How many field trials should be conducted when register a pesticide in Europe?

Date:12-19-2012

The European Union exists as a single market for most common commodities. For Plant Protection Products (PPPs) it is not a single market but does have a single principle for access to selling PPPs – the approval scheme. For PPPs there is a single European regulation for the approval of PPPs.

Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC

The Regulation follows the previous Council Directive¹  which was repealed at the time of the above regulation was published. The regulation was first published in November 24th, 2009, and it entered into force later the same year. It became applicable to be used in all European member states from June 14th, 2011. It retains many of the central principles of the previous directive.

This Regulation provides the single overlying requirement for approval before sales. To achieve an approval to place a PPP on the European market, a dossier has to be presented with the basic laboratory, safety and in-use data. Most of this data can be generated inside or alternatively outside Europe in other OECD accepted GLP facilities; however field trials must be conducted in Europe in clearly defined geographic zones. These are the only tests that must be done in the geographic boundaries of Europe. In practice field trials are done in 1) the country where you make the first application for approval and 2) countries where you are likely to register in the future. This article will explain how many field trials should be conducted and where they should be done.

Where to conduct trials?

In principle you need to consider that there are 3 regional maps before you organize field trials:

1) It is important for registration purpose of PPPs to consider the Rapporteurs are grouped in 3 zones² . There is a mutual acceptance policy between countries in the same zone.

● North – Denmark, Estonia, Latvia, Lithuania, Finland, Sweden
● Central – Belgium, Czech Republic, Germany, Ireland, Luxembourg, Hungary, Netherlands, Austria, Poland, Romania, Slovenia, Slovakia, United Kingdom
● South – Bulgaria, Greece, Spain, France, Italy, Cyprus, Malta, Portugal

2) Residue trials are conducted in 2 zones including north and south:

● Northern and Central Europe:
   ○ Sweden, Norway, Iceland Finland, Denmark, United Kingdom, Ireland, Northern France, Belgium, The Netherlands, Luxembourg, Germany, Poland, Czech Republic, Slovakia, Austria, Hungary, Switzerland, Estonia, Latvia, Lithuania, Romania, Slovenia.

● Southern Europe and the Mediterranean:
    ○ Spain, Portugal, Southern France, Italy, Greece, Malta, Croatia, Serbia, Bosnia and Herzegovina, FYROM (Former Yugoslav Republic of Macedonia), Turkey, Bulgaria, Cyprus
 
3) Efficacy and selectivity trials are conducted in 4 zones including:

● Maritime
● Mediterranean
● North-East
● South-East

This can be complicated; the initial objective of the European Union was in principle for an open market, and one of the specific objectives was making registration simpler. If anything the organization of field trials is more complicated depending on market strategy, and placement of field trials.

The Number of Field Trials - Country Guidance

There are 2 basic types of field trials
● residue trials
● efficacy trials

The guidelines of the specific field trials tests are available in various documents and summarized as:

Efficacy Guidelines
● Local Country Pesticide control agencies
    ○ For example see www.pesticides.gov.uk which will provide guidance for trials in Great Britain. There are other national agencies that will provide local guidance.
● EPPO³
    ○ an international agency for the purpose of consistency in field trials (efficacy)

Residue Guidelines
● OECD⁴
    ○ an international agency for the purpose of consistency and guidance in field trials (residue studies for assessment of MRLs)
● SANCO⁵
    ○ A European agency for protection of the consumer
● FAO⁶
    ○ International agency working for safe food

The Number of Field Trials – Residue Studies

The number of trials for residues is defined in the regulations:

Commission of the European Communities, Directorate General for Agriculture, 7029/VI/95 rev.5, VI B II-1 Appendix B, General Recommendations for the Design, Preparation and Realization of Residue Trials

Major Crops - The minimum requirement is 8 field trials⁷ over 2 years in the major crop⁸ and in the appropriate zone⁹.

Reduction of trial numbers
● If the supporting data is available to show residues will be low and lower than the limit of determination for the analytical method.
● If there is likely to be consistency between sites

Minor Crops - The minimum requirement is 4 field trials over 2 years in the minor crops¹⁰ and in the range of likely territories.

The required number of field trials – Efficacy and selectivity

The number of trials for efficacy is explained in the regulations: EPPO Guidance 1/226, Number of Efficacy Trials

The requirement is 10 trials over 2 years in the major crop and in the appropriate zones, but may vary depending on:
● Overall importance of the crop and pest
● Severity of the damage
● Cultivar effects
● Impact of soil and climatic effects
● Prior knowledge of the active substance or product
● General consistency

The trials will be considered effective if they are:
● Conducted over the range of environmental and climatic conditions
● Have been effective against controlling the pest compared to controls and reference products
● Conducted against challenging pest attacks
● Results are consistent

Trial numbers may be reduced if:
● Large number of supporting evidence
● Crop or pest are of minor importance
● Little climatic variation (in grain stores 6 can be accepted)
● Where there is difficult to conduct the trials

In Summary

The European approval system when applied to field trials is complicated and requires expert opinion.  The location of trials is difficult to interpret because of differences in zones and in finding appropriate crops with pests.

The key underlying requirements are:
● preliminary discussions with regulatory agencies
● talk to experts before embarking on a program of field trials

This is my own personal recommendation

Do a little more than the basics, field trials can often suffer from destructive weather and from non-appearance of pests (essential for efficacy studies). You may complete your two year studies and find you have less than the acceptable number of trials for evaluation. I suggest you should always add extra trials to ensure you have sufficient after two years. It can be an expensive mistake to return to the fields for a third year to complete. Saving a little money at the beginning can end with you paying more with loss in revenue from missing the market.

Annotations:
¹  Council Directive of 15th July 1991 concerning the placing of Plant Protection Products on the market (91/414/EEC).
² Regulation 1107/2009; concerning placing of plant protection products on the market
³  European and Mediterranean Plant Protection Organisation 
⁴  Organisation for Economic Co-operation and Development
⁵  European Directorate-General for Health and Consumers
⁶  United Nations Food and Agriculture Organisation
⁷  Up to 4 of the trials may need to be decline studies if a significant part of the produce is available for consumption.
⁸  Major refers to crops grown in large quantities.
⁹  Zone – these are summarised in the introduction, however there is a strong recommendation to conduct studies in the country where you first apply and other countries where you intend to market.
¹⁰  Minor refers to crops grown in small quantities or for a specific and minor use