Protocol for Verification of Bioanalytical Method Performance in BA/BE Studies

Purpose

The purpose of this Standard Operating Procedure (SOP) is to establish guidelines for the cross-validation of bioanalytical methods used in Bioavailability (BA) and Bioequivalence (BE) studies, ensuring accuracy, reliability, and consistency of analytical results.

Scope

This SOP applies to all study personnel involved in the development, validation, and implementation of bioanalytical methods for the quantification of drug concentrations in biological samples, including Laboratory Analysts, Data Managers, and Quality Assurance Personnel.

Responsibilities

• The Laboratory Analyst is responsible for performing cross-validation experiments to compare the performance of bioanalytical methods across different laboratories, instruments, and operators.
• The Data Manager is responsible for analyzing and interpreting cross-validation data, assessing method agreement and variability, and documenting results for review and approval.
• The Quality Assurance Personnel is responsible for overseeing the cross-validation process, reviewing and approving validation protocols, and ensuring compliance with regulatory requirements and quality standards.

Procedure

1. Develop a cross-validation protocol outlining the objectives, experimental design, acceptance criteria, and statistical methods for evaluating the performance of bioanalytical methods across different laboratories, instruments, and operators.
2. Select representative test samples containing known concentrations of analytes of interest and distribute them to participating laboratories for analysis using their respective bioanalytical methods.
3. Perform cross-validation experiments according to the protocol, analyzing test samples in duplicate or triplicate using each method, and documenting all experimental details, including sample preparation, instrument parameters, and analytical procedures.
4. Compare the results obtained from different laboratories, instruments, and operators using statistical methods such as regression analysis, Bland-Altman plots, and calculation of correlation coefficients, to assess method agreement, bias, and variability.
5. Evaluate the accuracy, precision, specificity, and sensitivity of each bioanalytical method based on cross-validation data, comparing performance metrics against predefined acceptance criteria and regulatory guidelines.
6. Document all cross-validation activities, including experimental protocols, raw data, statistical analyses, and interpretation of results, in validation reports and study documentation, for review and approval by Quality Assurance Personnel.
7. Implement corrective actions and process improvements based on cross-validation findings, addressing any deficiencies or discrepancies identified in method performance, to ensure continuous improvement and adherence to best practices.

Abbreviations

• SOP – Standard Operating Procedure
• BA – Bioavailability
• BE – Bioequivalence

Documents

• Cross-validation Protocol
• Validation Reports
• Statistical Analysis Summary
• Corrective Action Reports

Reference

International Council for Harmonisation (ICH) E6 Good Clinical Practice guidelines and relevant regulatory guidelines for bioanalytical method validation and cross-validation in clinical research.

SOP Version

Version 1.0