Using enhanced development tools offered by analytical Quality by Design to support switching of a quality control...

Area of Science:

• Pharmaceutical Analysis
• Analytical Chemistry
• Biotechnology

Background:

• Quality by Design (QbD) principles are vital in pharmaceutical development.
• Traditional SDS-polyacrylamide gel electrophoresis (SDS-PAGE) has limitations for monoclonal antibody analysis.
• Analytical QbD (AQbD) offers a systematic approach to method development.

Purpose of the Study:

• To develop a capillary electrophoresis sodium dodecyl sulfate under reducing conditions (rCE-SDS) method.
• To replace the existing SDS-polyacrylamide gel electrophoresis (SDS-PAGE) method for product release and stability testing.
• To ensure the new method is robust and maintains data integrity.

Main Methods:

• Defined analytical target profile (ATP) and performance requirements.
• Conducted systematic risk assessments of method parameters.
• Utilized design of experiments (DoE) to establish a method operable design region (MODR).
• Performed a bridging study to compare rCE-SDS with SDS-PAGE.

Main Results:

• The AQbD approach identified critical method parameters and established an MODR.
• The rCE-SDS method demonstrated increased sensitivity compared to SDS-PAGE.
• A conversion factor was established to correlate historical and new method data.
• Method robustness was significantly improved.

Conclusions:

• Systematic AQbD application elucidated complex input-output relationships for analytical methods.
• Linking method performance to product quality attributes is key for de-risking analytical method transitions.
• The developed rCE-SDS method is suitable for replacing SDS-PAGE in monoclonal antibody control strategies.