Method Validation Revisited: Its Role in Traceability of Results

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Method Validation Revisited Its Role in
Traceability of Results

• Wolfhard Wegscheider
• Institute for General and Analytical Chemistry
  University of Leoben, AUSTRIA
• wegschei_at_unileoben.ac.at

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Standard view of the relation between uncertainty
and validation
Measurement uncertainty
from SLR Ellison 1999
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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

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What should be the role of validation ?

• As analytical chemistry is about making decisions
• validation should support the decision making
  process

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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
• .....

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Validation starts out from the customers needs
Requirements of customer
Report to customer
Report results
Convert to uncertainty
Do analyses
Apportion to the different steps
Accept/reject contract
Express as figures of merit
Estimate factual uncertainty
Specify validation plan
Compute figures of merit
Validate
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Two key components to traceability
- standards
- uncertainty
combined uncertainty
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Uncertainty of a standard

• Identity
• Purity
• Preparation

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Influence of uncertainty of standards in
calibration

• NO uncertainty from standard

• With uncertainty from standard and dilution

M. Rösslein, EMPA2001
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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

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A general model of measurement and validation in
chemistry
huge and unknown
for N results
somewhat smaller, but unknown
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A general model of measurement and validation in
chemistry
After validation
small and accessible from precision data
identified effects on result
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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
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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
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The Measurement of pHIUPAC Working Party on pH

• Notational definition
• Operational definition

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Operational Definition of pH

• Debye-Hückel formalism with Bates-Guggenheim
  convention
• (only) 5 primary buffers
• 3 lt pH lt 10
• I lt 0.1 mol/l
• Aqueous solution

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Uncertainty of standard methodsexperience in
practice
avoid udef ucorr
real udef
uncertainty (a.u.)
bottom-up
a b
c
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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

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• 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.