Identification, characterization and control of a sequence variant in monoclonal antibody drug product: a case study

Abstract Sequence variants (SV) in protein bio therapeutics can be categorized as unwanted impurities and may raise serious concerns in efficacy and safety of the product. Early detection of specific sequence modifications, that can result in altered physicochemical and or biological properties, is...

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Autores principales:	Anushikha Thakur, Rekha Nagpal, Avik Kumar Ghosh, Deepak Gadamshetty, Sirisha Nagapattinam, Malini Subbarao, Shreshtha Rakshit, Sneha Padiyar, Suma Sreenivas, Nagaraja Govindappa, Harish V. Pai, Ramakrishnan Melarkode Subbaraman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5e77fcb98c3d4da6a2b92852977e8e65
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spelling	oai:doaj.org-article:5e77fcb98c3d4da6a2b92852977e8e652021-12-02T16:05:54ZIdentification, characterization and control of a sequence variant in monoclonal antibody drug product: a case study10.1038/s41598-021-92338-12045-2322https://doaj.org/article/5e77fcb98c3d4da6a2b92852977e8e652021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92338-1https://doaj.org/toc/2045-2322Abstract Sequence variants (SV) in protein bio therapeutics can be categorized as unwanted impurities and may raise serious concerns in efficacy and safety of the product. Early detection of specific sequence modifications, that can result in altered physicochemical and or biological properties, is therefore desirable in product manufacturing. Because of their low abundance, and finite resolving power of conventional analytical techniques, they are often overlooked in early drug development. Here, we present a case study where trace amount of a sequence variant is identified in a monoclonal antibody (mAb) based therapeutic protein by LC–MS/MS and the structural and functional features of the SV containing mAb is assessed using appropriate analytical techniques. Further, a very sensitive selected reaction monitoring (SRM) technique is developed to quantify the SV which revealed both prominent and inconspicuous nature of the variant in process chromatography. We present the extensive characterization of a sequence variant in protein biopharmaceutical and first report on control of sequence variants to < 0.05% in final drug product by utilizing SRM based mass spectrometry method during the purification steps.Anushikha ThakurRekha NagpalAvik Kumar GhoshDeepak GadamshettySirisha NagapattinamMalini SubbaraoShreshtha RakshitSneha PadiyarSuma SreenivasNagaraja GovindappaHarish V. PaiRamakrishnan Melarkode SubbaramanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-21 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anushikha Thakur Rekha Nagpal Avik Kumar Ghosh Deepak Gadamshetty Sirisha Nagapattinam Malini Subbarao Shreshtha Rakshit Sneha Padiyar Suma Sreenivas Nagaraja Govindappa Harish V. Pai Ramakrishnan Melarkode Subbaraman Identification, characterization and control of a sequence variant in monoclonal antibody drug product: a case study
description	Abstract Sequence variants (SV) in protein bio therapeutics can be categorized as unwanted impurities and may raise serious concerns in efficacy and safety of the product. Early detection of specific sequence modifications, that can result in altered physicochemical and or biological properties, is therefore desirable in product manufacturing. Because of their low abundance, and finite resolving power of conventional analytical techniques, they are often overlooked in early drug development. Here, we present a case study where trace amount of a sequence variant is identified in a monoclonal antibody (mAb) based therapeutic protein by LC–MS/MS and the structural and functional features of the SV containing mAb is assessed using appropriate analytical techniques. Further, a very sensitive selected reaction monitoring (SRM) technique is developed to quantify the SV which revealed both prominent and inconspicuous nature of the variant in process chromatography. We present the extensive characterization of a sequence variant in protein biopharmaceutical and first report on control of sequence variants to < 0.05% in final drug product by utilizing SRM based mass spectrometry method during the purification steps.
format	article
author	Anushikha Thakur Rekha Nagpal Avik Kumar Ghosh Deepak Gadamshetty Sirisha Nagapattinam Malini Subbarao Shreshtha Rakshit Sneha Padiyar Suma Sreenivas Nagaraja Govindappa Harish V. Pai Ramakrishnan Melarkode Subbaraman
author_facet	Anushikha Thakur Rekha Nagpal Avik Kumar Ghosh Deepak Gadamshetty Sirisha Nagapattinam Malini Subbarao Shreshtha Rakshit Sneha Padiyar Suma Sreenivas Nagaraja Govindappa Harish V. Pai Ramakrishnan Melarkode Subbaraman
author_sort	Anushikha Thakur
title	Identification, characterization and control of a sequence variant in monoclonal antibody drug product: a case study
title_short	Identification, characterization and control of a sequence variant in monoclonal antibody drug product: a case study
title_full	Identification, characterization and control of a sequence variant in monoclonal antibody drug product: a case study
title_fullStr	Identification, characterization and control of a sequence variant in monoclonal antibody drug product: a case study
title_full_unstemmed	Identification, characterization and control of a sequence variant in monoclonal antibody drug product: a case study
title_sort	identification, characterization and control of a sequence variant in monoclonal antibody drug product: a case study
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5e77fcb98c3d4da6a2b92852977e8e65
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Identification, characterization and control of a sequence variant in monoclonal antibody drug product: a case study

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