Challenges in Method Validation A Regulatory Laboratory Perspective

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

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.

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

What is Validation? n 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 n Demonstrates that the analytical method is Fit For Purpose.

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

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

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

Resources for Developing a Validation Procedure n Legislation q q 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. q The Water Framework Directive q ICH Guidelines

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

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

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

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

Challenges – Multiple Matrices n What constitutes a different matrix? n Different matrices/species q q q n Separate validation for each matrix/species Validate in one and show equivalency Divide into matrix types Different Maximum Residue Limit in different matrices/species q q Full validation High time, cost, manpower

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

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

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

Challenges – Revalidation n When is revalidation necessary? n Full validation or modified/abbreviated validation? q q 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?

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

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.