Development of orthogonal NISTmAb size heterogeneity control methods

Area of Science:

• Biopharmaceutical Analytics
• Analytical Chemistry
• Quality Control

Background:

• The National Institute of Standards and Technology (NIST) developed the NISTmAb, a monoclonal antibody reference material.
• The NISTmAb serves as a platform for harmonizing analytical methods and developing new technologies in the biopharmaceutical industry.
• Ensuring the quality and availability of the NISTmAb throughout its lifecycle is critical.

Purpose of the Study:

• To develop and describe a control strategy for monitoring size heterogeneity of the NISTmAb.
• To optimize and qualify analytical methods for measuring size heterogeneity across a wide size range.
• To provide details for implementing the NISTmAb as a test molecule in end-user laboratories.

Main Methods:

• Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) for size heterogeneity analysis.
• Size exclusion chromatography (SEC) to assess molecular size distribution.
• Dynamic light scattering (DLS) for particle size measurements.
• Flow imaging analysis for visualizing and quantifying particle characteristics.

Main Results:

• Optimization and qualification of multiple analytical techniques for size heterogeneity measurement.
• Establishment of a comprehensive control strategy for NISTmAb size heterogeneity.
• Demonstration of the NISTmAb's suitability as a reference material for analytical method development.

Conclusions:

• The developed control strategy effectively monitors NISTmAb size heterogeneity.
• The NISTmAb is a valuable tool for advancing biopharmaceutical analytical methods.
• Implementation of this strategy facilitates the use of NISTmAb in diverse laboratory settings.