Challenges in Method Validation – A Regulatory Laboratory Perspective

1. Challenges in Method
Validation – A Regulatory
Laboratory Perspective
Helen Cantwell
Rosemary Hayden

2. Contents
 What is Validation?
 Developing a validation procedure.
 Advantages of a harmonised approach.
 Challenges:
 Analytical Standards
 Multiple Matrices
 Measurement Uncertainty
 Proficiency Tests
 Ongoing verification
 Revalidation
 Eurachem Ireland

3. What is Validation?
 What is Validation?
Confirmation, through the provision of objective
evidence, that the requirements for a specific intended
use or application have been fulfilled.
ISO 9000
 Demonstrates that the analytical method is Fit
For Purpose.

4. Why Validate?
 Professional duty of the analytical chemist.
 Many decisions made based on the results of
analytical measurements.
 Health/safety
 Fines or imprisonment
 Valuing goods
 Provides laboratory knowledge e.g. critical steps in
the analytical procedure.

5. Developing a Validation Procedure
 Accreditation
 ISO 17025 General Requirements for the Competence of Testing
and Calibration Laboratories
 INAB Policy Documents
 Legislation
 2002/657/EC concerning the performance of analytical methods
and the interpretation of results
 SANTE/11945/2015 Guidance document on analytical quality
control and method validation procedures for pesticides residues
analysis in food and feed.
 The Water Framework Directive
 Publications
 The Fitness for Purpose of Analytical Methods. Eurachem, 2014

6. Advantages of a Harmonised Approach
 Allows analytical results to be compared with
each other.
 Allows decisions to be made based on collated
data e.g. limits set following food intake studies.
 Ensures that all appropriate performance
characteristics e.g. accuracy, precision,
robustness are examined.
 Facilitates efficient peer to peer discussion and
consultation.

7. Challenges – Analytical Standards
 Suppliers
 Accredited?
 Limited
 Demonstrate suitability
 Cert of Analysis
 How is purity determined?
 Demonstrate suitability before use?
 Demonstrate stability
 Solvent standards
 In matrix
 Labelled internal standards
 Expense
 Availability

8. Challenges – Multiple Matrices
 Different matrices/species
 Separate validation for each matrix/species
 Validate in one and show equivalency
 Divide into matrix types
 Different Maximum Residue Limit in
different matrices/species
 Full validation
 High time, cost, manpower

9. Challenges – Measurement Uncertainty
 Many different ways to calculate.
 Combining different individual components (modelling approach)
 Use of reproducibility data
 Use of PT data
 Eurachem guide: Quantifying Uncertainty in Analytical Measurement
 Robustness of MU value
 Initially calculated during validation
 Data gathered during ongoing use of method – more robust value
 Review of MU
 How often?

10. Challenges – Proficiency Tests
 INAB require successful participation in a
PT scheme.
 PT schemes not available for all analytes
in all matrices.
 Document alternate procedure.

11. Challenges – Ongoing Verification
 Validation – carried out before the method is in routine use.
 How to demonstrate that the method remains fit for purpose.
 Internal QC
 Control charts
 Proficiency tests
 Set acceptance criteria
 Validation vs routine use.
 Validation: known samples, limited sources/variables.
 Routine use: unknown samples, increased sources/variables.
 Demonstrate that data collected during validation remains valid.
 Introduce a programme of validation updates/verification.
 Set acceptance criteria.

12. Challenges – Revalidation
 When is revalidation necessary?
 Full validation or modified/abbreviated
validation?
 Increase the scope – add analytes, add matrices.
 New instrumentation – what if new instrument is more sensitive?
 Changes in legislation e.g. new/different MRLs.
 Major change in the method – what constitutes a major change?

13. Eurachem Ireland
 www.eurachem.org
 www.statelab.ie/eurachem.html
 Eurachem guide: The fitness for purpose
of Analytical Methods.
 Free to download
 Eurachem Ireland Mailing List

14. Eurachem Ireland
 Eurachem Method Validation Working Group
 Irish members: Helen Cantwell, Yvonne Bogan, John Clancy
 International workshop: Method Validation in Analytical
Science: Current Practices and Future Challenges
 May 9-10, 2016, Ghent
 Irish Workshop – Trainmic Metrology in Chemistry
 April 20th, 2016 in The State Laboratory, Celbridge.
 Use of reference material, internal QC and interlaboratory comparisons.
 Limited number of places still available.

15. Acknowledgements
We gratefully acknowledge the financial sponsorship of
safefood in facilitating attendance at the Method Validation in
Analytical Science: Current Practices and Future Challenges
workshop in Ghent, May 2016.