Interlaboratory method validation of icIEF methodology for analysis of monoclonal antibodies

Area of Science:

• Biopharmaceutical Analysis
• Protein Characterization
• Analytical Method Validation

Background:

• Capillary electrophoresis (CE) is crucial for therapeutic monoclonal antibody (mAb) analysis, process development, and approval.
• Imaged capillary isoelectric focusing (icIEF) offers powerful quantitative monitoring of protein charge heterogeneity in mAbs.
• Existing icIEF methods lack validation for therapeutic mAbs under International Council for Harmonization (ICH) guidelines.

Purpose of the Study:

• To validate imaged capillary isoelectric focusing (icIEF) technology for therapeutic monoclonal antibodies (mAbs).
• To ensure icIEF method compliance with International Council for Harmonization (ICH) guidelines for pharmaceutical use.
• To establish standardized icIEF methods for the clinical approval of therapeutic mAbs.

Main Methods:

• Method validation of icIEF was performed according to ICH guidelines.
• Validation encompassed specificity, precision, accuracy, linearity, range, limit of quantitation (LOQ), and robustness.
• The study involved 10 laboratories across 8 independent companies using a therapeutic mAb.

Main Results:

• First-time validation of icIEF technology for therapeutic monoclonal antibodies (mAbs) was successfully achieved.
• All tested method parameters strictly adhered to ICH guideline requirements.
• The collaborative validation involved multiple independent laboratories and companies.

Conclusions:

• The validated icIEF method provides a standardized approach for therapeutic mAb analysis.
• This validation represents a significant advancement for the clinical approval process of therapeutic mAbs.
• Standardized icIEF methods will enhance the reliability and consistency of mAb characterization.