sief webinar: weight of evidence (woe) approach · 4. document your case in iuclid 5 contd. for...

http://echa.europa.eu

SIEF Webinar: Weight of Evidence (WoE) Approach


Contents

• WoE concept – when it can be used

• Steps to building a WoE case

• Experience with registration dossiers to date

• Case studies

• Conclusions


When to use WoE?


Weight of Evidence – the concept (1)

• In REACH the approach is provided as an option in Annex XI for meeting information requirements in Annexes VII-X

• Evidence-based approach, involving an assessment of the relative weights of different pieces of the available information – strengths versus weaknesses

• Requires expert judgement



• Weights will be influenced by e.g. the following factors:– quality of the data, – consistency of results/data, – nature and severity of effects, – relevance of the information for the given regulatory

endpoint.

• In all cases the relevance, reliability and adequacy for the purpose have to be considered



• WoE is case dependent and endpoint-specific• Use influenced by the relation between

– the amount of information needed– the importance of the decision to be taken by

Registrant– the likelihood of, and consequences for, the decision

being wrong


Legal basis (Annex XI 1.2)

…evidence from several independent sources … while the information from each single source alone is regarded insufficient…

…from the use of newly developed test methods … or from an international test method recognised by the Commission or the Agency as being equivalent…

Where sufficient WoE … is available:– further testing on vertebrate animals … shall be omitted,– further testing not involving vertebrate animals may be omitted.

In all cases adequate and reliable documentation shall be provided.


Why is WoE approach useful?

• It makes use of all available information

• Can use less reliable studies/information when included in a pool of information

• Used in developing Integrated Testing Strategies (ITS)

• May avoid the need for further testing


Steps to building WoE case1) Gather all information

� Literature search (e.g. scientific journals, handbooks, databases)

� Read across from similar substances

� Q(S)AR predictions

� Data from existing studies

� Newly developed test methods

� In vitro studies

� Epidemiological dataThe more the better!


Steps to building WoE case

2) Assess the data

� Are there 2 or more pieces of information?� Is the information relevant to the endpoint?� Is there adequate documentation of studies?� What is reliability/weight of each piece of data?� Is there consistency in results?� Is the combined weight substantial?


Steps to building WoE case

3) Draw a conclusion using expert judgement

� Integrate and compare different pieces of information

� Justify weight assigned to each piece of data

� Take into account:ReliabilityRelevanceAdequacy

� Expert Judgement is vital in the construction and appraisal of the WoE package


Steps to building a WoE

4. Document your case in IUCLID 5

� Adequate documentation for each piece of evidence = endpoint study record in IUCLID 5 for every piece of information

� Purpose Flag = Weight of Evidence

� Prepare Robust Study Summaries (RSS) for each study (also recommended for 1-10 tonne dossiers)

� Record reliability score


Steps to building a WoE

4. Document your case in IUCLID 5 contd.

� For studies with limited information, consider flagging as supporting study instead

� Reminder: minimum of one complete endpoint study record always required - key study, waiver with justification or weight of evidence

� Create an “Endpoint study summary ” to document conclusion of weight of evidence and justification for using this evidence instead of standard testing


Our Expectations

• Sufficient details provided for each piece of evidence to allow us to evaluate the overall evidence in an unbiased way

• The combined information allows for a conclusion to be drawn on the relevant endpoint

• The judgement made by the registrant is clearly documented and reported – in IUCLID 5 and CSR


Our Experience with registration dossiers to date

• Registrants are not always applying a WoE approach when it could be used

• WoE approach flagged but only 1 study reported, e.g. single QSARprediction for biodegradation. Several sources of evidence required for WoE, each with its own study record.

• Insufficient documentation and detail provided for each available data point

• Incorrect use of WoE flag for waiving a study on the grounds of lack of exposure. In this case, indicate in data waiving field the reason ‘exposure considerations’ and provide adequate justification.

• Good examples too, e.g. difficult-to test substance, 2 experimental results for short-term Daphnia toxicity and 1 QSAR prediction. Conclusion on endpoint made in endpoint summary.


Case Study (1)

WoE applied appropriately: Endpoint Study Record (a)


Case Study (1) contd.


Endpoint Study Record (b)


Endpoint Study Record (b) contd.


Endpoint Summary


Case Study 2: WoE inadequate


Case Study 2: WoE inadequate contd.


Conclusions

• WoE is useful approach to fulfil information requirements

• Makes use of all available information for an endpoint

• Requires expert judgement – every case different

• Clear, transparent documentation and argumentation essential


Links to relevant guidance

• REACH Guidance on information requirements and chemical safety assessment http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm?time=1259066690In particular:� Part B: Hazard Assessment� Chapter R.4: Evaluation of available information� Chapters R.7a, R.7b, R.7c: Endpoint specific guidance

• Weight of Evidence Manual – to be published

• Data Submission Manual 5 How to Complete a Technical Dossier for Registrations and PPORD Notifications (Release 2.1) – to be published

sief webinar: weight of evidence (woe) approach · 4. document your case in iuclid 5 contd. for...

Documents