1. Why haven’t we achieved efficacy harmonisation? Peter Schlotter On behalf of ECPA-EffEG Crop Protection European Regulatory Conference – Pre-conference Workshop Efficacy submission in the EU, Brussels 11 th March 2015

2. COMPLEXITY in the EU! 2

3. Introduction and Zonal Process Barriers of harmonisation Approaches taken toward harmonisation under 1107/2009 –Areas for improvements –Remaining challenges Way forward: recommendations for harmonisation by ECPA-EffEG 3 Why haven’t we achieved efficacy harmonisation?

4. THE COMPLEX ZONAL PROCESS – Registration of products All pesticide products must be registered in a country before they can be advertised, sold or used  Following Annex I Inclusion (91/414) or Approval (1107/2009) of the active substance the product must be (re)-registered Before 91/414 (1993): registration acc. national laws in all 28 countries –Last Annex Is under 91/414 were 2011 = many products in Europe registered under old national rules 91/414 Introduction of mutual recognition and voluntary worksharing (came in gradually). dRR format concept started –Efficacy driven by BAD within MSs, other sections already EU or Zonal processes 1107/2009 (06/2011) Zonal process with 3 Administration Zones 4

5. THE COMPLEX Zonal Process – The Zones North (6) –Denmark, Estonia, Latvia, Lithuania, Finland, Sweden Central (13) –Belgium, Czech Republic, Germany, Ireland, Luxembourg, Hungary, Netherlands, Austria, Poland, Romania, Slovenia, Slovakia, United Kingdom South (9) –Bulgaria, Greece, Spain, France, Italy, Cyprus, Malta, Portugal, Croatia Protected uses and seedtreatment –All zones 5

6. Biological development in Europe (Administrative vs EPPO zones) Northern- 6 MS 2 EPPO Zone DNK SWE FIN LIT LVA EST GBR FRA IRL BEL NLD GER CZE SVK HUN ROU AUT POL ESP PRT GRC MLT ITA BGR LUX SVN CYP Southern- 9 MS 3 EPPO Zone Central – 13 MS 3 EPPO Zone 6

7. European map with defined geographic regions: 4 EPPO Climatic Zones (in colour) and 3 European Administration Zones Kroatien Note: Indoor use = one Administration Zone Trend for more systematic use of PP1/241 in designing, implementing and reporting on trial programs. Trials placed according to relative importance within EPPO zones. 7

8. Barriers of harmonisation Complex Process and Zonal structure 8

9. –Implementation of Administrative and EPPO Zones –Central Zone most critical Zone with 3 EPPO Zones (diversity) –Southern Zone with 3 EPPO Zones (France and Croatia with 2) –Communication within the Zone – Language is a barrier 28 countries with 24 official languages (linguistic diversity) –Expansion of European Union to 28 countries 2004: CY, CZ, EE, HU, LV, LT, MT, PL, Sl and SK 2007: BU and RO 2013: HR 13 MSs joined EU more than a decade after 91/414 –National registrations and requirements Barriers of harmonisation 1 Complex Process and Zonal structure 9

10. –EPPO and Guidelines Documents (GD) Interpretation of guidelines Not all MSs are following EPPOs and GDs –dRR and BAD No agreed zonal standard or template available Misunderstanding content and role of BAD and dRR Efficacy the only section with 2 dossiers + single field trial reports –Trials and trial reporting and quality Acceptance of old data reports and country registrations – Data requirements - Number of trials required EPPO PP1/226, but also national guidelines (IT, IR, GR, SK,…) DE – number of trials on each BL weed species required Various requirements without considering EU expansion 10 Barriers of harmonisation 2 Complex Process and Zonal structure

11. –EPPO PP1/226 Definition of major crops, minor crops, major uses and minor crop Minor uses not adapted to Zonal context –GEP certification + Certificates Not all institutes are GEP certified (also Official Institutes !) –Harmonisation of GAPs –Dose rate expression in 3 D crops –Authorities and efficacy evaluators Workload Diverse knowledge of efficacy evaluators within countries and Zone Level of participation of evaluators in committees and conferences Lack of trust leading to repeating evaluation 11 Barriers of harmonisation 3 Complex Process and Zonal structure

12. –Approaches taken towards harmonisation under 1107/2009 –Areas for improvements –Remaining challenges 12

13. Part A – National Risk Management Part B - Core assessment for the zone –Section 1 - identity, phys-chem, further info –Section 2 – methods –Section 3 – tox –Section 4 – residues –Section 5 – EFate –Section 6 – Ecotox –Section 7 – Efficacy will become section 3 (Beginning 2016) –National addenda to any section 1-7 Part C – Confidential Parts A and B may be released to 3 rd parties after authorisation! Approaches taken towards harmonisation under 1107/2009: dRR 13

14. Relationship between draft Registration Report (dRR) and zonal BAD (Part B, section 7 new 3) Process to transform documents of the efficacy package into a registration report (RR). Source: Technical Guidance Paper dRR 14

15. –The Zonal BAD is a detailed analysis of the overall trial work which considers the PPP in relation to its benefits and risks within a specific Administrative zone It’s a complex dossier The Zonal BAD can cover many countries & situations It can cover a multitude of uses (crops, targets) with possibly different GAPs –The Zonal dRR is considered a stand-alone concise summary of the Zonal BAD It is a sizeable summarization of the relevant zonal information 15 Approaches taken towards harmonisation under 1107/2009

16. Approaches taken towards harmonisation under 1107/2009: New dRR table of content 16

17. Finalisation of a new dRR format for future submissions: –The new dRR will be named as Section 3 and contain a new and more organised Table of Content Improved clarity of the different chapters of the dossier Benefits are presented followed by the potential risks of the PPP to: –The crop –Other parts than the crop –Chapter 3.0 is added at the beginning to report on the summary & conclusion from the zRMS associated to a GAP table with recommendations –Commenting boxes seen valuable as soon as initial dRR is a good document 17 Approaches taken towards harmonisation under 1107/2009: New dRR

18. Conducting the needed experimentation and reporting of the data under a dossier format is to be done following EPPO standards: –A set of general standards (26) and efficacy standards (>200) is available –New additional standards are under preparation to complete the needs  This allows using a common language,  that is deemed to follow the Uniform Principles and,  should facilitate possible Mutual Recognitions,  within and between Administrative Zones.  But we see real differences in the use and interpretation of the guidelines  Need to adjust the EPPOs to the Zonal process, PP1/226... Areas for improvements: The EPPO standards 18

19. GEP accredited organisations are allowed to conduct experimentation that is needed for a submission for registration Few exceptions are accepted:  Official Scientific Institutes are sometimes not GEP.  For historical reasons, reports from experimentation conducted in countries prior to GEP implementation can be used and should be accepted. GEP certificates from the Testing Organisations are submitted together with the Biology Assessment Dossier. GEP certificates are documents under diverse formats and in local languages. To ease the use of these documents, ECPA has created an internet database that collects these documents. Areas for improvements: The GEP certification 19

20. Currently 1185 certificates, 675 organisations and 427 registered users across EU Entry of new certificates is checked to avoid duplication of certificates No limitation on access to the database – evaluators do not need to be registered users Open to applicants, regulators, official testing organisations - visible to all EU GEP Certificate Database developed by ECPA EffEG www.gepcertibase.eu A table containing a list of certificates with hyperlinks to certificates, can be downloaded and copied/pasted into dossiers – no need to insert paper copies of certificates – not accepted by all MS 20 BE project to develop a standardized format following the ECPA proposal

21. –Trials should be implemented under GEP accreditation (where established) –Trials should be conducted according to EPPO standards According to the general standards PP1/152, PP1/135, PP1/181, PP1/225,… As well as specific efficacy standards (PP1/XXX) – Trial reports should be of good quality It is recognised that format of trial reports is varied with increasing use of electronic data capture Flexibility by MS of acceptance of old data reports and trial format New trial reports will comply with PP1/181 Areas for improvements: The studies (Trials,…) 21

22. From Official documentations: –EPPO PP1/226 (major pest on major crop, major pest in protected conditions, minor use) –Northern Zone Guidance document with major crops as appendix good example of MS working together (authorities and industry) –National requirements (IT, IR, GR, FR, SK...). Risk of adding complexity to be considered while producing additional documents/requirements  Need for revision of PP1/226 within the frame of Zonal development  Can we get harmonisation without National requirements?  Establishment of a Zonal working group or round table (e.g. Northern Zone)? Remaining challenges: Trial requirements : 22

23. Ireland 2013: Guideline Requirements for Irish based trials on wet weather fungal diseases for Efficacy Submissions in the Biological Dossier to PRCD in relation to the authorisation of a PPP. Slovakia 1/2014 (UKSUP): Metodicky pokyn Number of trials to be submitted in SK France: CEB, Document technique N° 23, Recommandations pour une surveillance de la résistance aux fongicides en vigne Greece 2013: National guidelines, Supplementary to EPPO Standards, Appendix II and III Italy 2015: Studi di efficacia e selettività necessari revisione Ferrero_1.proporta 23 Areas for improvements: National guidance documents

24. Within the submission of a Zonal dossier it looks more efficient to claim for Minor uses across countries despite minor uses are still under National regulation –Status of minor crops differ in different countries –Group of targets: some countries authorize pest group, others single pests Efficacy – different interpretations from Authorities make the Zonal submission critical What about the value of the EUMUDA database? Can we seek for common principles? Revisit the Extrapolation guidelineswithin the frame of Zonal development? Remaining challenges: Minor uses 24

25. Will become the highest workload for both applicants + authorities in the next 3-4 years. Only a light dRR (no BAD) is needed with following assumptions*: –GAPs remained unchanged –No new uses ! No new MS! No formulation change! Update the following items: –Overview of the country registrations and uses and the GAP –Update Resistance section –No new efficacy trials to be submitted Agreement is valid for CZ submissions This process is not yet agreed for SZ 25 Remaining challenges: Re-registration article 43 of 1107/2009 *C. Prohaska, Head of AGES: Informa meeting, Berlin Feb. 2015

26. Dose rate expression in 3D crops is progressing: the LWA concept –Key benefits: Single and scientifically more accurate dose rate expression across Europe Applicable for wall-shaped canopy crops Experienced and agreed by Companies through Working Group activities –Agreed for experimentation for pome fruit trees –Under progress for stone fruit trees and high growing vegetables –Under evaluation for grapes BE has already introduced LWA in 3 D crops DE is planning the introduction in grapes 2016 AT is supporting LWA concept Harmonisation in Europe and in the Zone is needed – Acceptance of previous trials and data sets Remaining challenges: Dose rate expression and standardization 26

27. ECPA Efficacy Expert Group Way forward: Recommendations for harmonisation 27

28. Improve level of trust Communication and cooperation within MS evaluators and industries and within the Zones –Develop pragmatic (Zonal) approaches that have a wide acceptance from MS and industry (round tables, workshops…) –Example Northern Zone guidance on efficacy More flexibility by MSs in regard of acceptance of old data or previous registrations without submission of new data Improve Zonal harmonization in the evaluation –Stop specific national requirements –Development of harmonized Zonal documents – Light dRR for re-registration for all Zones (article 43 of 1107/2009) ECPA EffEG Recommendations for harmonisation 28

29. Implementation and use of the new dRR template Communication zMS evaluators and industry – e.g. pre-submission and follow up meetings Improve Zonal process – time and re-evaluation by cMS after Zonal approval by zRMS Field trial report format + quality – acceptance of older reports and format for re-registration Use of GEP certificate database Follow guidance documents and use of EPPO standards –Revision of EPPO 226: Number of trials for major and minor use – (linkage 226-278-241, better definition of minor uses) Zonal harmonization of expression rates for 3 D crops ECPA EffEG Recommendations for harmonisation 29

30. Why haven’t we achieved efficacy harmonisation? 30 Complexity … Improvements achieved Promotion of harmonisation is needed among all stakeholders in the future

31. Peter Schlotter on behalf of ECPA EffEG Office: +49 45533126; Mobile: +49 171 2445705; pschlotter@dow.com Dow AgroSciences GmbH Truderingerstr. 15 D-81677 Munich Thank you