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Anal Bioanal Chem. 2018 Mar;410(8):2095-2110. doi: 10.1007/s00216-017-0819-3. Epub 2018 Feb 10.

Development of orthogonal NISTmAb size heterogeneity control methods.

Author information

1
National Institute of Standards and Technology, Institute for Bioscience and Biotechnology Research, 9600 Gudelsky Dr, Rockville, MD, 20850, USA.
2
MedImmune, LLC, 55 Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
3
National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, MD, 20899, USA.
4
National Institute of Standards and Technology, Institute for Bioscience and Biotechnology Research, 9600 Gudelsky Dr, Rockville, MD, 20850, USA. john.schiel@nist.gov.

Abstract

The NISTmAb is a monoclonal antibody Reference Material from the National Institute of Standards and Technology; it is a class-representative IgG1κ intended to 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 of a control strategy for monitoring NISTmAb size heterogeneity is described. Optimization and qualification of size heterogeneity measurement spanning a broad size range are described, including capillary electrophoresis-sodium dodecyl sulfate (CE-SDS), size exclusion chromatography (SEC), dynamic light scattering (DLS), and flow imaging analysis. This paper is intended to provide relevant details of NIST's size heterogeneity control strategy to facilitate implementation of the NISTmAb as a test molecule in the end user's laboratory. Graphical abstract Representative size exclusion chromatogram of the NIST monoclonal antibody (NISTmAb). The NISTmAb is a publicly available research tool intended to facilitate advancement of biopharmaceutical analytics. HMW = high molecular weight (trimer and dimer), LMW = low molecular weight (2 fragment peaks). Peak labeled buffer is void volume of the column from L-histidine background buffer.

KEYWORDS:

Aggregation; Biopharmaceutical; Biosimilar; Biotherapeutic; Capillary electrophoresis; Monoclonal antibody; NISTmAb; Protein particle; Reference material; System suitability

PMID:
29428991
PMCID:
PMC5830496
DOI:
10.1007/s00216-017-0819-3
[Indexed for MEDLINE]
Free PMC Article

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