Evaluation & Reporting of Data: How to provide a (robust) study summary Webinar on Information requirements 30 November 2009 http://echa.europa.eu Evaluation of all available information • Step 1: Evaluation of the data quality – Relevance – Adequacy – Reliability • Step 2: Selection of key study(ies) for each endpoint • Step 3: Drafting (robust) study summaries http://echa.europa.eu Evaluate the data Step 1: Evaluate 1.1 Relevance 1.2 Adequacy 1.3 Reliability Klimisch scoring 2. Adequate studies available? NO YES YES One adequate study One key study More than one adequate study One clear key study and supporting study(ies) Less reliable studies Different/ conflicting adequate information WoE 3. RSS 3. RSS for key study 3. SS for supporting study(ies) Step 2: Select 3. RSS for all studies used as part of the Weight of Evidence (WoE) WoE Step 3: Draft http://echa.europa.eu Step 1: Evaluation of data quality Step 1: Evaluation of data quality a. Relevance • Data and tests are appropriate for a particular hazard identification or risk characterisation • Especially following questions should be considered: • • • • • • Has the right/appropriate/suitable test been selected ? Is the test substance the same as the registered substance? Has an appropriate organism/species been tested? Is the route of exposure relevant? Has an appropriate doses/concentrations been tested? Were the critical test parameters influencing the endpoint considered adequately? http://echa.europa.eu Step 1: Evaluation of data quality b. Adequacy • Information is sufficient for the purpose of C&L and/or risk assessment • Data should allow clear decision-making: • the substance meets the criteria for classification and labelling • the substance is a potential PBT/vPvB • appropriate DNEL/PNEC values can be derived for risk assessment purposes • data is sufficient for specific requirements http://echa.europa.eu Step 1: Evaluation of data quality c. Reliability • Quality of the study, method, reporting of results and conclusions • Reliability can be assessed using Klimisch scoring system • • • • 1 = reliable without restrictions 2 = reliable with restriction 3 = not reliable 4 = not assignable For reliability assessment see Guidance R.4.2. http://echa.europa.eu Step 1: Evaluation of data quality c. Reliability • Klimisch et al. 1997 – 1 = reliable without restrictions: • “studies or data [...] generated according to generally valid and/or internationally accepted testing guidelines (preferably performed according to GLP) or in which the test parameters documented are based on a specific (national) testing guideline [...] or in which all parameters described are closely related/comparable to a guideline method.” For reliability assessment see Guidance R.4.2. http://echa.europa.eu Step 1: Evaluation of data quality c. Reliability • Klimisch et al. 1997 – 4 = not assignable: • “studies or data [...] which do not give sufficient experimental details and which are only listed in short abstracts or secondary literature (books, reviews, etc.).” For reliability assessment see Guidance R.4.2. http://echa.europa.eu Evaluate the data Step 1: Evaluate 1.1 Relevance 1.2 Adequacy 1.3 Reliability Klimisch scoring 2. Adequate studies available? NO YES YES One adequate study One key study More than one adequate study One clear key study and supporting study(ies) Less reliable studies Different/ conflicting adequate information WoE 3. RSS 3. RSS for key study 3. SS for supporting study(ies) Step 2: Select 3. RSS for all studies used as part of the Weight of Evidence (WoE) WoE Step 3: Draft http://echa.europa.eu Step 2: Selection of key study http://echa.europa.eu Step 2: Selection of key study • Key study = study of greatest relevance – the most suitable to describe an endpoint – the basis for the risk assessment • How to select key study(ies) – Determine a key study for each endpoint • based on the relevance, adequacy & reliability of the study(ies) • usually the study which gives highest concern • reliability indicator for a key study (Klimisch score) is 1-2 http://echa.europa.eu Step 2: Selection of key study Evaluate the data Step 1: Evaluate 1.1 Relevance 1.2 Adequacy 1.3 Reliability Klimisch scoring 2. Adequate studies available? NO YES YES One adequate study One key study More than one adequate study One clear key study and supporting study(ies) Less reliable studies Different/ conflicting adequate information WoE 3. RSS 3. RSS for key study 3. SS for supporting study(ies) Step 2: Select 3. RSS for all studies used as part of the Weight of Evidence (WoE) WoE Step 3: Draft http://echa.europa.eu Step 3: Drafting a Robust Study Summary WoE 3. RSS 3. RSS for key study 3. SS for supporting study(ies) 3. RSS for all studies used as part of the Weight of Evidence (WoE) http://echa.europa.eu WoE Step 3: Drafting a Robust Study Summary (1) • “A detailed summary of the objectives, methods, results and conclusions of a full study report that provides sufficient information to make an independent assessment of the study, while minimising the need to consult the full study report” [see: Article 3 (28)]. • Level of detail needed? http://echa.europa.eu Step 3: Drafting a Robust Study Summary (2) • Robust Study Summary (RSS) contains as many details as necessary: – To describe the test protocol and justify the validity of the result – To assess the reliability and completeness of the study without having to go back to the full study report – To assess whether the correct key study(ies) has/have been chosen for an endpoint • IUCLID = Detail level 2 – Basic fields + Additional information • IUCLID display type = "all fields” http://echa.europa.eu Step 3: Drafting a Robust Study Summary (3) • When is RSS required? – if required under Annex I in the technical dossier (Article 10 (a)(vii)) • This means: – when CSR is required (substances at or above 10 tpa) – for key studies http://echa.europa.eu Step 3: Drafting a Robust Study Summary (4) • RSS is recommended: – for all key studies • also for substances less than 10 tpa • also for physico-chemistry end-points – for all studies that are used as part of the Weight of Evidence (WoE) – for non-key studies demonstrating a higher concern than a key study – when the study gives ambiguous results – when the study is performed according to non-standard protocols See: Guidance on registration, 8.2.2.6.2 Step 3: Drafting a Robust Study Summary (5) • When using old studies: – Physico-chemical, human health and environmental tests not performed according to test guideline and GLP – Historical human data • the information should be sufficient for Classification & Labelling and/or risk assessment • the information should be scientifically valid • adequate documentation must be provided http://echa.europa.eu Step 3: Drafting a Robust Study Summary (6) • What to provide for old studies: – Robust Study Summary to enable ECHA to evaluate this non-standard data • Need for justification – when used as a key study justification ALWAYS needed • Annex XI.1 – No justification is needed if the study is submitted as a supportive study More deviations from the standard testing guideline more information needed to enable a good evaluation!!! http://echa.europa.eu Step 3: Drafting a Robust Study Summary (7) • Use of studies as supporting information: • Valid study but reliability lower than that of key study • Used in WoE and/or as supportive studies • Registrant’s specific tasks • Report reasons why specific key study has been selected provide Study Summary for supportive studies • BUT when supportive study indicates higher concern than the selected key study provide Robust Study Summary for supportive studies http://echa.europa.eu Step 3: Drafting a Study Summary (1) • “A summary of the objectives, methods, results and conclusions of a full study report providing sufficient information to make an assessment of the relevance of the study” [see: Article 3 (29)]. • Level of detail needed? http://echa.europa.eu Step 3: Drafting a Study Summary (2) • Level of detail: – Less detailed than RSS – Information must be provided in sufficient detail to allow evaluation of the relevance of the study • IUCLID = Detail level 1 – Relevant for all study summaries • IUCLID display type "basic fields” – as defined in the OECD harmonised templates. – these fields should be completed for each study summary as far as possible. http://echa.europa.eu Step 3: Drafting a Study Summary (3) • When to provide: – for key studies submitted for registration of substances manufactured/imported at 1-10 t/a (REACH Annex VI and VII) • ECHA recommends to provide RSS – for supportive studies • Unless supportive study shows a higher concern than the key study http://echa.europa.eu Experience so far • Robust study summary quality show important differences in quality ! • Frequent errors: – validity, reliability, repeatability criteria missing • No independent evaluation possible – poor reporting of test results • Tabular or graphical form preferred – unclear or insufficient level of detail on test material – justifications for key study selection – missing final conclusions at end of endpoint study record http://echa.europa.eu Practical IUCLID tips • How to fill in a robust study summary in IUCLID 5 http://echa.europa.eu Practical IUCLID tips When drafting RSS - Use the detail level 'all fields' in IUCLID technical dossier Guidance on registration, 8.2.2.6.1 http://echa.europa.eu Drafting RSS in IUCLID http://echa.europa.eu Study StudyDesign Design Details Detailsononinoculum inoculum Parameter forfor biodegradation estimation Parameterfollowed followed biodegradation estimation Details methods Detailsononanalytical analytical methods Details design Detailsononstudy study design Practical IUCLID tips • How to fill in the study summary in IUCLID 5 http://echa.europa.eu Practical IUCLID tips When drafting Study Summary - Use the detail level ‘basic fields' in the IUCLID technical dossier Guidance on registration, 8.2.2.6.1 http://echa.europa.eu Drafting Study Summary in IUCLID http://echa.europa.eu StudyDesign Design Study Anyother otherinformation information materials methods tables Any onon materials andand methods incl. incl. tables Key messages and references GOOD DOCUMENTATION necessary for a reliable evaluation Key study Robust study summary References: • Guidance on registration • IUCLID 5 End User Manual • Manual on robust study summaries http://echa.europa.eu