should generally contain one plot treated with the pesticide to be evaluated, one treated with a suitable reference product (positive control) and an untreated control. The plots should be randomly distributed within the block. Consideration should be given as to whether it is likely that design and analysis as a trial series is appropriate rather than, or as well as, analysis of results from the individual trials conducted. This may affect trial design as a more statistically powerful test is achieved through the use of larger numbers of trials than through greater numbers of replicates in each trial. See EPPO guideline 152 and Efficacy guideline 111 for further information on the statistical analysis of efficacy data.

The design of the trials should not be made any more complicated than is required by the objectives of the test. Where it is necessary to introduce into the experiment factors, in addition to the treatments of the pesticide under study at the recommended dose, such as various times of application or other doses, this can be accomplished by splitting the main plots into sub-plots, provided that the size of the sub-plots are still sufficient to allow a reliable evaluation.

Plot size

The most suitable plot size depends upon many factors, including the particular crop, pest, disease or weed situation, the mobility of the target organism, the available equipment for application of the treatment and harvesting of the crop. Since guard rows/areas often have to be included, the overall plot size should be sufficiently large to allow the net plots on which periodic sampling and evaluation of the crop yield or harvest are carried out to be of adequate size. Guidance on the minimum net plot size is usually indicated in individual EPPO guidelines.

The number of replications required depends on plot size, number of treatments and uniformity of distribution of the target organism. The number of replications required is also related to the particular techniques employed. Further specific guidance is given in EPPO guidelines, but four replicates is normally considered to be the minimum number for field experiments. Three replicates are usually acceptable for





the evaluation of post-emergence weed control by herbicides, provided the yields are not intended to be measured.

Control and untreated areas

Untreated areas are normally an integral part of a trial. There should be at least one per replicate. If there are ten or more experimental treatments there should be at least two untreated plots in each replicate, provided there are at least four replicates. Where there are only three replicates then eight or more treatments would require at least two untreated plots. If maintaining the untreated plots at the same area as treated plots represents an unacceptable economic loss their size may be reduced, but not the number of untreated plots. Except in trials designed to test safety to the crop, these plots may be treated after they have been evaluated. Exceptionally (e.g. aphids in commercial hops) the requirement for untreated control plots may be waived. Positive controls should be suitable approved products, but in appropriate cases there may need to be (in addition or instead) a control not exposed to the harmful organism.

Target organism

As far as possible the target organism should be present, or be expected to occur evenly distributed and at a level of agronomic importance. The organism must be identified and described by its full scientific name. Where relevant, subspecies, variety and pathotype, etc. should be stated. Stage of growth, density, frequency or level of infestation/infection and other factors having a bearing on the situation should be noted and, if necessary, be quantified before treatment.

A naturally occurring infestation/infection is preferred. If artificial inoculation of a pathogen or introduction of a pest or weed is necessary, this should be recorded and the procedure described. Untreated and standard treated plots should be infested, inoculated or populated in the same manner as plots to be treated with the product under test. Consideration should be given to allowing a suitable period of time following inoculation for the infection or pest to become established before treatment. Additional useful information (especially on crop safety) may be obtained in appropriate cases from the inclusion of treated but uninoculated/uninfested/unpopulated plots.

Trials should include different stages of growth of the harmful species where relevant. Trials should also include different strains or races where these are likely to show different degrees of susceptibility. Evidence of effect in appropriate representative species, cultivars or breeds having resistance to the harmful organisms in question should be provided where such resistance is known or suspected.

Dose

The dose at which the product is likely to be recommended should be included in trials. In trials to test efficacy, doses above and below the recommended dose should, where appropriate, also be included. In trials to determine safety to crops, the recommended dose, and for herbicides at least double the recommended dose, should be tested. For insecticides and fungicides inclusion of a higher than recommended dose is not a requirement for crop safety unless effects are seen at




the recommended dose. Nevertheless inclusion of a greater than recommended dose for such products may help to give greater confidence in the results obtained and should therefore be given due consideration. Any adjuvants, e.g. spreaders or anti-foaming agents which it is intended to recommend should be mixed with the product should be applied with it in the trials. It may be advisable to test the product and the adjuvants separately to detect a phytotoxic effect.

The test material should not be applied in mixture with other products, fertilisers, or other substances (other than adjuvants and diluents) except where the purpose is to obtain information on the performance of such mixtures, or where the inclusion of such products or substances would normally be considered as good agricultural practice. Where two or more products in tank mixture are being tested, the individual products should be tested in the same trial.

Application method and water volume

The method and conditions of application should be the same, or as like as possible to that to be recommended for the product. The application pattern used in trials should be similar to that used in commercial practice, both in particle size and distribution and in deposition on the treated surfaces. For sprays the volume and diluent should be as recommended for commercial use except where these factors are being evaluated.

The water volumes that are to be recommended on the product label should be considered to be a pre-requisite for the protocols of trials to demonstrate the effectiveness and crop safety of a product. For situations where a dilution rather than a specific volume of water per hectare is to be recommended trials should reflect the recommendation. Where appropriate information on crop or canopy size should be provided. For proposed uses on apple, applicants should refer to the UK developed dose adjustment scheme (‘PACE’), which is based on a ‘crop adjustment factor (CAF)’. CAF values should be recorded in any apple trials. Further details are available from Efficacy guideline 403 ‘Provision of information on tree canopy size in efficacy and residue trials in apple orchards’. It is accepted for most arable and horticultural crops that the range of water volumes, using standard hydraulic nozzles, is 200 - 400 litres/ha. Trials data using any water volume within this range are acceptable for such label recommendations. For all other label recommendations there is a need for trials data using the recommended water volumes or a reasoned case as to why trials data using a different volume are applicable.

Timing and treatments

The timing to be recommended in practice should be tested. Inclusion of earlier and later timings, where appropriate, may provide additional useful information. Where repeated application is the norm the timing of the first application should be that expected to be recommended for the product being tested. Different frequencies of application may be compared. The optimum interval between applications may have to be established by experimentation.





Recording and assessment

Records of the weather before, at and after treatments should be kept and relevant data included in the reports of experiments. Rainfall, frost, air and soil temperatures, and air humidity are usually the most important factors influencing results. Other measurements e.g. wind speed and direction may be required in some circumstances. If experimental crops are not grown in their usual environment this should be stated (e.g. field crops in pots or under temporary or permanent shelter from the weather).

Variety of crop, stage and vigour of growth and all other relevant information should be recorded on the date of treatment. Crop growth stage should be defined either by using an accepted code (e.g. growth stage keys published by EPPO), or by a detailed description. A pre-treatment assessment is often also essential to determine the level of infestation/infection and stage of development of the harmful organism and/or stage of growth and condition of the crop.

One or more post-treatment assessments should be made and these should be timed so as to elucidate the maximum of information on the behaviour of the product and its duration of effect, whilst also avoiding undue damage to the experimental area and needless expenditure (frequent inspection may be necessary to minimise the number of assessments). Assessment at different stages of growth of the target organism and/or of the crop may be required. Further specific guidance on assessment methodology is given in EPPO guidelines.

Results should be assessed by counts or measurements wherever possible. Only when the use of such assessment methods is inappropriate should any other methods, such as scoring or grading be used. Any such method should be related to an absolute count or other measurement on the untreated or the standard treatment (or both). When scoring schemes are to be used, widely accepted scoring systems such as those in EPPO guidelines should be used in preference to others.

Where appropriate data should be statistically analysed, and methods fully described. Raw data need not be submitted but should be held by the applicant for reference in case of a need for clarification. See EPPO guideline 152 and Efficacy guideline 111 for further information.

3.9.4. Limited efficacy data for minor uses: Qualified recommendations

An application for pesticide approval is expected to include evidence to support the claims made about the efficacy of a product. However, this evidence may be difficult or uneconomic to obtain where sporadic pests or other problems are concerned or where small scale crops are involved. As a result, it has been agreed that in certain circumstances approval may be given on the basis of limited evidence of effectiveness and/or crop safety. However, all such applications must still meet the full requirements with regard to safety to the health of humans, animals, non-target plants and the environment, before any approval can be given.





Qualified recommendations for minor uses

Qualified recommendations on the basis of limited efficacy data may be considered for:

● Use on a minor crop/situation.

● Infrequent treatment of a major crop/situation.

● Use to control a sporadic pest/disease/weed/other problem.

The decision on what constitutes a ‘minor use’ rests with the Registration Authority. Potential applicants are advised to contact CRD’s Environment Branch to discuss whether or not the proposed use qualifies as ‘minor’ prior to making an application.

Evidence of efficacy

To support an application for approval under these arrangements the evidence submitted must satisfy CRD that there is a reasonably high probability that the claims of the products effectiveness and crop safety (where applicable) are justified.

Evidence to support a qualified efficacy recommendation will usually take the form of a justified extrapolation from data on the pest on other crops or from data on related pests. Where relevant, foreign data may be submitted. Recorded field observations may also provide useful evidence, particularly on crop safety.

Uses given approval on the basis of limited efficacy data must be clearly identified as "Qualified Minor Use Recommendation[s]" on the label under 'recommendations for use'.

3.9.5. User derived evidence

In some situations efficacy data to support an application for approval can be generated from trials conducted by a commercial user. In some cases large scale user trials may be more appropriate than replicated small plot field trials. For example, for crop safety in top fruit the variability from tree to tree can be very high, so assessments from small plot trials may detect only gross effects.

When carrying out user-trials applicants should ensure pesticides are used within the conditions of approval, or that they are the subject of the relevant experimental permit (see The Applicant Guide guidance document on application streams).

The acceptability of user-derived evidence

Under Commission Directive 93/71/EEC, all efficacy data should be generated by ‘an official or officially recognised testing facility or organisation’. The UK ‘Official Recognition of Efficacy Testing Facilities’ (ORETO) scheme makes provision for user-derived evidence by allowing such work to be carried out by suitable qualified personnel under the direct supervision of an ‘Officially Recognised’ facility. The UK ORETO scheme came into force on 1st January 1998. The acceptability of user-derived evidence generated after this date is conditional upon the supervising organisation supplying a relevant and valid ‘Official Recognition’ certificate.

http://www.pesticides.gov.uk/guidance/industries/pesticides/topics/pesticide-approvals/pesticides-registration/applicant-guide/the-applicant-guide-application-streams-and-targets




Conducting user trials

The usefulness of results from user trials is largely dependent upon the appropriateness of the assessments, and the quality of the recording and reporting of the methods and results. The applicant should play an active role in supervising such trials, thereby ensuring that the maximum benefit is gained. Detailed guidelines on conducting user trials are available in Efficacy guideline 112.





4. Situation-Specific Guidance on Meeting Efficacy Requirements

This section gives specific guidance on the use of information to support applications and on generating information to support approvals in some of the most frequently encountered situations. Further guidance for other situations can be found in the efficacy guidelines a list of which is presented in section 5.

4.1. Extrapolation between glasshouse or growth room tests and outdoor use

The proceedings of the BCPC/SCI Conference "Comparing glasshouse and field pesticide performance II"4 report that glasshouse testing is not necessarily a good indicator of field performance. This means that for field-applied products, CRD judge that glasshouse-produced data are generally of limited value in establishing field performance. For products recommended for use under controlled conditions (e.g. glasshouse products, grain storage products, palatability testing of rodenticides), glasshouse/laboratory testing can be more relevant.

Applicants should make a clear case as to why an extrapolation from glasshouse to outdoor use is valid. Conditions in a glasshouse can affect the structure of plant surfaces, as well as pest biology, thereby changing the effectiveness and crop safety of a product. Particular caution is required in considering crop safety data obtained in protected conditions. In some cases the protected crops may be "softer" (perhaps because of a thinner layer of surface wax) and thus be more easily damaged. In other cases the damage on outdoor crops may be influenced by factors not found under protection (e.g. sudden temperature changes, frost, abrasion by soil particles, wind, drought, water-logging). It is suggested that applicants study the proceedings of the BCPC/SCI Conference "Comparing glasshouse and field pesticide performance II" before attempting to justify such extrapolations.

4.2. Biological Control Agents and pheromones

The extent of data required for BCAs and pheromones is generally the same as for other pesticides. However, consideration will be given to the nature of any particular agent. The following illustrate some of the issues that applicants should take into account when designing a trials programme.

● Use in protected environments: Many BCAs are only normally used in protected environments such as glasshouses. Because of the narrower range of environmental conditions typically encountered all pesticides for use in protected crops generally require fewer trials to demonstrate efficacy.

4 H G Hewitt, J Caseley, L G Copping, B T Grayson and D Tyson. (1994) Comparing Glasshouse and Field Pesticide Performance II. Proceedings of an international symposium held at the University of Canterbury 12-14 April 1994.




● Environmental conditions: Many biological control agents are sensitive to particular environmental conditions. Where BCAs are not used in protected environments the dossier must provide adequate evidence of the effect of environmental conditions on the products effectiveness in relation to the label recommendations. This can normally be achieved by conducting trials over two years.

● Crop safety: Agents that are not applied as broadcast sprays onto plants have reduced potential to cause phytotoxic effects. Although crop safety must always be considered a relatively simple case may often be sufficient.

● Pheromone trials: Because of the potential for pheromones and other semio-chemicals to disperse over a wide area it may not be always feasible to conduct trials with replicated or untreated control plots. Applicants are advised to talk to CRD before setting up trials programmes and, where relevant, refer to Efficacy Guideline 220 ‘Data requirements and trials design for mating disruption products’

4.3. Comparability of pesticide formulations

Formulation changes have the potential to influence the efficacy of a product as many co-formulants are added to a product to increase effectiveness against the target organism, directly or indirectly. This section is intended to give general guidance on the extent of efficacy testing required when, for the purposes of registration, a formulation is claimed to be comparable with another; and existing data on the ‘old’ formulation' are used to support approval of the ‘new’ formulation.

4.3.1. When is supporting data required?

Changes to surfactants, such as wetters or spreaders, including to the amount of surfactant, are normally regarded as changes that will require efficacy testing. It should be remembered that a change that improves effectiveness can have the opposite effect on crop safety and vice versa. Similarly changes in solvents or carriers can impact on performance and unless changes are considered minor (e.g. to a chemically very similar solvent) then efficacy testing is required. For granule carriers, the comments under ‘Herbicides used pre-emergence’ apply to other granule formulations e.g. insecticides and nematicides. Note that it is the applicants responsibility to justify the similarity of two formulations where they believe formulation differences are sufficiently similar that efficacy testing is not required. However there are some cases where supporting efficacy evidence is not required to show that the two products have comparable efficacy

Minor formulation changes.

The following changes to formulations are considered minor and do not usually require supporting efficacy evidence provided the change does not affect the amount of active substance or other co-formulants that are applied.

● Changes in the source of active substance.

http://www.pesticides.gov.uk/Migrated-Resources/Documents/E/Efficacy_Guideline_220.pdf




● Change in substances added to preserve the formulation in the container or to improve safety to non-targets, e.g. preservatives and anti-freeze - except for vertebrate control bait products.

● Changes in substances used to identify the formulation, e.g. dyes.

● Some changes to the fertiliser content of granular herbicide fertiliser based granules. The nature of the manufacturing process for granular herbicide fertiliser products means that often several different forms of nitrogen, phosphorus, potassium or other elements may be included. It is considered unlikely that variation in fertiliser base will affect the performance of the product. CRD will accept a range of formulation details for the fertiliser base component, for these products alone. Formulation details should include the expected concentration range of all the raw materials used in the production of the fertiliser base, and the minimum specification of the final formulated product. The latter must include the N:P:K ratio, active ingredient content, particle size, density and dust content. CRD must be notified of any additional materials used, and data or information must be provided showing that the change has no adverse effect on the product.)

● In general, changes of less than 10% in the amount of any formulation component applied, including the active substance, are considered to be minor and as such require no further data. With respect to efficacy, it is the amount of active substance and co-formulants applied to the target that is important, not the content in the formulation itself.

Attempting to significantly change a formulation, by making a series of minor changes in content (i.e. each within 10%) that would not in themselves require supporting data, is not acceptable. CRD will refer back to the original formulation for each change and where appropriate request supporting data.

Some products contain two or more co-formulants with the same function, e.g. wetters. Where this is the case, providing the co-formulants concerned are chemically similar, it may be acceptable to change the quantities of them by more than 10% providing the overall content of that group of co-formulants is not changed by more than 10%. A case to justify similarity of the co-formulants concerned should be provided.

Note of caution: Many applications for changes in formulation do not contain any information on the chemical nature of the co-formulants, nor any justification of the similarity between them. In the absence of any further information, CRD will generally err on the side of caution and refuse approval for the revised formulation.

Some products contain more than one active substance. Where changes are made to the ratios of the active substances within a product, even if these changes are less than 10% for each active substance, further efficacy consideration may be required, particularly in terms of effectiveness and dose justification. In particular it is not appropriate to make successive small changes to the active substance content which ultimately result in a significant difference in the ratio, unless there is




appropriate data to address the issues of efficacy, dose justification and crop safety, as relevant

Uses/types of products

For the following uses and types of product, although differences in formulation may exist, these are unlikely to affect efficacy and thus efficacy data are not required to show that the two formulations are comparable.

Simple salts in water Products that are simple salts in water are taken to be comparable to other products containing the same salt of an active substance Products containing different salts of the same active substance are taken to be comparable if both salts disassociate equally in water. Examples of active substances which can be formulated in this manner are, arylalkanoic acids (the 'hormone' herbicides), dicamba, and chlormequat

Herbicides used pre-emergence

It is generally accepted that once a formulation is present in soil then the co-formulants have no effect on performance. This means that for a product which is used before neither the crop or weeds have emerged, no efficacy data are required to establish comparability. If used pre-emergence of the crop on emerged weeds then only data on effectiveness are required. If used before weeds emerge on an emerged crop then only crop safety data are required. A case may be provided to reduce the data required where the herbicide is only active through the roots.

Exceptions to this are granular and capsule suspension formulations or slow release formulations, for which data may be required. For a change in size of granule or alteration of the material from which release occurs, data are required to show that efficacy is not affected. For the latter this may be based on physical property data, such as active substance release rate.

Other types of products used pre-emergence

For soil-applied/compost incorporated products other than herbicides, a case for a reduced comparability package may be considered, depending on the type of activity and the considerations of release rate and coverage given above for herbicides.

Seed treatments It may be possible to submit data showing that the loading of the active substance on treated seed is the same for both the old and new formulations rather than carry out field trials. Please consult CRD’s Environment Branch for further advice.




Fumigants Where the product is a fumigant then provided either; that gas is evolved from the formulations at a similar rate, or gas levels are maintained through monitoring and redosing, the formulation is unlikely to affect efficacy.

Groups of formulations

Companies may have access to existing data which demonstrate that a range of formulations of the same active substance are similarly effective and crop safe. Where this is so, a case may be accepted that it has already been demonstrated that formulations containing this active substance are broadly comparable. If only formulations of a similar type have been shown to have comparable efficacy then the case for comparability may be restricted to that formulation type, e.g. if three suspension concentrate (SC) formulations control a certain target then extrapolation to another SC might be possible but extrapolation to an emulsifiable concentrate might not.

In some cases, one formulation can be recommended at a lower dose of active substance than another formulation containing the same active substance. This could indicate that there is variation in the performance of different formulations containing that active substance, therefore broad comparability has not been established and efficacy comparability work will be required.

Knowledge of previous formulation changes with a particular active substance.

The intended change in formulation from the ‘old’ to the ‘new’ product may be similar to a change which has already taken place with that active substance or one with very similar properties. If the applicant has access to existing data which shows that this change in formulation did not affect efficacy, then comparability testing may not be required.

An applicant may have access to existing data that show that a number of formulation changes have taken place with an active substance and efficacy is always equivalent. In which case, it may be possible to make a case for a reduced level of comparability work when approval is sought for a further ‘new’ formulation.

Please Note: The examples given above are not exhaustive. If you are undertaking another change in formulation that you consider does not require efficacy testing, or where existing knowledge suggests a reduced package would be satisfactory or a case could be made, please consult CRD’s Environment Branch.




4.3.2. Extent of efficacy testing required to demonstrate comparability

A label will have been established for the approved product taking into account the acceptability of the levels of pest control achieved and whether any crop effects seen will affect yield. The tests described below are only relevant to establishing comparability of two formulations so that similar label claims can be made for the proposed product.

lxxiv) Generally, results from five appropriate trials are required. Both effectiveness and crop effects should be assessed in these trials on a selected range of target species and crops claimed on the label. Not all species and crops on the label need to be tested. If the label is very diverse in terms of the claims made then more trials are likely to be required, depending on the type of action of the product. On the other hand, where a particular target or crop can be identified as a good indicator of comparability, all trials may be carried out on this target/crop.

lxxv) Target organisms for examination in trials should be selected from the list of organisms claimed as controlled on the label. Those selected should include targets that are less well controlled by the product or are known to be more difficult to control with that type of product. Reduced doses can be included to provide a more severe test of comparability of effectiveness.

lxxvi) Crop safety should be examined on crops stated to be acceptable for treatment on the label. Crops selected should include any that are known to be more sensitive to the product and thus most likely to show damage to give the most testing examination of comparability.

lxxvii) Trials carried out in one growing season should be acceptable as long as they are carried out in different conditions and preferably in different situations, to reflect those possible from the label instructions. One seasons testing may also be sufficient where disease or pest challenge in that season has been adequate, or where the product is used under controlled conditions, e.g. glasshouse. Existing data on the extent to which the active substance is affected by varying conditions should be taken into account. Otherwise trials will need to be carried out over two growing seasons.

lxxviii) Where long-term control of a target organism is claimed, then assessment may need to be carried out over a reasonable period as a change in formulation may affect longer term control, e.g. for perennial weeds control in the following year may need to be assessed.

lxxix) Where there are differences between results statistical analysis should normally be carried out, unless such analysis can be shown to be not relevant.

Acceptable levels of product performance

Usually, if these tests show that the effectiveness and the crop safety of the two formulations are the same, then no further tests are required to establish comparability. However, if in most trials the formulations are comparable, but due to adverse conditions, the level of efficacy of both formulations at recommended doses




is below that considered acceptable, this may not in itself be a sufficient demonstration of comparability. In this case, further trials may be required to assess whether the two formulations are still comparable in trials where conditions are such that the ‘old’ product does give the expected level of efficacy.

4.3.3. Further investigation

Where the trials show that the proposed formulation is less effective or less crop safe than the 'old' formulation, data on the 'new' formulation should stand alone. In this case a more detailed examination of its efficacy will then be required. This is likely to include a full range of trials, some taken to yield, so that the label claims are supported by evidence where only the ‘new’ formulation has been used.

4.3.4. Formulations where supporting data are out of protection

In order to access data out of protection for another formulation, comparability trials are required which compare the proposed formulation with the one for which data out of protection are available. As a general rule, the formulation to which bridging is proposed should always be the original formulation which was supported by a full data set and not to any subsequent formulation approved as a minor formulation change, or one supported by limited bridging data.

In some situations, that formulation may no longer be available. As such, direct bridging is not possible. However, provided the applicant conducts trials across a broad and representative range of uses, and the proposed product performs as expected for such a product type, then a reduced data package can be accepted on the basis of the out of protection knowledge that the formulated active substance is effective for the uses sought.

This approach may mean that a rather greater number of trials are required than when bridging directly to an out of protection formulation, particularly if wishing to gain approval for all the original label claims, but still enables a reduced data set compared to the full data set required for a new and protected use to be used. The same principle applies if the trials are conducted outside of the UK where an appropriate non-UK approved product is being used as the standard instead of the UK approved product for which data is out of protection.

Note that if the numbers of trials are limited, the label claims may be restricted to the actual situations (i.e. crop/pest combinations) tested in the trials. In this situation, further data would be needed to add additional pests/crops to the label later.

4.3.5. Other efficacy aspects

Data on some other efficacy aspects, for example, following crops and resistance, are generally taken to be related to the active substance. Therefore formulation comparability evidence is not normally needed to make use of existing data. For many other aspects, the fact that formulation comparability has been established should provide the basis to substantiate that existing data can be used for the new formulation, e.g. dose response, biological compatibility, effects on quality, transformation processes, and plants or plant products to be used for propagation.




● Vapour drift is an important concern when considering effects on adjacent crops. Existing data on this aspect can be used if the applicant can establish, either by way of a reasoned case or tests, that the vapour drift of the 'new' formulation is no greater than that of the ‘old’ formulation.

4.4. Guidance on extrapolation in specific situations

Just as it is often necessary to carry out separate trials for effectiveness and for crop safety, it will usually be necessary to give separate consideration to these two aspects when extrapolation is proposed. The following notes provide more detailed guidance to help applicants to write well reasoned and acceptable cases in each of the specific areas. Please note previous comments under 3.5.4 on development of guidance by EPPO in this area.

4.4.1. Guidance on extrapolations for crop safety

The use of a case based solely on extrapolation as evidence of crop safety will usually only be successful when considering extensions of approval from major to minor crops. However, there are other circumstances where it is appropriate to consider extrapolations for crop safety between major crops or from minor to major crops.

Crop safety can vary considerably between different plant species and between different pesticide products, so before making an extrapolation applicants need to consider both these factors. The following basic questions are a guide to the areas which might need to be considered:

lxxx) Are any of the crops on which the product is already approved related taxonomically to the new crop?

lxxxi) Is the morphology of the crops concerned similar?

lxxxii) Are the growing conditions and uses of the crops similar?

lxxxiii) Is the extrapolation from a major crop(s) to a minor crop?

lxxxiv) Are there adequate crop safety data showing a good margin of safety for the crop(s) from which extrapolation is required?

lxxxv) Is the mode of application (e.g. dose, water volume, timing) the same for the crops involved in the extrapolation?

For some product/crop combinations the answer to all the above questions will be 'yes', in which case there will be a strong case for extrapolation. In some such instances it may be appropriate to make a Qualified Recommendation (see section 3.9.4). A negative answer to one or more of the above questions does not necessarily preclude extrapolation, but should prompt applicants to question the degree to which the extrapolation is valid. In such cases it may be that extrapolation can still provide part of the case for crop safety, with some further data required to confirm its acceptability. Alternatively extrapolation may not be possible, for example: where the product has shown crop damage on some crops; where the crops concerned are significantly different; where the crop is known to be particularly sensitive. In these cases a stand-alone crop safety package will be required.




Applicants should note that when using extrapolation as part of an application for approval, a soundly reasoned argument should be presented in the efficacy overview as to why that extrapolation is considered acceptable. The above list of questions could be used as a basis for such an argued case, with any factors relevant to the particular situation also being taken into account.

4.4.2. Guidance on extrapolations for effectiveness - Diseases

If data show that a fungicide is capable of controlling certain diseases in a number of situations then a case may be accepted that control of the same or a related disease is possible in other situations. For example if data are available showing good control of four species of rusts on ornamentals then it should be possible to extrapolate to other rusts of ornamentals. However the epidemiology of a pathogen and the effectiveness of control agents can be different on different host plants, or even on different parts of the same host plant. For example, Botrytis cinerea has a wide host range, is a wound parasite but can also infect fruits, and on tomato can cause disfigurement of fruits ("ghost spot") without establishing a progressive infection. In such cases extrapolation may not be acceptable.

CRD have previously accepted extrapolations from the following diseases on one crop to the same disease on another crop with no supporting data (see Table 8.6).

Table 8.6: Disease Extrapolations

Disease/pathogen

Extrapolation

Notes From To

Fusarium nivale (Seedling blight)

Winter wheat

Spring wheat

Same pathogen and the test is more severe on W. wheat

Winter barley

Same pathogen and W. barley is less susceptible

Bunt/covered smut

Wheat Barley Similar pathogens; control relies purely on disinfection of spores on the seed surface

Eyespot Winter wheat Winter barley

Spring wheat Spring barley

Same pathogen and similar disease development Same pathogen and similar disease development

Powdery mildew Winter wheat Spring wheat

Same pathogen and similar disease development

Rhynchosporium Winter barley Spring barley

Same pathogen and similar disease development




4.4.3. Guidance on extrapolations for effectiveness - Insects and mites

Depending on how mobile a compound is on a particular plant type and how and where insects or mites feed on a plant their accessibility and hence the effectiveness of a pesticide can vary greatly. Some individual species of pests feed in different places on different crops and this may affect the activity of a product against the same pest on different crops. However, in many cases it is possible to make well-argued extrapolations. It is sometimes possible to make a case that the pest for which approval is sought feeds in a similar way to others for which activity has already been proved.

If data are available showing that an active substance can control a number of species of insects or mites feeding in the same situation on the plant (e.g. on the roots or within leaf mines) then extrapolation is more likely to be accepted. For other pests, it may be possible to argue that the timings of treatment are coincident. However it must be emphasised that the biology of the pest and its location on the plant has to be taken into account.

CRD has previously accepted extrapolations from the following pests on one crop to the same pest on another crop with no supporting data (see Table 8.7).

Table 8.7: Insect and mite extrapolations

Pest species Extrapolation

Notes From To

Two spotted spider mite

Mites on hops, strawberries, and tomatoes

Mites on runner beans and raspberries

Sufficient data should have been acquired during the trials to be confident of extrapolation

Field and laboratory data for Oryzaephilus surinamensis and/or Sitophilus granarius

O. surinamensis and/or S. granarius

Tribolium species and Cryptolestes ferrugineus

Extrapolation is possible if lab. data are available showing similar mortality to O. surinamensis and/or S. granarius and the target pest is likely to receive the same exposure.

For spray applications on leather jackets

Applications on cereals, beet and grass

Other crops e.g. peas, beans and rape

Same species having the same biology on different hosts

Certain caterpillar species

Garden pebble, large white and diamond-back moth

Small white and cabbage moth

Caterpillars are a less challenging target.




4.4.4. Guidance on extrapolations for effectiveness - Weeds

The required level of control of a particular weed and the level that can be achieved by a particular herbicide can be very different in different crops depending on a variety of factors. These factors include competitiveness of the crop, timing of weed control, times of sowing/planting, time/method of harvesting and ease of separating crop seeds and weed seeds. If enough is known about the required levels of weed control, the competitiveness of the crop situation and the factors affecting achievement of those levels in both crops, it would be possible to make a well-argued case for extrapolation from one crop to another. For example, taking competitiveness into account:

Table 8.8: Weed extrapolations

Situation Crops Notes

A - Arable - competitive crops

Cereals, grassland, oilseed rape

Extrapolation accepted within group and from B or C.

B - Arable/horticultural - poorly competitive crops

Sugar beet, peas, onions, linseed, brassicas

Extrapolation accepted within group and from C, but not A.

C - Other situations - non-competitive crops

Orchards, HONS, amenity vegetation, land not intended to bear vegetation

Extrapolation accepted within group but not from A , and possibly from B.

4.4.5. Extrapolation between professional and home/garden products

For information on extrapolation from professional products to use in the home garden, see Efficacy guideline 211.

4.4.6. Further guidance on extrapolation

A guidance document titled ‘Proposal for extending and harmonizing efficacy and crop safety extrapolations to reduce the need for efficacy trials on minor crops’ is available. This document was produced by PSD under a Commission contract. It makes proposals for efficacy extrapolations to facilitate the approval of extensions of use onto minor crops and against minor targets.







4.5. Numbers of trials required for major crops.

Decision making schemes - trials numbers for cereal pests

Figures 8.1-8.3 indicate the number of trials required for major cereal pests, diseases and weeds. The diagrams assume that all the data substantiating the efficacy of a product are from specifically conducted efficacy trials, using recognised methodology (see section 3.9 Conducting field trials), and conducted in situations directly relevant to the proposed use of the product. In all cases this guidance assumes that the results fully support the claims being made.

Oilseed rape and brassicas

Specific advice on oilseed rape and brassicas is presented in Efficacy guideline 405.

4.6. Pest populations required in trials

It is essential that populations of the target organisms (weeds/pests/diseases) in efficacy trials are present at agronomically significant levels in order to provide a sufficient challenge to the treatments applied. In most cases, the size of the pest population present immediately before treatment application will be the most relevant measure of the initial pest challenge. However, in the case of pre-emergence herbicides or fungicides claiming ‘protectant’ activity for example, this information will not be available and the pest levels on untreated plots at later assessment timings will need to be considered instead.

Note that the initial level of the target organism is not the only measure of an adequate pest population. Pest levels on untreated plots must be maintained, or increase, throughout the duration of the trial. Trials where adequate initial pest levels on untreated plots subsequently decline (in the absence of treatment) are unlikely to provide evidence that a sufficient pest challenge existed on the treated plots. [Note however that trials where such a decline occurs may, in some circumstances, be used to provide evidence of crop safety.]

It is not appropriate to have a prescriptive list of ‘minimum populations’ for all possible target organisms but indicative levels for weeds, pests and diseases in various crops are given below. Note that it would normally be expected that at least some trials would be conducted on pest populations much greater than the minimum acceptable population. However, provided the majority of trials within a data-set have above-minimum pest levels, the occasional near-but-below-threshold level should not be considered unacceptable.





4.6.1. Weeds

In general, a minimum population of 5 plants/m2 for each weed species being tested is required for a trial to be considered valid. However, particularly for major weeds such as black-grass or cleavers, some data should be submitted from much greater population levels.

For grass weeds, the definitive assessment will often be the ‘head count’, and in general the minimum acceptable number of tillers in the untreated plots is 20/m². In the case of major grass weeds such a black-grass, ideally some data should be submitted from trials where populations exceed 100 heads/m2.

Overall, trials should cover a range of weed population sizes and should include some large, challenging populations.

4.6.2. Diseases

For most diseases, an incidence of at least 5% plants infected or 5% leaf area infected is the minimum level required. For curative claims this should be the level of infection at application. For preventative claims it will be the level at assessment. In some cases, depending on the pathogen, the assessment methodology and sample size, higher disease levels may be required. For example, diseases of oilseed rape are often assessed on a scale of 1-4 and disease levels must reach at least the second point on such scales, which may be equivalent to 50% infection. For diseases such as potato late blight, measurement of the delay in foliage blight reaching a specific level of infection (usually 25% leaf area affected) would be acceptable. In trials with low levels of infection, there may still be scope to use these data by increasing the sample size assessed and providing a case and justification why the data would be acceptable.

Certain seed-borne diseases on cereals e.g. bunt and smuts, typically occur at very low levels in commercial seed. However use of seed with low infection levels in trials may be acceptable where there is potential for very rapid multiplication of the pathogen and where very high levels of control are required. However, sample size for assessment may need to be increased.

Artificial inoculation of a pathogen may be used to obtain challenging levels of disease. If artificial inoculation is used, the whole trial should be inoculated evenly and a suitable period of time must be allowed to permit disease establishment before treatments are applied. Natural or artificial level of infection of seed lots should be assessed prior to the trial by an appropriate method.

Note that it would not generally be acceptable to have all trials with infections at or close to the minimum level. At least some trials in a series should have infection levels considerably above the minimum.




4.6.3. Pests

Specific agronomic treatment thresholds have been established for many of the main crop/pest combinations. These are widely publicised by advisory organisations and in general these should be viewed as the minimum level for efficacy trials. Where no treatment-threshold exists, the occurrence of agronomic damage on untreated plots may be used to justify the pest population. The majority of trials should be carried out on naturally-occurring pest infestations but artificial introduction may be used to boost pest populations in some trials. Where this is used, sufficient time must be allowed for the introduced individuals to become established before treatments are applied.

Note that it would not generally be acceptable to have all trials with infestations at or close to the minimum level. At least some trials in a series should have infestations considerably above the minimum.

4.7. Information required in support of peripheral label claims

4.7.1. Rainfastness

Examination of this subject has shown that rainfastness is a complex issue. It is affected by a large number of factors such as the type and intensity of the rain, the physical and chemical characteristics of the pesticide, dose, formulation, temperature and relative humidity.

Expert advice is that most pesticides are rainfast within 12 hours. Therefore, it may be possible to support a rainfastness claim of 12 hours or more without data. For claims below 12 hours, data or a case will be required. Consideration will, of course, need to be given as to whether it is appropriate for a rainfastness claim to appear on the product concerned.

4.7.2. Label statements which require no supporting data

In drawing up this guidance the provision of a list of label statements which do not require supporting data was considered. It was concluded that many directions for use, warnings and other pieces of advice may be included on product labels without the need for supporting data. However, to draw up a standard list was felt to be un-necessarily restrictive, not only because it would tie applicants to a standard wording, but also because in some cases the acceptability of such label statements without data varies from product to product.

In drawing up labels applicants are therefore encouraged to consider the basis for each label statement they make (e.g.; a statement may be based on general knowledge for spray applications, on accepted ‘good agricultural practice’ or on data previously submitted for the active substance), and then to clearly explain the basis in the efficacy overview. In many cases it will be possible to justify the use of a label phrase with a very simple statement.




Winter Wheat

Major diseases ~ 10 acceptable trial results:

powdery mildew, brown rust, yellow rust,

Septoria tritici, Septoria nodorum, eyespot,

sharp eyespot, take-all, bunt (seed-borne),

fusarium seedling blight, septoria seedling

blight.

Minor diseases ~ 3 acceptable trial results:

tan spot, ear diseases (sooty moulds, fusarium,

botrytis), bunt (soil-borne ), loose smut,

penicillium blue mould.

Major diseases 10 acceptable trial results:

powdery mildew, brown rust,

rhynchosporium, net blotch, leaf stripe, loose

smut.

Minor diseases 3 acceptable trial results:

eyespot*, take-all*, snow rot, cochliobolus

foot rot.

Claim allowed on basis of extrapolation

from wheat:

yellow rust* (brown rust on barley also

required in support), Fusarium seedling

blight*, covered smut*

* if adequately supported on winter wheat.

Claims for all barley diseases listed above

allowed on basis of extrapolation except:

leaf stripe (10 trials required)

powdery mildew, loose smut (3 confirmatory

trials required)

If adequately supported on winter wheat

and/or barley, claims for all relevant

diseases listed above allowed on basis of

extrapolation except for the following

diseases on oats:

powdery mildew, crown rust, fusarium

seedling blight (3 confirmatory trials required

on each disease).

Winter Barley

Spring Barley

Minor CerealsIncluding; oats,

spring wheat, durum

wheat, rye, triticale.

Yes

Are sufficient

data available on

winter barley?

No

Figure 8.1; Decision-making scheme to determine number of disease control trials required for registration of cereal fungicides.




Figure 8.2; Decision-making scheme to determine number of pest control trials required for registration of cereal insecticides.

Winter Wheat

Major pests 10 acceptable trial results:

summer aphids, slugs, wireworms,

leatherjackets, wheat bulb fly and frit fly.

Minor pests 3 acceptable trial results:

thrips, blossom midges, opomyza and

BYDV vectors*

* if adequately supported on winter barley


BYDV vectors.


summer aphids, slugs, wireworms,

leatherjackets, wheat bulb fly and frit fly.

Minor pests*

thrips, blossom midges and opomyza.

*Claim allowed on basis of extrapolation

from wheat if pest biology and pest/crop

interaction comparable.

Claim for all relevant pests listed above

allowed on basis of extrapolation from

winter wheat/winter barley if pest biology

and pest/crop interaction is comparable.

An example of an unacceptable

extrapolation would be BYDV between

winter and spring crops.

Winter Barley

Minor Cereals Including; oats, spring

wheat and barley,

durum wheat, rye,

triticale.

Yes

Are sufficient

data available on

winter wheat

and/or winter

barley?

Are sufficient data

available on

winter wheat?

No

Yes

No

Note: where different methods or timings of application are proposed (e.g. admixture and broadcasting of slug pellets,

soil application and deadheart spray against wheat bulb fly), each should be fully supported.




Investigate

Herbicidal Activity,

e.g. screens, early

trials

Active against

grass weeds

Major weeds 10 acceptable trial

results:

black-grass ,wild oats, common couch,

barren brome, annual-meadow grass

Other important grasses 5 acceptable

trial results, (3 trials if related species

controlled):

bents, rye-grasses, onion couch, meadow

brome rough meadow-grass

Active against

broad -leaved

weeds

Other broad-leaved weeds ~ 3 acceptable

trial results per species:*

e.g. common chickweed, volunteer oilseed

rape, scentless mayweed, common field-

speedwell, field pansy, common poppy, fat

hen,

If related weeds controlled less trials may

be required

*Activity should be assessed against a

range of broad-leaved weeds on at least 20

sites giving approx. 50 individual results.

Sporadic weed - one result:

A very uncommon weed where related

weeds are well controlled, e.g. thale cress

if other crucifers controlled, fig-leaved

goosefoot if fat hen controlled.

Major weeds ~ 10 acceptable trial

results:

cleavers, volunteer potatoes

Figure 8.3; Decision-making scheme to determine number of weed control trials required for registration of cereal herbicides.




5. Efficacy Guidelines

The guidance above presents general advice for addressing efficacy requirements for approval. More detailed advice is available in the following documents, all of which have been agreed with the efficacy working group of the CPA. A paper copy of any of these is available on request: Further guidelines will be issued from time to time, and an up to date list is maintained on CRDs website at http://www.pesticides.gov.uk/guidance/industries/pesticides/topics/pesticide-approvals/pesticides-registration/data-requirements-handbook/ecotoxicology-and-environmental-fate-working-documents.

NUMBER TITLE NOTES

General guidance on generating data and submitting applications

101 Guidelines for the Preparation of a Biological Assessment Dossier

See also EPPO 1/181

102 Guidance on the Preparation of an Efficacy Overview Historical only use 101

103 Efficacy Requirements for the Re-registration of Products containing Existing Active Substances after Inclusion in Annex I

104 Guidance for Efficacy Sifting of New Active Substance Submissions

110 Official Recognition of Efficacy Testing Organisations

111 Guideline on Statistical Analysis of Efficacy Data See also EPPO 1/152

112 Guidance on Conducting User Trials

113 Requirements for an Efficacy Assessment and Availability of Relevant Guidance

EPPO standard 1/223

114 Guidance on the Status and Use of EPPO Guidelines for the Efficacy Evaluation of Plant Protection Products

115 Guidance on Numbers of Trials in Target Crops for Demonstration of Efficacy and Crop Safety

EPPO standard 1/226

116 Minimum Effective Dose EPPO standard 1/225

117 Groundwater metabolites – guidance on efficacy aspects

http://www.pesticides.gov.uk/guidance/industries/pesticides/topics/pesticide-approvals/pesticides-registration/data-requirements-handbook/ecotoxicology-and-environmental-fate-working-documents






http://www.pesticides.gov.uk/Migrated-Resources/Documents/G/G103.pdf


















NUMBER TITLE NOTES

Application or situation specific guidelines

201 Fabric Treatments with Residual Insecticides

202 Fumigants for the Control of Insect and Mite Pests of Stored Products

203 Pesticides for Admixture with Stored Cereals to Control Insects and Mites

204 Space Treatments - Against Flying Insects

205 Larvicides in Animal Rearing Units

206 Baits for the Control of Houseflies in Animal Rearing Units

207 Hand Held Aerosols and Ready for Use Sprays Against Crawling Insects

208 Seed Treatments - Efficacy and Physical/Mechanical Data Requirements

209 Propagule Fungicide/Insecticide Treatments Data Requirements - Efficacy and Physical/Mechanical Data Requirements

210 Simulation of Aerial Application to Field Crops Using Ground Based Sprayers

211 Efficacy Data Requirements for Home Garden Products

220 Data Requirements and Trials Design for Mating Disruption Pheromone Products

Crop Safety Guidelines

301 Guidance on Taint Testing Superseded by EPPO 1/242

302 Cleaning Application Equipment – Efficacy Aspects

303 Effects on Non-Target Crops of Highly Active Herbicides - Including Mixtures and Sequences

304 Transformation processes Superseded by EPPO 1/243

305 Cleaning Application Equipment – Small scale jar test protocol

306 Plant parts for propagation Incorporated in EPPO 1/135

307 Quality Parameters - Cereals Crop Specific Guidelines

401 Efficacy Testing of Apple and Pear Fungicides and Insecticides in the UK

402 Guidance Document on the Trials Requirements for a Potato Haulm Desiccant

403 Provision of Information on Tree Canopy Size in Efficacy and Residue Trials in Apple Orchards

404 Data Requirements for PGR Products in Pome Fruit (pre-harvest, post harvest and ‘in store’ applications)

405 Data Requirements for Oilseed Rape and Brassica Pests, Diseases and Weeds

406 Data Requirements for Turf Fungicides, Herbicides, Insecticides and Plant Growth Regulators

Pest/Disease/Weed specific Guidelines

510 Evaluation of Molluscicides

530 Requirements for a New Late Blight Fungicide for Potatoes

590 Guidelines on Efficacy Tests for Rodenticides Available on request

591 Guidelines on Efficacy Testing of Mammal and Bird Repellents

592 Requirements for Products used for Mole Control








































http://www.pesticides.gov.uk/Migrated-Resources/Documents/E/Efficacy_Guideline_510_Evaluation_of_Molluscicide_Products.pdf


http://www.pesticides.gov.uk/guidance/industries/pesticides/topics/pesticide-approvals/pesticides-registration/efficacy-guides/guidelines-on-the-generation-of-efficacy-data






NUMBER TITLE NOTES

Chemical and Control Specific Guidelines

601 Resistance Warnings on Labels of Insecticide and Acaricide Products.

602 Resistance Warnings and Restrictions on Labels of Professional Herbicide Products

603 Fungicide Resistance Label Advice and Restrictions

604 Efficacy Data Required For Tank Mixtures and Sequences of Pesticides

606 Resistance Risk Analysis and use of Resistance Management Strategies

See also EPPO 1/213

607 Insecticide Mixtures: Justification for Use and Implications for Resistance Management in the United Kingdom

608 Using Non-toxic Slug Traps when Assessing Slug Activity and the Risk of Damage in Winter Wheat and Oilseed Rape

611 Guidance on the Restriction of Use of High Resistance Risk Herbicides

630 Data Requirements for Aqueous Dispersions of Sulphur












http://www.pesticides.gov.uk/Migrated-Resources/Documents/E/Efficacy_Guideline_608_Using_Non_Toxic_Slug_Traps.pdf

http://www.pesticides.gov.uk/Migrated-Resources/Documents/E/Efficacy_Guideline_608_Using_Non_Toxic_Slug_Traps.pdf


