1. NORMAN-CMA Joint Meeting, Paris 21 Oct 2008 NORMAN support for validation of methods at the European level David Schwesig - IWW Water Centre, Germany - Contributors: Biosense, Cemagref, Ineris, ITM, IVM, NPL, RIVO, VUVH, CSIC, UBA, UK-EA

2. NORMAN – CMA Joint Meeting, Oct 2008 NORMAN Project objectives Creation of a network among European reference laboratories dealing with emerging pollutants The approach will foster: –co-operation and data transfer of environmental analysis between monitoring institutes, risk assessors and regulatory bodies –validation and harmonisation of monitoring tools –accelerate the availability of reliable & comparable data on emerging pollutants

3. NORMAN – CMA Joint Meeting, Oct 2008 A harmonised approach to validation has been developed within NORMAN by biological and chemical experts is not restricted to emerging pollutants has taken into account existing european and international standards and guidelines wherever possible –E.g. on sampling, terminology, statistics, organisation and evaluation of interlabs/PTs, performance criteria, uncertainty… is based on a three-level approach download: www.norman-network.net

4. NORMAN – CMA Joint Meeting, Oct 2008 Why 3 Levels of Validation? European-wide monitoring is usually not needed in the initial phase of an emerging issue/pollutant  First reports from research, based on internal validation (Level 1) A potential "emerging issue" may turn out to be either - no problem at all - or only of local importance  Method applicable by a few expert labs sufficient (Level 2) Large-scale monitoring needed at the European level  Method applicable by routine laboratories and suitable for standardisation (Level 3)

5. NORMAN – CMA Joint Meeting, Oct 2008 V1: Validation for Research Laboratories Starting point research method(s) available Existing method inappropriate for matrices, compartments or organisms of interest rudimentary internal validation (single lab only) End point: Method appropriate for matrix, compartment or organism of interest e.g. sufficient sensitivity & selectivity complete internal validation no external validation short record of method performance Selection, Adaptation, internal Validation

6. NORMAN – CMA Joint Meeting, Oct 2008 V2: Validation for Expert Laboratories Starting point: Appropriate (research) method for matrix, compartment or organism of interest (sufficient sensitivity & selectivity) complete internal validation short record of method performance missing external validation End point: Appropriate expert method with complete internal validation external validation: transferability proven due to poor or unknown robustness: applicable by expert laboratories only Method selection & external validation by „transferability study“

7. NORMAN – CMA Joint Meeting, Oct 2008 V3: Validation for Routine Laboratories Starting point: appropriate method with complete internal validation external validation incomplete due to poor or unknown robustness: applicable by expert laboratories only End point: fully validated method (internal & external) sufficient robustness to be applicable by routine laboratories high degree of unambiguous documentation (SOP) QA/QC procedures part of method (description) realistic potential for standardisation (CEN) External validation, linkage of QA/QC procedures to the method

8. NORMAN – CMA Joint Meeting, Oct 2008 Scope of the validation protocols Air Soil & Sediment Water Marine systems Biota Chemical methodsBiological methods ! Protocols applicable to a wide range of monitoring & biomonitoring methods (chemical & biological) and environmental matrices.

9. NORMAN – CMA Joint Meeting, Oct 2008 Development & implementation Improvement & Implementation of the Validation Protocols §§ „Lobbying“ at CEN level for implementation in standardisation (TC 230) Implementation at CMA? Development of protocols for method validation Case studies („Road-Test“ of the 3 validation protocols) Oestrogens in wastewaters (level V1) Non-steroidal anti-inflammatory drugs in waters (level V2) DecaBDE in dust (level V3)

10. NORMAN – CMA Joint Meeting, Oct 2008 Implementation - Standardisation Initiate the implementation of the protocols in the field of European Standardisation –A new work item for a technical guidance document will be proposed to CEN TC 230 (Water Analysis) –This procedure will soon be initiated by a proposal from the project co-ordinator to CEN If implementation at CEN is sucessful  ISO? Work under Mandate M424 from DG ENTR to CEN will make use of the NORMAN validation protocols where possible

11. NORMAN – CMA Joint Meeting, Oct 2008 Implementation - CMA Propose the incorporation of the protocols in guidelines for European monitoring activities –presented to CMA group (14 May 2008) –Reference to the validation protocols integrated in the Guidance Document on Surface Water Monitoring –…–…

12. NORMAN – CMA Joint Meeting, Oct 2008 Future use of the protocols Dissemination of the approach by placing a publication in an international (analytical) journal NORMAN will carry out method validation trials for emerging substances of interest These studies will follow the NORMAN validation protocols Interlaboratory studies for method validation on e.g., –pharmaceuticals & hormones –PFC in samples from sewage treatment –Pesticides and their metabolites –Organic phosphorous flame retardants –Siloxanes  For detailed information see Joint Programme of Activities for 2009 / 2010

13. NORMAN – CMA Joint Meeting, Oct 2008 Summary Harmonised protocols for method validation have been developed and tested Protocols will (hopefully) be implemented in the field of European standardisation, and widely accepted Norman network will work according to these protocols and foster the dissemination of the approach Step towards a common EU approach for method validation (comparable & reliable data)

14. NORMAN – CMA Joint Meeting, Oct 2008 Definition of Validation Method validation is the process of verifying that a method is fit for its intended purpose, i.e. to provide data suitable for use in solving a particular problem or answering a particular question. This process includes: –establishing the performance characteristics, advantages and limitations of a method and the identification of the influences which may change these characteristics, and if so to what extent, and –a comprehensive evaluation of the outcome of this process with respect to the fitness for purpose of the method.

15. NORMAN – CMA Joint Meeting, Oct 2008 Main Tasks of the 3 Levels Validation at level V1 (Research Labs): - complete internal validation (within 1 lab) - (extending the applicability to the matrix of interest) Validation at level V2 (Expert Labs): - test the principal transferability Validation at level V3 (Routine Labs): - comprehensive external validation by interlaboratory method validation study (involving routine laboratories)

16. NORMAN – CMA Joint Meeting, Oct 2008 Testing the Protocols VALIDATION 4 Improvement of protocols V1-V3 Implementation as guidelines on a European level CASE study 1 test protocol V1 CASE study 2 test protocol V2 CASE study 3 test protocol V3 VALIDATION 1 Research level VALIDATION 2 Expert level VALIDATION 3 Routine level Development of protocols Test phase of protocols Feedback, Improvement & Implementation §§

17. NORMAN – CMA Joint Meeting, Oct 2008 Feedback from Case studies Protocols are clear, unambiguous, useful Give a good introduction to the concept of validation and the different levels Could be effectively used to carry out the validation work Sometimes too much details are asked for Some overlap / redundancies between the different chapters

18. NORMAN – CMA Joint Meeting, Oct 2008 Improvement of the protocols Removal of redundancies and overlaps especially in the requirements on documentation of method and validation results Structure simplified Increase consistency in terminology & style throughout the 3 main parts Additions to glossary Improved version will be available before end of the project (November 2008)

19. NORMAN – CMA Joint Meeting, Oct 2008 Combination of the 3 protocols into 1 single document Structure & Key Elements of the Protocols Annex, References, Glossary Overarching chapters (Preface, Aims & Scope, Introduction, Concept) Method classification research (V1), expert (V2), routine (V3) level? Sampling guidance (biota, soil/sediment, water, air) Method selection (level-specific) V 1 Validation at research level V 2 Validation at expert level V3 Validation at routine level download for review: www.norman-network.net

20. NORMAN – CMA Joint Meeting, Oct 2008 Validation Procedure & Protocols Research method, incomplete internal validation, probably not applicable for organism, compartment or matrices of interest Method applicable by research labs (complete internal validation) Method applicable by expert labs (transferable to another lab with sufficient expertise) Method applicable by routine labs (comprehensive external validation) Validation Protocol V1 Validation Protocol V2 Validation Protocol V3 Method validation & maturity status

21. NORMAN – CMA Joint Meeting, Oct 2008 Guiding Principles Less specific & detailed procedures - More overarching validation principles applicable to all types of methods Integration of existing validation frameworks and guidelines as far as possible (e.g. OECD, Eurachem, ICCVAM, IUPAC...) Use terms, criteria & procedures with a high level of acceptance in the scientific community Adaptation to the 3-level approach and the specific needs of monitoring labs Create a validation framework with enough flexibility to be applicable for all relevant validation tasks related to monitoring & biomonitoring of EP