TECHNICAL REPORT OF EFSA

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1 Supporting Publications 2011:125 TECHNICAL REPORT OF EFSA Outcome of Public Consultation on the draft on Submission of scientific peer-reviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/2009 1, 2 SUMMARY European Food Safety Authority 3, 4 European Food Safety Authority (EFSA), Parma, Italy The European Food Safety Authority (EFSA) carried out a public consultation to receive input from the scientific community and all interested parties on the draft on Submission of scientific peerreviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/2009. The was developed by a working group formed by EFSA external experts and EFSA staff from the Assessment Methodology Unit and the Unit on Pesticide Risk Assessment Peer Review. It provides instructions to applicants submitting dossiers for the approval of active substances of plant protection products on how to identify and select scientific peer-reviewed open literature as required by Article 8(5) of Regulation (EC) No 1107/2009 and how to report the results of the search and the selection of scientific peer-reviewed open literature in a dossier. The public consultation was held to obtain input from stakeholders about the new proposals included in the draft. It was open from 23 July to 15 October This Technical Report presents the comments received through the public consultation, an overview of the most frequent issues raised about the draft, and EFSA s responses to the comments from stakeholders. EFSA received 65 comments from 16 interested parties (individuals, non-governmental organisations, industry organisations and national assessment bodies). EFSA wishes to thank all stakeholders for their contributions. All comments received were assessed by the EFSA working group and the was revised to account for relevant and fundamental issues raised by the stakeholders. Comments referred mainly to: the proposed inclusion of non-peer reviewed open literature in the dossiers; the increased workload that the would pose to the applicants; the identification of the information sources that should be searched; the method for defining relevance criteria for inclusion of studies; and the assessment of the reliability of the studies included in the dossiers and in the risk assessment process. A list of all the original comments explaining how they were addressed by EFSA is reported as an appendix to this Technical Report. KEY WORDS Guidance, scientific peer-reviewed literature, pesticide active substances, dossier. 1 Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October 2009 concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. OJ L 309, , p On request from EFSA, Question No EFSA-Q , issued on 24 February Correspondence: AMU@efsa.europa.eu 4 Acknowledgement: EFSA wishes to thank the members of the Working Group on on Submission of scientific peer-reviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/2009 for the work on this Technical Report: Geoff Frampton (Rapporteur) and Julie Glanville and EFSA staff: Elisa Aiassa, José Oriol Magrans and Laura Ciccolallo. Suggested citation: European Food Safety Authority; Outcome of Public Consultation on the draft on Submission of scientific peer-reviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/2009 (OJ L 309, , p. 1.). Supporting Publications 2011:125. [56 pp] Supporting Publications 2011:125

2 Public Consultation on the draft on Submission of scientific peer-reviewed open literature under Regulation (EC) No 1107/2009 TABLE OF CONTENTS Summary... 1 Key words... 1 Table of contents... 2 Background Introduction Most frequent comments received EFSA consideration of the most frequently raised issues... 5 Appendix 1 Public consultation announcement... 7 Appendix 2 Full list of comments and related EFSA replies... 8 Supporting Publications 2011:125 2

3 Public Consultation on the draft on Submission of scientific peer-reviewed open literature under Regulation (EC) No 1107/2009 BACKGROUND Article 8(5) of Regulation (EC) No 1107/ states that applicants submitting dossiers for the approval of active substances of plant protection products shall provide Scientific peer-reviewed open literature, [ ], on the active substance and its relevant metabolites dealing with side-effects on health, the environment and non-target species and published within the last ten years before the date of submission of the dossier as determined by the European Food Safety Authority (EFSA). To comply with the requirements of Article 8(5) of Regulation (EC) No 1107/2009, the Assessment Methodology Unit (AMU) of EFSA was requested to produce, in collaboration with the Unit on Pesticide Risk Assessment Peer Review (PRAPeR), an on how to identify and select scientific peer-reviewed open literature to inform the dossiers on active substances and how to report the results of the searches and the selection of the literature. For the development of this, AMU established a working group of EFSA external members and EFSA staff. After three working group meetings a first draft of the was completed by the working group on the 20th April 2010 and was submitted to the EFSA Panel on Plant Protection Products and their Residues (PPR) and the Pesticide Steering Committee (PSC). The feedback from both groups of experts was considered by the working group during a meeting and was used to produce a second draft of the. In line with EFSA principles of openness and transparency and in order for EFSA to receive comments from the scientific community and stakeholders on its work, EFSA launched a public consultation on the draft, which lasted from 23 July to 15 October, EFSA was committed to publish the comments received and provide a short Technical Report on the outcome of the consultation. 5 OJ L 309, , p. 1. Supporting Publications 2011:125 3

4 Public Consultation on the draft on Submission of scientific peer-reviewed open literature under Regulation (EC) No 1107/ Introduction During the public consultation held from 23 July to 15 October 2010, sixteen interested parties (individuals, non-governmental organisations, industry organisations and national assessment bodies) provided comments on the draft on Submission of scientific peer-reviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/2009, with a total of sixty-five submissions. A summary of all comments received is given in Table 1 and Table 2. The comments received were scrutinised by the EFSA working group, who provided a specific reply to each of them. All comments and related EFSA replies were tabulated with reference to the author(s) and the section of the draft to which the comment referred and reported in Appendix 2 to this Technical Report. In general the comments were constructive and helped to finalise the. When relevant and fundamental, the comments were taken into account and the was revised accordingly. The EFSA working group wishes to thank the stakeholders for their contributions. This Technical Report summarises the most frequent comments received and the responses provided by the EFSA working group. Table 1. Comments on the draft, ordered by Chapters Number of comments Abstract 7 Summary 4 Background as provided by EFSA 1 Terms of reference as provided by EFSA 2 1. Approach to the mandate 2 2. Intended users of the Guidance 1 3. Introduction - 4. Interpretation and application of terminology employed in Article 8(5) of Regulation (EC) No 1107/ Requirements for identifying and selecting scientific literature to be incorporated into the EU dossiers of active substance of plant protection products Clarify a priori the objective of the review of the scientific literature and set the criteria for study relevance to the dossier Search for scientific literature Identify sources of scientific literature Develop appropriate search strategies Use of reference management software to manage the records of scientific literature Clearly document the search and its results Select relevant studies for inclusion in the dossier Evaluation and use of the included scientific literature in the dossier 7 6. How to present in the dossier the methods and the results of the searches of the scientific literature 3 Recommendations for future research 2 Appendix A - Example of a search for scientific literature for a specific active substance 3 Total number of comments 65 Supporting Publications 2011:125 4

5 Public Consultation on the draft on Submission of scientific peer-reviewed open literature under Regulation (EC) No 1107/2009 Table 2. Comments on the draft, ordered by organisation and country Organisation Country Number European Crop Protection Agency (ECPA) BEL 16 PAN-Europe BEL 5 BfR DEU 4 Federal Environment Agency DEU 3 German Federal Environment Agency DEU 1 Independent Consultant DEU 1 Ministerio de Sanidad y Politica Social ESP 1 Finnish Environment Institute FIN 3 Ministère de l'alimentation, de l'agriculture et de la pêche FRA 1 Chemicals Regulation Directorate GBR 6 JSC GBR 8 CBC Europe Ltd ITA 6 International Centre for Pesticides and Health Risk Prevention ITA 7 Independent Consultant ITA 1 Ctgb Board for the Authorisation of Plant Protection Products and Biocides NLD 1 Royal Institute of Technology, Stockholm SWE 1 Total number of comments Most frequent comments received The issues of the draft that were commented on most frequently by the stakeholders were: The inclusion of non-peer reviewed open literature was considered beyond the remit of Article 8(5) of Regulation (EC) No 1107/2009. The draft described an approach that was time and resource consuming. The draft did not provide a prescriptive list of information sources/databases to search. The draft did not define a method for identifying relevance criteria for inclusion of studies in the dossier and for ensuring the consistency of relevance criteria used by the applicants. The draft did not clearly explain how to assess the reliability of the studies included in the dossiers and use them in the risk assessment. 3. EFSA consideration of the most frequently raised issues Regarding the inclusion of non-peer reviewed literature, in the draft version of the EFSA Guidance scientific peer-reviewed open literature was given a broad definition in order to enable inclusion in the dossiers, upon justification, of scientific reports conducted to a consistently high standard although without employing the same processes of external review applied by scientific journals. This approach was in line with best evidence synthesis practices in human health research, where editorial peer review is not considered the sole guarantee of methodological quality and readers are encouraged to exercise critical appraisal skills when assessing the quality of published research. In light of the comments received, the final Supporting Publications 2011:125 5

6 Public Consultation on the draft on Submission of scientific peer-reviewed open literature under Regulation (EC) No 1107/2009 version of the now provides a definition of the peer-review process and clarifies that applicants will have a legal obligation to provide only documents falling under the category of scientific peer-reviewed literature. The EFSA working group acknowledged the increased workload that searching for peerreviewed open literature in a systematic way for dossier preparation may generate. However, the was produced in compliance with the requirements of Art. 8(5) of Regulation (EC) No 1107/2009 and proposes a method which is as practical as possible. The final version of the includes an example for a real active substance that has been marketed for a long time, to show the feasibility of the approach and illustrate the necessary resources in terms of time and personnel required for a worst case situation. Three additional examples of literature searches for substances more recently introduced to the market are also included in the ; they indicate that the proposed approach should be less onerous and more straightforward for the majority of active substances. Advice on identifying suitable sources of scientific peer-reviewed open literature can be sought from information specialists, web-based resource lists and library guides. Support may also be asked from Rapporteur Member States and EFSA. The final version of the now provides a framework of principles that can be used to develop relevance criteria for studies to be included in the dossier. Practical examples are also given. No universally accepted approach for assessing the reliability of the studies included in a dossier has yet been tested and agreed. However, the final version of the includes a discussion on the definition of reliability in this context, some general principles that may be considered in the assessment, and a list of references to possible schemes that can be applied to classify the studies according to their likely reliability for use in risk assessment. Links to the guidance documents normally used in the European assessment of plant protection active substances in the regulatory framework of directive 91/414/EEC are also provided. Supporting Publications 2011:125 6

7 Public Consultation on the draft on Submission of scientific peer-reviewed open literature under Regulation (EC) No 1107/2009 APPENDIX 1 PUBLIC CONSULTATION ANNOUNCEMENT The text below is from the EFSA website of the public consultation: on Submission of scientific peer-reviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/ Extended deadline: 15 October 2010 at noon Update: Kindly note that the deadline for this call has been extended to 15th of October 2010 at noon This draft provides instructions on how to identify and select scientific peerreviewed open literature as required by Article 8(5) of Regulation (EC) No 1107/2009[1] on the placing of plant protection products on the market and how to report it in a dossier. For the development of this draft, the Assessment Methodology Unit (AMU) of EFSA, in collaboration with the Unit on Pesticide Risk Assessment Peer Review (PRAPeR), has established a working group of EFSA external members and scientific officers. An advanced draft of the Guidance was submitted to the EFSA Panel on Plant Protection Products and their Residues and the Pesticide Steering Committee and their feedback was considered by the working group members to produce the currently available version of the Guidance. The draft Guidance would benefit from a broad range of comments, which may support its clarity, completeness and soundness. This public consultation therefore aims to gather the widest range of views to finalise the Guidance and provide the most up-to-date and comprehensive scientific advice to the users of the Guidance. Interested parties are invited to submit written comments by 6 September 2010 at A submission will not be considered if it: * is submitted after the deadline set out in the call; * is presented in any form other than what is provided in the instructions and template; * does not relate to the contents of the document; * contains information on individual cases; * contains complaints against institutions, personal accusations, irrelevant or offensive statements or material; * is related to policy or risk management aspects, which is out of the scope of EFSA's activity. EFSA will assess all relevant comments from interested parties which are submitted in line with the above criteria. The comments will be evaluated by the experts of the working group and taken into consideration where these will enhance the scientific quality or understanding of the Guidance. EFSA will publish the relevant comments received, as well as a short report on the outcome of the consultation. Published: 23 July [1] OJ L309, , p. 1. Supporting Publications 2011:125 7

8 APPENDIX 2 FULL LIST OF COMMENTS AND RELATED EFSA REPLIES This compilation contains the comments submitted to EFSA via the public consultation held from 23 July to 15 October Comments submitted by individuals in a personal capacity are presented anonymously. Comments submitted formally on behalf of an organisation appear with the name of the organisation. In cases where comments address similar issues EFSA has provided a standard reply; the standard replies are repeated throughout the document in an effort to save stakeholders time having to cross-refer to a single list of comments. European Food Safety Authority,

9 1. Federal Environment Agency (UBA) DEU 2. Finnish Environment Institute FIN Abstract Abstract Comments of UBA on the draft guidance document of EFSA on submission of scientific peer-reviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/2009. The consideration of scientific peer-reviewed open literature is highly important in evaluation of dossiers for the approval of pesticide active substances under Regulation (EC) No 1107/2009. There remain some gaps in the draft EFSA GD related to the analyses and implementation of outcomes from selected studies into the risk assessment. EFSA: The has been updated taking this comment into consideration. The now includes a on reliability that incorporates a discussion of its definition, some general principles, references to classification schemes and links to guidance in the regulatory assessment framework for plant protection active substances. It is clear that the whole process identification and selection of relevant studies and evaluation of data and its use for regulatory purposes will be time consuming. This is to be aware of and proper measures should be taken in order to meet new requirements on this issue of scientific peer-review open literature for the approval of pesticide active substances. EFSA: EFSA acknowledges the increased workload that literature searches may generate in the dossier preparation process. However this was produced to comply with the requirements of Art. 8(5) of Regulation (EC) No 1107/2009. Appendix B of the provides examples of single concept searches for peer-reviewed open scientific literature for three active substances which have little literature. Appendix C of the provides a description of the method and the resources required to perform the rapid assessment of available summary records (the first step of the study selection process) for an active substance for which an extensive amount of literature has been published. The examples illustrate the feasibility of the approach for a worst case scenario and more typical scenarios. Furthermore, information collected from the peer reviewed scientific literature may help to finalise the risk assessment, thereby saving resources for applicants and authorities risk assessors. The article 8 (5) of the regulation 1107/2009 requires that scientific peer-reviewed open literature, as determined by the Authority, on the active substance and its relevant metabolites dealing with side-effects on health, the environment and nontarget species and published within the last 10 years before the date of submission of the dossier shall be added by the applicant to the dossier. We welcome that a guidance document on this requirement is under development. As wished, we would like to make a few comments on the application of the article 8(5) and the draft document. We see the importance of the scientific literature search, since new important data might come up by this search. It is not clearly written out in the guidance document, when a literature search should be performed and therefore it would be very useful to advise risk assessors, whether it is a decision of the applicant on which data requirement points a literature search is performed Supporting Publications 2011:125 9

10 or should it always been performed as widest, by the name of the active substance as such, which might lead to huge data basis. EFSA: This has been clarified in the. Scientific peer-reviewed open literature should be searched and selected for all data requirements dealing with side-effects on health, the environment and non-target species as listed in the EFSA Guidance. We would like to pay attention to the huge workload that the article 8(5) produces especially for companies and for Member State authorities if no clear guidance is given when the scientific literature search is seen necessary. If a wide literature search concerning all data requirements is performed for all active substances, it will cause a workload that might be impossible to manage especially in cases with old active substances. Even the example with Chlorpyrifos (old substance) presented in the EFSA draft guidance, the scientific literature search is restricted to only a few alternative names for plant protection products containing Chlorpyrifos and for the risk assessment part of toxicology to keep, as written in the report, the example manageable. The literature search, produced with narrow search conditions, retrieved at least 1780 records. Therefore, even seeing the literature search an important way of obtaining also data on possible effects not covered by studies produced by applicant, we are also of the opinion that some kind of regulations should be decided in which cases scientific literature searches are performed; otherwise we are worried that the implementation of the article 8(5) might not be possible to realize. EFSA: EFSA acknowledges the increased workload that literature searches may generate in the dossier preparation process. However this was produced to comply with the requirements of Art. 8(5) of Regulation (EC) No 1107/2009. Appendix B of the provides examples of single concept searches for peer-reviewed open scientific literature for three active substances which have little literature. Appendix C of the provides a description of the method and the resources required to perform the rapid assessment of available summary records (the first step of the study selection process) for an active substance for which an extensive amount of literature has been published. The examples illustrate the feasibility of the approach for a worst case scenario and more typical scenarios. Furthermore, information collected from the peer reviewed scientific literature may help to finalize the risk assessment, thereby saving resources for applicants and authorities risk assessors. In conclusion, we consider that the data packages that will be provided according to 1107/2009 by the applicants are quite extensive, and therefore we suggest that scientific public data included in the dossiers could mainly deal on the effects that are not covered by the studies submitted by the applicants. Bearing in mind the possible huge amount of retrieved records, we are of the opinion that it could be useful to discuss once again when to use scientific data before the guidance is published. We also think that the guidance should be developed, when more experience is gathered within the practical work. Supporting Publications 2011:125 10

11 3. CBC Europe Ltd Abstract EFSA: The proposal to submit only literature on side effects not covered by the studies submitted by the applicants could not be taken into account as this would restrict the scope of the Art 8(5) in the Regulation (EC) No 1107/2009. The will be reviewed and may be revised once experience is gained in applying it. In Article 8(5) it is clearly written scientific peer-reviewed open literature, so inclusion of non-peer-reviewed scientific literature is not acceptable 4. European Crop Protection Agency (ECPA) BEL EFSA: The has been updated taking this comment into consideration. Abstract ECPA is the trade association for European manufacturers of crop protection protects. This response is made on behalf of the 18 ECPA member companies. ECPA welcomes the opportunity to comment on the draft guidance and the openness of EFSA in ensuring stakeholder comments are considered. We welcome clear and practicable regulatory guidance that can be applied consistently by applicants, Members States and EFSA. We believe the guidance is generally well written and clear. We do however, have several fundamental concerns with the document as drafted. Our general comments are included below and our detailed comments are included in each section: -ECPA is concerned that the guidance does not limit itself to clarifying the requirements of Article 8(5) of Regulation 1107/2009, but goes beyond the scope of this and introduces significant additional data requirements. The guidance states a wider definition is given to enable inclusion of non peer-reviewed scientific literature, where justified. However, the role of guidance should be to ensure a common understanding of the legislation in place. Introducing new requirements that are not in line with the legislation is not acceptable and this aspect needs to be amended. EFSA: The has been updated taking this comment into consideration. -While we accept the need to provide information on scientific peer-reviewed open literature, it is unreasonable to expect applicants to review all data sources on an active substance, its metabolites and plant protection products. ECPA is concerned about the significant additional workload the guidance will entail, particularly with the large volume of information that will need to be collected, evaluated, translated and submitted. This burden lies mainly with applicants but also with Member States and EFSA. EFSA: EFSA acknowledges the increased workload that literature searches may generate in the dossier preparation process. However this was produced to comply with the requirements of Art. 8(5) of Regulation (EC) No 1107/2009. Appendix B of the provides examples of single concept searches for peer-reviewed open scientific literature for three active substances which have little literature. Appendix C of the provides a description of the method and the resources required to perform the rapid Supporting Publications 2011:125 11

12 assessment of available summary records (the first step of the study selection process) for an active substance for which an extensive amount of literature has been published. The examples illustrate the feasibility of the approach for a worst case scenario and more typical scenarios. Furthermore, information collected from the peer reviewed scientific literature may help to finalize the risk assessment, thereby saving resources for applicants and authorities risk assessors. -ECPA questions whether the guidance as written will add significant value to the existing regulatory process, which already provides for submission of scientific literature. We are not aware of any cases where submissions have systematically missed relevant publications which would have impacted regulatory decisions. We support the principle of evaluating available scientific literature for relevance, but believe this should be focussed on information that will improve the risk assessment. EFSA: The requirement for including scientific peer-reviewed open literature is set by the Regulation. The provides a method for searching and selecting the scientific peer-reviewed open literature based on principles of methodological rigour, transparency and reproducibility and is of additional value to the existing regulatory process. -To keep the workload at a manageable level while still ensuring relevant literature is identified, we believe the search should be focussed on established databases and to bibliographic records provided in English. The guidance should further assist by specifying examples of acceptable databases, search platforms or journals. EFSA: Advice on identifying suitable sources of scientific peer-reviewed open literature can be sought from information specialists, web-based resource lists and library guides. Support may also be asked from Rapporteur Member States and EFSA. With regard to the language issue, the has been updated by specifying that the search strategies need to be in English only. Once assessed as relevant, full-text documents should preferably be provided in English; however, official EU languages would be accepted. Relevant full-text documents in non-eu languages should be translated to English. -Applicants should be required to provide only a reference list of available relevant literature (and not copies of all individual literature itself) along with a summary or evaluation. Based on this list if Member States or EFSA wish to see copies of specific literature, this can be provided by applicants. EFSA: The has been amended. Only copies of full-text documents not excluded after detailed relevance assessment need to be provided in the dossier. -Studies included in dossiers must be conducted according to GLP and OECD guidelines that set criteria for the study. Apart from rare exceptions, studies reported in the open literature are not performed according to the same GLP standards nor Supporting Publications 2011:125 12

13 5. JSC GBR Abstract according to such guidelines. It is of high concern that these studies are required and could be given the same weight under the guidance. EFSA: The requirement for the provision of studies available in the open literature is set by Article 8(5) of Regulation 1107/2009. All relevant studies shall be included in the dossier. The implies that relevant studies that provide data for establishing or refining risk assessment parameters are considered for reliability. They will also be assessed by the Rapporteur Member States and EFSA. This will guarantee that only relevant and reliable studies are used in the RA. -The guidance focuses on providing lists of referenced information and little detail on how to recognise what is of true value in improving the risk assessment. Much of the detail of how searches will be performed (e.g. the study protocol) is also left to the discretion of applicants, which does not foster consistency. The guidance should focus more on providing useful advice on the type of scientific literature to be included and how to assess the quality and relevance of this and on developing consistent approaches. EFSA: The has been updated taking this comment into consideration. The provides instructions on how to develop a search strategy and perform the search process; and a framework of general principles to assess relevance, supported with a practical example. Furthermore, the now includes a on reliability that incorporates a discussion of its definition, some general principles, references to classification schemes and links to guidance in the regulatory assessment framework for plant protection active substances. As a general comment we consider the document to be unnecessarily long and repetitive. We suggest bringing forward the examples from the Appendix into the main text with the aim of removing repetition and shortening the document. EFSA: The has been checked for repetitiveness. The examples have been further developed and left in the Appendices as it was considered that moving them would not improve clarity. Lines The procedure for evaluating and selecting the publications for inclusion in the submission is neither pragmatic nor practical. The effort required to carry out and present the results of a literature search, as described in the draft guidance, is disproportionate to the benefit, for industry, Member states and EFSA. Whilst there will have been little published research on new chemicals, for older chemicals, there will be thousands of hits in a literature search and the process of evaluating them will be very onerous. The chlorpyrifos example presented in Appendix A clearly demonstrates how difficult the process will be, especially if multiple sources of scientific literature are used. In our view inclusion of literature data should be far more targeted in the manner described at EFSA: EFSA acknowledges the increased workload that literature searches may generate in the dossier preparation process. Supporting Publications 2011:125 13

14 6. Chemicals Regulation Directorate GBR However this was produced to comply with the requirements of Art. 8(5) of Regulation (EC) No 1107/2009. Appendix B of the provides examples of single concept searches for peer-reviewed open scientific literature for three active substances which have little literature. Appendix C of the provides a description of the method and the resources required to perform the rapid assessment of available summary records (the first step of the study selection process) for an active substance for which an extensive amount of literature has been published. The examples illustrate the feasibility of the approach for a worst case scenario and more typical scenarios. Furthermore, information collected from the peer reviewed scientific literature may help to finalize the risk assessment, thereby saving resources for applicants and authorities risk assessors. CRD comments. General comment: applicable to several sections of the document including the abstract. We welcome the development of a guidance document for Member States, applicants and EFSA on the implementation of Article 8 (5). However we consider there is a fundamental flaw in the current draft. The document aims to provide guidance with respect to Article 8 (5) of Regulation 1107/2010. Article 8 (5) is unambiguous in its scope. The Article establishes a requirement in relation to active substance approval for Scientific peer-reviewed open literature, as determined by the Authority, on the active substance and its relevant metabolites dealing with side-effects on health, the environment and non-target species and published within the last 10 years before the date of submission of the dossier shall be added by the applicant to the dossier. However the authors of the draft guidance apply a wider definition which broadens the scope to include non-peer reviewed and grey literature as well as the inclusion of literature outside the required 10 year period. There is no legal basis for this extension of scope. We cannot support the inclusion of requirements and obligations for which there is no legal provision and which, if retained, would be likely to have an adverse impact on the timely delivery of the scientific risk assessments required under Regulation 1107/2010. We would therefore propose that the document is redrafted to ensure compliance with the terms of reference which are the implementation of Article 8 (5). There is other legislative provision relating to the submission of studies/information, outside the provisions of Article 8(5), that may be used by any stakeholder to ensure potentially adverse effects are considered in the regulatory process. EFSA: With regard to the peer review issue the has been updated. Scientific peer-reviewed open literature may also be included from more than ten years prior to dossier submission, provided that the literature is identified and selected in compliance with this and that clear justification is provided. In addition, and linked to the above extension of scope, we are concerned that the overall effect of the guidance, as currently drafted, is to place a high resource burden on both applicants and Member States. This is vividly illustrated by the example, Supporting Publications 2011:125 14

15 7. Ministère de l'alimentation, Abstract given in Appendix A, where limiting the search results in 1780 records for the active substance chlorpyrifos. Diversion of finite resources on a significant scale is a cause of concern as it may well have a detrimental effect on the overall quality of the regulatory submission, in particular, the quality of the assessments provided of the guideline compliant regulatory studies. Assessment of extensive literature submissions may also have consequential effects on the ability of Member States to meet the timelines laid out in the legislation. We would favour a more detailed specification in relation to the criteria for determining relevance in relation to the data requirements and identification of a recommended minimum set of database sources. Reduction of the potentially burdensome reporting requirements should be considered and alternatives, such as the provision of abstracts to the regulatory authority for further screening, considered. EFSA: EFSA acknowledges the increased workload that literature searches may generate in the dossier preparation process. However this was produced to comply with the requirements of Art. 8(5) of Regulation (EC) No 1107/2009. The provision of abstracts is not sufficient to ensure that the process is transparently reported, reproducible and may be adequately scrutinized by the reviewers. However, copies of the full-text documents considered irrelevant after either rapid or detailed assessment do not need to be provided. Appendix B of the provides examples of single concept searches for peer-reviewed open scientific literature for three active substances which have little literature. Appendix C of the provides a description of the method and the resources required to perform the rapid assessment of available summary records (the first step of the study selection process) for an active substance for which an extensive amount of literature has been published. The examples illustrate the feasibility of the approach for a worst case scenario and more typical scenarios. Furthermore, information collected from the peer reviewed scientific literature may help to finalize the risk assessment, thereby saving resources for applicants and authorities risk assessors. Advice on identifying suitable sources of scientific peer-reviewed open literature can be sought from information specialists, web-based resource lists and library guides. Support may also be asked from Rapporteur Member States and EFSA. At a practical level any finalised version of the guidance should be piloted by the Authority in conjunction with industry with the aim of short term revision in the light of experience. As the main impact will be in relation to existing substances the pilot could involve selected substances from the first batch of renewal substances (dossiers intended for submission in February 2012). This would enable some assessment of the benefits against the use of resources. EFSA: An update of the based on experience gained with its application to a number of substances may be considered by EFSA in agreement with relevant stakeholders. France thanks the EFSA for sharing its views on the review of literature data being relevant for the purpose of the evaluation of the effects and related risks of PPP in the frame of Directive 91/414/EEC and related regulation 1107/2009. The procedure Supporting Publications 2011:125 15

16 de l'agriculture et de la pêche FRA 8. BfR DEU Summary proposed is rigorous and of high quality. We however would like to point out that a proper application of such a procedure, understood as a quality check procedure for any literature review, might reveal to represent an extra important workload in the context of the current tight deadlines for the peer review. Indeed the insurance that the procedure has actually been followed implies that it is checked by the RMS using the review of the data submitted, which may need to check the good for between the list of papers reviewed and the procedure followed to select them. Such a procedure should implicitly be followed by the scientists in charge of the risk assessment of all boards, without that any further check is performed. In this respect, the literature review made in the course of the preparation of the papers themselves by editors is not submitted to any quality check of this type, which does not compromise the acceptance of this paper by the journal. EFSA: The provides instructions and recommendations on how to identify and select the scientific peerreviewed open literature in line with principles of methodological rigour and transparency. In particular the provides instructions on how to report in detail the review process, in such a way to simplify as much as possible the assessment by Member States and EFSA. EFSA acknowledges the increased workload that literature searches may generate in the dossier preparation process. However, this was produced to comply with the specific requirements of Art. 8(5) of Regulation (EC) No 1107/2009. Furthermore, information collected from the peer reviewed scientific literature may help to finalise the risk assessment, thereby saving resources for applicants and authorities risk assessors. With regards to the validity of the data as derived of the papers themselves, we could simply suggest, in order to save time and to improves the readability of the documents to be reviewed by the Authority and Member states a similar presentation in DAR, AR and addenda as done for other standardized studies so that it may easily be checked whether the data of the paper allow to derive the appropriate endpoint or brings the information that is needed for the risk assessment EFSA: The proposes to present the results of the literature search and selection according to the OECD Guidelines for the preparation of dossiers (as recommended by SANCO). General: This guidance will clearly improve the quality of dossiers by including a broader selection of open scientific literature that is taken into consideration and is evaluated for relevance. Trust of the public in the scientific assessment may become higher because it can be expected that much more references to studies will be incorporated that are not performed by chemical industry. However, notifiers will be responsible for search for and selection of studies from the public domain. In which way this process will be scrutinized by the authorities? In particular, there may be different views if a certain study from the public literature should be included in the dossier or not. Supporting Publications 2011:125 16

17 9. BfR DEU 10. CBC Europe Ltd Summary Summary EFSA: The gives instructions on how to report the search process and the study selection process in a transparent and standardised way, in order to allow the authorities to assess them. Criteria for study relevance and their applications would need to be assessed during the dossier peer review process. In addition, the amended requires all studies included in the dossier after the rapid assessment for relevance (i.e. after the first step of the study selection process) to be listed. This should enable risk assessors to scrutinise the selection done by the applicants. General: It may be beyond the scope of the document but it was noted that no guidance is given to what extent published data might be appropriate to replace (GLP compliant and Guideline-conform) studies that are usually produced and submitted by the notifiers. However, this is a question of practical importance, less with regard to chemical pesticides but in particular with respect to plant extracts, micro-organisms, anorganic substances, their salts and acids a.s.o. EFSA: The has been updated taking this comment into consideration. It includes a on reliability that incorporates a discussion of its definition, some general principles, references to classification schemes and links to guidance in the regulatory assessment framework for plant protection active substances. There is a lack of specific guidance on how to come from the 1780 (the chlorpyrifos example for human toxicity mentioned in the guideline) down to around maybe 5 to 10 open scientific peer-reviewed papers, which would be a manageable level for the applicant and the authorities doing the evaluation. (The applicants for chlorpyrifos actually submitted 5 scientific peer reviewed papers concerning human toxicity, none of them mentioned in the DAR by the RMS, SANCO/3059/99 - rev. 1.5). EFSA: The has been updated to provide additional examples where searches yielded far fewer studies (Appendix B) to illustrate that in most cases the search and the document assessment is far less onerous than the Chlorpyrifos example. However, the number of full-text documents which may be relevant and reliable cannot always be determined in advance (e.g., as proposed, 5-10 studies), as it will depend on the volume of peer-reviewed scientific literature which has been published for a specific substance. Appendix C of the provides a description of the method and the resources required to perform the rapid assessment of available summary records (the first step of the study selection process) for the topic side effects of Chlorpyrifos in human health. The examples illustrate the feasibility of the approach for a worst case scenario and more typical scenarios. Generally the guideline is off the target, because it gives guidance on how to find literature, but no guidance on what really matters; finding (assessing, deciding) the very few scientific peer-reviewed open literature papers, which could have an impact on the end points setting (appendix II of the final review report) and/or on the final risk assessment. If the Regulation 1107/2009 intends to speed up the procedure and reduce the workload for applicants and competent authorities, this guideline Supporting Publications 2011:125 17

18 11. European Crop Protection Agency (ECPA) BEL Summary certainly does not EFSA: The provides instructions and recommendations on how to identify and select the scientific peerreviewed open literature in line with principles of methodological rigour and transparency and in compliance with the requirements of Art. 8(5) of Regulation (EC) No 1107/2009. The has been updated taking this comment into consideration. The now includes a on reliability that incorporates a discussion of its definition, some general principles, references to classification schemes and links to guidance in the regulatory assessment framework for plant protection active substances. Page 2 mentions the wording of Article 8(5) of Regulation 1107/2009 which: requires that applicants submitting dossiers for the approval of active substances of plant protection products under Regulation (EC) No 1107/2009 shall provide Scientific peer-reviewed open literature, [ ], on the active substance and its relevant metabolites dealing with side-effects on health, the environment and non-target species and published within the last ten years before the date of submission of the dossier as determined by the European Food Safety Authority. As mentioned above, ECPA would highlight that Article 8(5) refers to scientific peer-review open literature and that the role of guidance should be to assist in clarifying the legislation in place. There is no legal basis to extend the mandate beyond what is required in Article 8(5) and the guidance should not compulsorily require the inclusion of all non-peer-reviewed literature. This element of the guidance therefore needs to be amended to ensure the scope remains on the identification and selection of the scientific peer-reviewed open literature. EFSA: The has been updated taking this comment into consideration. While we stress that the definition of Article 8(5) should not be ignored in the guidance, it should also be highlighted that during the EU review of active substances, the implementing legislation for the renewal of active substances approvals (AIR) does provide a clear opportunity for third parties to submit information to the rapporteur Member States in particular with regard to the potentially dangerous effects of the active substance or its residues on human and animal health and on the environment. ECPA supports this procedure and believes that this is the correct way forward of ensuring that all stakeholders have the opportunity to provide any relevant data for the review process, including the non-peer reviewed studies (grey literature) mentioned in the draft guidance document. EFSA: This comment refers to different legislation and is not relevant to scope of this. Page 2 states that: This Guidance was developed by a working group that considered in detail how to integrate best practices in evidence synthesis with the structure of existing Guidance documents to avoid unnecessarily increasing the effort needed to prepare and appraise dossiers. Unfortunately however, this is exactly what the guidance will do if the intention is to find and assess all publications. As commented above ECPA has serious concerns regarding the significant additional workload that the Supporting Publications 2011:125 18

19 guidance will entail for applicants (and their consultants) but also for Member States and EFSA who will be responsible for evaluating the large amount of additional information. We further question whether resources will truly be available within regulatory authorities to assess this and within the new timeframes specified in Regulation 1107/2009. In order to keep the workload manageable, it would be helpful, if the guidance document would specify the basic purpose of the literature review and further define the term relevant. The goal should not be to give a complete overview of all literature addressing any of the data requirements, but only include those peer-reviewed studies, which could potentially impact endpoints or risk assessments. We also believe the search should be focussed on using internationally recognised scientific databases such as those hosted by servers such as STN and DIMDI and to bibliographic records provided in English. This search should ensure almost all relevant literature is identified, while maintaining the workload burden at a reasonable and proportionate level. A review in such bibliographic and/or factual databases should then be assumed to fulfil the requirements of Article 8(5). The guidance could further assist by specifying a list of possible acceptable database providers, search platforms or journals. 12. JSC GBR Background provided EFSA as by EFSA: EFSA acknowledges the increased workload that literature searches may generate in the dossier preparation process. However this was produced to comply with the requirements of Art. 8(5) of Regulation (EC) No 1107/2009. Appendix B of the provides examples of single concept searches for peer-reviewed open scientific literature for three active substances which have little literature. Appendix C of the provides a description of the method and the resources required to perform the rapid assessment of available summary records (the first step of the study selection process) for an active substance for which an extensive amount of literature has been published. The examples illustrate the feasibility of the approach for a worst case scenario and more typical scenarios. Furthermore, information collected from the peer reviewed scientific literature may help to finalize the risk assessment, thereby saving resources for applicants and authorities risk assessors. The now clarifies that only relevant studies that provide data for establishing or refining risk assessment parameters should be summarised in detail and considered for reliability. Advice on identifying suitable sources of scientific peer-reviewed open literature can be sought from information specialists, web-based resource lists and library guides. Support may also be asked from Rapporteur Member States and EFSA. With regard to the language issue, the has been updated by specifying that the search strategies need to be in English only. Once assessed as relevant, full-text documents should preferably be provided in English; however, official EU languages would be accepted. Relevant full-text documents in non-eu languages should be translated to English. Lines There is no reasoned justification for the arbitrary cut-off for literature searches of 10 years. EFSA: The ten-year time is specified by Article 8(5) of Regulation (EC) No 1107/2009. Scientific peer-reviewed open literature may also be included from more than ten years prior to dossier submission, provided that the literature is identified and selected in compliance with this and that clear justification is provided. Supporting Publications 2011:125 19