Method Validation Revisited: Its Role in Traceability of Results

1. Method Validation Revisited: Its Role in Traceability of Results Wolfhard Wegscheider Institute for General and Analytical Chemistry University of Leoben, AUSTRIA wegschei@unileoben.ac.at

2. precision bias other effects Standard view of the relation between uncertainty and validation Measurement uncertainty from SLR Ellison 1999

3. Traditional roles of method validation • Establish performance characteristics • Linearity • Limits of detection/determination • Precision: repeatability, intermediate reproducibility • Effect of concomitants • Present data for approval of method • Produce control limits for everyday operation

4. limit results What should be the role of validation ? As analytical chemistry is about making decisions • validation should support the decision making process

5. Traditional role of traceability • Provide a firm and identical base of units worldwide • Supply this base in a manner stable in time • Underpin the hierarchy of measurements/procedures/laboratories • .....

6. Validation starts out from the customer´s needs Report results Report to customer Requirements of customer Convert to uncertainty Do analyses Accept/reject contract Apportion to the different steps Express as figures of merit Estimate factual uncertainty Specify validation plan Compute figures of merit Validate

7. Two key components to traceability: - standards - uncertainty combined uncertainty:

8. Uncertainty of a standard: • Identity • Purity • Preparation

9. NO uncertainty from standard With uncertainty from standard and dilution Influence of uncertainty of standards in calibration M. Rösslein, EMPA2001

10. Two (extreme) ways to define the measurand / analyte A) Careful and complete description of circumstances: • (exactly) what species • What (kind of) samples/concomitants • Which environmental conditions (p, T) B) Measure as specified and give the analyte a name

11. A general model of measurement and validation in chemistry huge and unknown for N results: somewhat smaller, but unknown

12. A general model of measurement and validation in chemistry After validation: small and accessible from precision data identified effects on result

13. Two extreme ways to define the measurand /analyte: MODEL 1 A) Measure as specified and give the analyte a name: Accessible through interlab comparisons The „new“ analyte

14. Two extreme ways to define the measurand /analyte: MODEL 2 B) Careful and complete description of circumstances: Very small part of uncertainty The „old“ analyte well defined

15. The Measurement of pHIUPAC Working Party on pH • Notational definition: • Operational definition:

16. Operational Definition of pH • Debye-Hückel formalism with Bates-Guggenheim convention • (only) 5 primary buffers • 3 < pH < 10 • I < 0.1 mol/l • Aqueous solution

17. Uncertainty of standard methods:experience in practice avoid + udef + ucorr real + udef uncertainty (a.u.) bottom-up a b c

18. Redesigning validation studies: what has been missing so far ? • Establish the quality of the standards • Complete coverage of scope OR clear redefinition of the analyte • Anchored in the requirements of the customer

19. Traceability of results and reference values is a central issue in modern laboratory operation. It is not an end in itself, but serves the purpose of achieving a reliable result. • Traceability of results can only be claimed if results are accompanied by an uncertainty statement based on traceability of all references, chemical and physical, as well as on procedural contributions to uncertainty. • A result must be "fit for purpose", thus estimation of measurement uncertainty from uncertainties of references and procedures is added value for laboratories and simple when guidelines are followed.