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

2. Aim
This workshop aimed to help you understand the principles of validation and to provide you with tools to enable you to develop or implement validation procedures.
My presentation will make you aware of some of the challenges.
It will not provide solutions to all of the challenges but rather ensure you are aware of the questions.

3. Contents What is Validation?
Information resources for developing a validation procedure.
Advantages of a harmonised approach.
Challenges:
Analytical Standards
Multiple Matrices
Measurement Uncertainty
Proficiency Tests
Ongoing verification
Revalidation
Conclusion

4. 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.

5. 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.

6. Information Resources for Developing a Validation Procedure
Resources which provide guidance:
Publications
The Fitness for Purpose of Analytical Methods. Eurachem, 2014
Training courses
This one!

7. Information Resources for Developing a Validation Procedure
There may be some publications you are required to follow/incorporate:
Will your method be accredited?
ISO 17025:2005 General Requirements for the Competence of Testing and Calibration Laboratories
INAB Policy Documents

8. Resources for Developing a Validation Procedure
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
ICH Guidelines

9. Resources for Developing a Validation Procedure
Sector specific.
May have different validation requirements.
Sometimes even the terminology is different.
CCalpha and CCbeta.
Ruggedness versus robustness.

10. Advantages of a Harmonised Approach
Validation across sectors is not harmonised.
Each approach demonstrates that the method is fit for purpose.
Does the lack of harmonisation matter?

11. 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.

12. 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

13. Challenges – Multiple Matrices
What constitutes a different matrix?
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

14. 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?

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

16. 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.

17. 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?

18. Conclusions
Validation is not an activity carried out before a method is put into use.
Validation is an ongoing process.
There are many challenges to be faced.
Awareness – can implement procedures.
Eurachem Method Validation Working Group aim to provide guidance in some of these areas.

19. 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.