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Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering

Biopharmaceuticals are large, complex and labile therapeutic molecules prone to instability due to various factors during manufacturing. To ensure their safety, quality and efficacy, a wide range of critical quality attributes (CQAs) such as product concentration, aggregation, particle size, purity...

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Autores principales: Sharma, Ashutosh, Beirne, Jason, Khamar, Dikshitkumar, Maguire, Ciaran, Hayden, Ambrose, Hughes, Helen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10033178/
https://www.ncbi.nlm.nih.gov/pubmed/36949219
http://dx.doi.org/10.1208/s12249-023-02529-4
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author Sharma, Ashutosh
Beirne, Jason
Khamar, Dikshitkumar
Maguire, Ciaran
Hayden, Ambrose
Hughes, Helen
author_facet Sharma, Ashutosh
Beirne, Jason
Khamar, Dikshitkumar
Maguire, Ciaran
Hayden, Ambrose
Hughes, Helen
author_sort Sharma, Ashutosh
collection PubMed
description Biopharmaceuticals are large, complex and labile therapeutic molecules prone to instability due to various factors during manufacturing. To ensure their safety, quality and efficacy, a wide range of critical quality attributes (CQAs) such as product concentration, aggregation, particle size, purity and turbidity have to be met. Size exclusion chromatography (SEC) is the gold standard to measure protein aggregation and degradation. However, other techniques such as dynamic light scattering (DLS) are employed in tandem to measure the particle size distribution (PSD) and polydispersity of biopharmaceutical formulations. In this study, the application of multi-angle dynamic light scattering (MADLS) was evaluated for the determination of particle size, particle concentration and aggregation in 3 different protein modalities, namely bovine serum albumin (BSA) and two biopharmaceuticals including a monoclonal antibody (mAb) and an enzyme. The obtained calibration curve (R(2) > 0.95) for the particle number concentration of the 3 proteins and the observed correlation between MADLS and SEC (R(2) = 0.9938) for the analysis of aggregation in the enzyme can be employed as a 3-in-1 approach to assessing particle size, concentration and aggregation for the screening and development of products while also reducing the number of samples and experiments required for analysis prior to other orthogonal tests. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1208/s12249-023-02529-4.
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spelling pubmed-100331782023-03-23 Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering Sharma, Ashutosh Beirne, Jason Khamar, Dikshitkumar Maguire, Ciaran Hayden, Ambrose Hughes, Helen AAPS PharmSciTech Research Article Biopharmaceuticals are large, complex and labile therapeutic molecules prone to instability due to various factors during manufacturing. To ensure their safety, quality and efficacy, a wide range of critical quality attributes (CQAs) such as product concentration, aggregation, particle size, purity and turbidity have to be met. Size exclusion chromatography (SEC) is the gold standard to measure protein aggregation and degradation. However, other techniques such as dynamic light scattering (DLS) are employed in tandem to measure the particle size distribution (PSD) and polydispersity of biopharmaceutical formulations. In this study, the application of multi-angle dynamic light scattering (MADLS) was evaluated for the determination of particle size, particle concentration and aggregation in 3 different protein modalities, namely bovine serum albumin (BSA) and two biopharmaceuticals including a monoclonal antibody (mAb) and an enzyme. The obtained calibration curve (R(2) > 0.95) for the particle number concentration of the 3 proteins and the observed correlation between MADLS and SEC (R(2) = 0.9938) for the analysis of aggregation in the enzyme can be employed as a 3-in-1 approach to assessing particle size, concentration and aggregation for the screening and development of products while also reducing the number of samples and experiments required for analysis prior to other orthogonal tests. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1208/s12249-023-02529-4. Springer International Publishing 2023-03-22 /pmc/articles/PMC10033178/ /pubmed/36949219 http://dx.doi.org/10.1208/s12249-023-02529-4 Text en © The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Research Article
Sharma, Ashutosh
Beirne, Jason
Khamar, Dikshitkumar
Maguire, Ciaran
Hayden, Ambrose
Hughes, Helen
Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering
title Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering
title_full Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering
title_fullStr Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering
title_full_unstemmed Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering
title_short Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering
title_sort evaluation and screening of biopharmaceuticals using multi-angle dynamic light scattering
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10033178/
https://www.ncbi.nlm.nih.gov/pubmed/36949219
http://dx.doi.org/10.1208/s12249-023-02529-4
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