A Multi-Laboratory, Multi-Platform Analysis of the Multi-Attribute Method

多实验室、多平台多属性方法分析

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Abstract

Background/Objectives: The multi-attribute method (MAM) has found diverse use in the analytical characterization of therapeutic protein products during their development and production. As the MAM matures it has the potential to enter quality control (QC) laboratories, consolidating and replacing many less informative chromatographic techniques; however, this requires an appropriate risk assessment and understanding of method capability. Methods: A validated MAM approach was used to quantify product quality attributes (PQAs) using three different mass spectrometers across two laboratories; the results were compared to conventional hydrophilic interaction chromatography-fluorescence detection (HILIC-FLD) and cation exchange chromatography-ultraviolet (CEX-UV) techniques. Results: Stressed, long-term, and accelerated stability studies were performed, and their effects on glycosylation, deamidation, oxidation and N- and C-termini were quantified. Conclusions: Overall, the inter-instrument inter-laboratory data provided here showed important considerations for transferring methods between laboratories and establishing the correlation between the MAM and conventional data, elements which are necessary to transition the MAM to the QC environment and ultimately achieving the goal of replacing orthogonal QC methods.

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