Abstract
The NISTmAb is a monoclonal antibody Reference Material from the National Institute of Standards and Technology; it is a class-representative IgG1κ intended serve as a pre-competitive platform for harmonization and technology development in the biopharmaceutical industry. The publication series of which this paper is a part describes NIST’s overall control strategy to ensure NISTmAb quality and availability over its lifecycle. In this paper, the development and qualification of methods for monitoring NISTmAb charge heterogeneity are described. Capillary zone electrophoresis (CZE) and capillary isoelectric focusing (CIEF) assays were optimized and evaluated as candidate assays for NISTmAb quality control. CIEF was found to be suitable as a structural characterization assay yielding information on the apparent pI of the NISTmAb. CZE was found to be better suited for routine monitoring of NISTmAb charge heterogeneity and was qualified for this purpose. This paper is intended to provide relevant details of NIST’s charge heterogeneity control strategy to facilitate implementation of the NISTmAb as a test molecule in the end user’s laboratory.Graphical Representative capillary zone electropherogram of the NIST monoclonal antibody (NISTmAb). The NISTmAb is a publicly available research tool intended to facilitate advancement of biopharmaceutical analytics.
Highlights
Complex biotherapeutics, in particular monoclonal antibodies, increasingly dominate the arena of new drugs submitted for regulatory approval
We describe the development and qualification of charge heterogeneity monitoring assays based on capillary electrophoresis, which form an integral part of the quality control strategy of the NISTmAb Reference Material
capillary isoelectric focusing (CIEF) method development CIEF separates charge variants based on differences in isoelectric point [29]
Summary
In particular monoclonal antibodies, increasingly dominate the arena of new drugs submitted for regulatory approval. Increased knowledge surrounding fundamental measurement principles of each measurement can lead to better, more streamlined product characterization and will facilitate new technology and product development With this need in mind, NIST developed Reference Material 8671 (BNISTmAb^), a class-representative humanized IgG1κ monoclonal antibody which has undergone extensive analytical and biophysical characterization by NIST and industry/academic/ government stakeholders [4,5,6,7,8,9,10,11,12,13,14,15]. The NISTmAb is intended to serve as a platform for open innovation and technology development through evaluation of established and novel analytical methods In support of this goal, NIST has an ongoing characterization and quality monitoring program using stateof-the-art analytical methods to contribute to a growing opensource knowledge base surrounding the NISTmAb. Here, we describe the development and qualification of charge heterogeneity monitoring assays based on capillary electrophoresis, which form an integral part of the quality control strategy of the NISTmAb Reference Material.
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