EPAA Annual Conference Regulatory acceptance and implementation of 3Rs approaches Plant protection products Patricia Brunko European Commission - DG SANCO Unit E3 – Chemicals, contaminants and pesticides 5 November 2007

DIRECTIVE 91/414/EEC Approval of active substances at EU levelApproval of active substances at EU level Authorisation of plant protection products at Member State levelAuthorisation of plant protection products at Member State level Harmonised DATA REQUIREMENTS Currently under revisionCurrently under revision Annex II / Annex IIIAnnex II / Annex III Physical and chemical properties (Dir 94/37/EC) Physical and chemical properties (Dir 94/37/EC) Analytical methods (Dir 94/46/EC) Analytical methods (Dir 94/46/EC) Efficacy data (Dir 93/71/EC) Efficacy data (Dir 93/71/EC) Toxicogical studies (Dir 94/79/EC) Toxicogical studies (Dir 94/79/EC) Residues in or on treated products, food and feed (Dir 96/68/EC) Residues in or on treated products, food and feed (Dir 96/68/EC) Fate and behaviour in the environment (Dir 95/36/EC) Fate and behaviour in the environment (Dir 95/36/EC) Ecotoxicological studies (Dir 96/12/EC) Ecotoxicological studies (Dir 96/12/EC)

PROPOSAL FOR A NEW REGULATION Will replace Directive 91/414/EEC Will incorporate data requirements of Directive 91/414/EEC Will incorporate data requirements of Directive 91/414/EEC Currently under co-decision procedure Currently under co-decision procedure

PROPOSAL FOR A REGULATION replacing Directive 91/414/EEC Implementation of 3Rs approaches PROHIBITION OF DUPLICATIVE VERTEBRATE TESTING PROMOTION OF ALTERNATIVE TESTING

PROPOSAL FOR A REGULATION replacing Directive 91/414/EEC Rules should be laid down to avoid duplication of tests and studies. In particular, repetition of studies involving vertebrates should be prohibited. There should be an obligation to allow access to studies on vertebrates.Rules should be laid down to avoid duplication of tests and studies. In particular, repetition of studies involving vertebrates should be prohibited. There should be an obligation to allow access to studies on vertebrates. To allow operators to know what studies have been carried out by others, EFSA makes summary dossier available + Member States keep a list of such studies.To allow operators to know what studies have been carried out by others, EFSA makes summary dossier available + Member States keep a list of such studies. PROHIBITION OF DUPLICATIVE VERTEBRATE TESTING Recital 32 + Art Art Art. 59

PROPOSAL FOR A REGULATION replacing Directive 91/414/EEC PROHIBITION OF DUPLICATIVE VERTEBRATE TESTING Article 59 - Sharing of tests and studies involving vertebrate animals Tests and studies involving vertebrate animals shall not be repeated.Tests and studies involving vertebrate animals shall not be repeated. Industry:Industry: Before undertaking tests and studies, verify that they have not already been performed or initiated. Before undertaking tests and studies, verify that they have not already been performed or initiated. Every effort to share tests and studies involving vertebrate animals. Every effort to share tests and studies involving vertebrate animals. Inform competent authorities, if no agreement for test sharing. Inform competent authorities, if no agreement for test sharing. Competent authorities:Competent authorities: Shall use the already available tests and studies. Shall use the already available tests and studies. National Courts to determine the costs to be shared.National Courts to determine the costs to be shared.

PROPOSAL FOR A REGULATION replacing Directive 91/414/EEC PROMOTION OF ALTERNATIVE TESTING In order to avoid animal testing, testing on vertebrate animals for the purposes of this Regulation should be undertaken only as a last resort. This Regulation, and the legislation establishing data requirements for active substances, plant protection products, safeners and synergists, should ensure that testing on vertebrate animals is minimised and that double-testing is avoided, and promote the use of non-animal test methods and intelligent testing strategies. EP amendment for an additional recital On-going revision of data requirements in line with this objective

PROPOSAL FOR A REGULATION replacing Directive 91/414/EEC PROMOTION OF ALTERNATIVE TESTING The summary dossier shall include the following: […] […] for each test or study involving vertebrate animals, a justification of the steps taken to avoid animal testing and duplicative testing on vertebrate animals. for each test or study involving vertebrate animals, a justification of the steps taken to avoid animal testing and duplicative testing on vertebrate animals. EP amendment for additional requirement in Art 8 (Dossiers)

Revision of data requirements of Directive 91/414/EEC Drafts developed from 2002 in close consultation with Member States and industry Drafts developed from 2002 in close consultation with Member States and industry EFSA opinion EFSA opinion Revision Revision One single directive for all sections One single directive for all sections New data requirements to be transferred into new Regulation New data requirements to be transferred into new Regulation

Revision of data requirements of Directive 91/414/EEC Implementation of 3Rs approaches TIERED APPROACH/ DELETION PROMOTION OF ALTERNATIVE TESTING AVOID REPETITION OF ANIMAL TESTING

PROMOTION OF ALTERNATIVE TESTING Toxicology section (draft May 2007) Revision of data requirements of Directive 91/414/EEC non-test methods reduction and refinement methods reduction and refinement methods Tests on animals to be undertaken only where no other alternatives are possibleTests on animals to be undertaken only where no other alternatives are possible When no alternatives are available, other appropriate testing strategies shall be used to keep the number of animals used to a minimum. These include:When no alternatives are available, other appropriate testing strategies shall be used to keep the number of animals used to a minimum. These include:

AVOID REPETITION OF ANIMAL TESTING Toxicology section (draft May 2007) Studies conducted in the past, although not fully compliant with todays standards and GLP, may be integrated into the assessment, if scientifically valid, thereby removing the need for repeating animal tests, especially for carcinogenicity and reprotoxicity studies. Revision of data requirements of Directive 91/414/EEC

Toxicology section (draft May 2007) Tiered approach applied throughout the sectionTiered approach applied throughout the section Revision of data requirements of Directive 91/414/EEC Deletion/replacement of studies:Deletion/replacement of studies: Short term toxicity: deletion of the 1-Year dog studyShort term toxicity: deletion of the 1-Year dog study Genotoxicity: deletion of the rodent dominant lethal assayGenotoxicity: deletion of the rodent dominant lethal assay Multi-generation studies: F1-extended one generation study to be considered as alternative approach to multi-generation study as soon as developed and validated.Multi-generation studies: F1-extended one generation study to be considered as alternative approach to multi-generation study as soon as developed and validated. TIERED APPROACH/ DELETION

CONCLUSION Replacement by regulatory acceptance of alternative methods Replacement by regulatory acceptance of alternative methods+ Reduction and Refinement by prohibition of duplicative vertebrate testing + testing strategy Reduction and Refinement by prohibition of duplicative vertebrate testing + testing strategy Proposal for a Regulation replacing Directive 91/414/EEC Draft Data requirements to Directive 91/414/EEC