Multi attribute method implementation using a High Resolution Mass Spectrometry platform: From sample preparation to batch analysis.

Autor: Carvalho SB; iBET, Instituto de Biologia Experimental e Tecnologica, Oeiras, Portugal.; ITQB-NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal., Gomes RA; iBET, Instituto de Biologia Experimental e Tecnologica, Oeiras, Portugal.; ITQB-NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal., Pfenninger A; Sanofi R&D, Biologics Development, Industriepark Höchst, Frankfurt am Main, Germany., Fischer M; Sanofi R&D, Biologics Development, Industriepark Höchst, Frankfurt am Main, Germany., Strotbek M; Sanofi R&D, Biologics Development, Industriepark Höchst, Frankfurt am Main, Germany., Isidro IA; iBET, Instituto de Biologia Experimental e Tecnologica, Oeiras, Portugal.; ITQB-NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal., Tugçu N; Mammalian Platform, Global CMC Development, Sanofi, Framingham, MA, United States of America., Gomes-Alves P; iBET, Instituto de Biologia Experimental e Tecnologica, Oeiras, Portugal.; ITQB-NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Jan 27; Vol. 17 (1), pp. e0262711. Date of Electronic Publication: 2022 Jan 27 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0262711
Abstrakt: Quality control of biopharmaceuticals such as monoclonal antibodies (mAbs) has been evolving and becoming more challenging as the requirements of the regulatory agencies increase due to the demanding complexity of products under evaluation. Mass Spectrometry (MS)-based methods such as the multi-attribute method (MAM) are being explored to achieve a deeper understanding of the attributes critical for the safety, efficacy, and quality of these products. MAM uses high mass accuracy/high-resolution MS data that enables the direct and simultaneous monitoring of relevant product quality attributes (PQAs, in particular, chemical modifications) in a single workflow, replacing several orthogonal methods, reducing time and costs associated with these assays. Here we describe a MAM implementation process using a QTOF high resolution platform. Method implementation was accomplished using NIST (National Institute for Standards and Technology) mAb reference material and an in-process mAb sample. PQAs as glycosylation profiles, methionine oxidation, tryptophan dioxidation, asparagine deamidation, pyro-Glu at N-terminal and glycation were monitored. Focusing on applications that require batch analysis and high-throughput, sample preparation and LC-MS parameters troubleshooting are discussed. This MAM workflow was successfully explored as reference analytical tool for comprehensive characterization of a downstream processing (DSP) polishing platform and for a comparability study following technology transfer between different laboratories.
Competing Interests: Sanofi is also sponsor of this work. Anja Pfenninger, Martina Fischer, Michaela Strotbek and Nihal Tugçu are Sanofi employees and may hold shares and/or stock options in the company. The work described in this manuscript does not relate to any patients data, products in development or marketed products. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The relevant data to understand and replicate the method implementation reported in this work are within the manuscript and its Supporting Information files. Data containing antibody sequence (owned by Sanofi) cannot be shared publicly due to legal restrictions.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje