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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Interlaboratory Co-validation of a UPLC-ToF MS MAM Method for Truncations of a Fc Fusion Protein

Author(s): Gang Wu, Chuanfei Yu, Qinghe Tong, Wenbo Wang, Xi Huang, Hao Li and Lan Wang*

Volume 24, Issue 10, 2023

Published on: 02 December, 2022

Page: [1315 - 1325] Pages: 11

DOI: 10.2174/1389201024666221111160403

Price: $65

Abstract

Background: Peptide-Fc fusion proteins are inherently heterogeneous and complex molecules. Protein post-translational modifications (PTMs) or truncation can arise during manufacturing or product storage. Some of these product attributes could potentially impact the efficacy or safety of the bio-molecule and are thus classified as critical quality attributes (CQAs). These CQAs should be controlled in order to ensure manufacturing and quality consistency.

Methods: A subunit UPLC-ToF MS based MAM method was developed for identity test and quantitatively monitored two critical quality attributes (CQAs) resulting from two truncations of that fusion protein (fragment 1 and 2). Three independent laboratories are involved in the method validation according to ICH Q2(R1), ICH Q6B, FDA and NMPA guidance.

Results: This developed method fully meets the pre-defined analytical target profile (ATP), including specificity, accuracy, precision, quantitation limit, linearity, range and robustness. Three independent labs co-validate a UPLC-ToF MS based MAM method for protein drug QC release and stability testing.

Conclusion: The experimental design of method validation can be a reference for LC-HRMS-based subunit MAM methods that have been widely used in the characterization of antibodies, ADCs and other protein-based biologics. This work paves the way for implementing MAM in QC with more targeted control of product quality.

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