Freeze–thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics

Abstract Physical instabilities of proteins in the form of protein aggregation continue to be a major challenge in the development of protein drug candidates. Aggregation can occur during different stages of product lifecycle such as freeze–thaw, manufacturing, shipping, and storage, and can potenti...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Keethkumar Jain, Nazila Salamat-Miller, Katherine Taylor
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5f6a093b2b524b8da2bed8f3f6f2e893
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5f6a093b2b524b8da2bed8f3f6f2e893
record_format	dspace
spelling	oai:doaj.org-article:5f6a093b2b524b8da2bed8f3f6f2e8932021-12-02T17:51:13ZFreeze–thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics10.1038/s41598-021-90772-92045-2322https://doaj.org/article/5f6a093b2b524b8da2bed8f3f6f2e8932021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90772-9https://doaj.org/toc/2045-2322Abstract Physical instabilities of proteins in the form of protein aggregation continue to be a major challenge in the development of protein drug candidates. Aggregation can occur during different stages of product lifecycle such as freeze–thaw, manufacturing, shipping, and storage, and can potentially delay commercialization of candidates. A lack of clear understanding of the underlying mechanism(s) behind protein aggregation and the potential immunogenic reactions renders the presence of aggregates in biotherapeutic products undesirable. Understanding and minimizing aggregation can potentially reduce immunogenic responses and make protein therapeutics safer. Therefore, it is imperative to identify, understand, and control aggregation during early formulation development and develop reliable and orthogonal analytical methodologies to detect and monitor levels of aggregation. Freezing and thawing are typical steps involved in the manufacturing of drug product and could result in complex physical and chemical changes, which in turn could potentially cause protein aggregation. This study provides a systematic approach in understanding and selecting the ideal freeze–thaw conditions for manufacturing of protein-based therapeutics. It identifies the importance of balancing different excipients with an overall goal of sufficiently reducing or eliminating aggregation and developing a stable and scalable formulation. The results demonstrated that the freeze–thaw damage of mAb-1 in aqueous solutions was significantly reduced by identification of optimal freeze–thaw conditions using first a small-scale model with subsequent at-scale verifications. The work provides a framework for successful transfer of drug product manufacturing process from small-scale to the manufacturing scale production environment especially for molecules that are susceptible to freeze–thaw induced degradations.Keethkumar JainNazila Salamat-MillerKatherine TaylorNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Keethkumar Jain Nazila Salamat-Miller Katherine Taylor Freeze–thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics
description	Abstract Physical instabilities of proteins in the form of protein aggregation continue to be a major challenge in the development of protein drug candidates. Aggregation can occur during different stages of product lifecycle such as freeze–thaw, manufacturing, shipping, and storage, and can potentially delay commercialization of candidates. A lack of clear understanding of the underlying mechanism(s) behind protein aggregation and the potential immunogenic reactions renders the presence of aggregates in biotherapeutic products undesirable. Understanding and minimizing aggregation can potentially reduce immunogenic responses and make protein therapeutics safer. Therefore, it is imperative to identify, understand, and control aggregation during early formulation development and develop reliable and orthogonal analytical methodologies to detect and monitor levels of aggregation. Freezing and thawing are typical steps involved in the manufacturing of drug product and could result in complex physical and chemical changes, which in turn could potentially cause protein aggregation. This study provides a systematic approach in understanding and selecting the ideal freeze–thaw conditions for manufacturing of protein-based therapeutics. It identifies the importance of balancing different excipients with an overall goal of sufficiently reducing or eliminating aggregation and developing a stable and scalable formulation. The results demonstrated that the freeze–thaw damage of mAb-1 in aqueous solutions was significantly reduced by identification of optimal freeze–thaw conditions using first a small-scale model with subsequent at-scale verifications. The work provides a framework for successful transfer of drug product manufacturing process from small-scale to the manufacturing scale production environment especially for molecules that are susceptible to freeze–thaw induced degradations.
format	article
author	Keethkumar Jain Nazila Salamat-Miller Katherine Taylor
author_facet	Keethkumar Jain Nazila Salamat-Miller Katherine Taylor
author_sort	Keethkumar Jain
title	Freeze–thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics
title_short	Freeze–thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics
title_full	Freeze–thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics
title_fullStr	Freeze–thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics
title_full_unstemmed	Freeze–thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics
title_sort	freeze–thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5f6a093b2b524b8da2bed8f3f6f2e893
work_keys_str_mv	AT keethkumarjain freezethawcharacterizationprocesstominimizeaggregationandenabledrugproductmanufacturingofproteinbasedtherapeutics AT nazilasalamatmiller freezethawcharacterizationprocesstominimizeaggregationandenabledrugproductmanufacturingofproteinbasedtherapeutics AT katherinetaylor freezethawcharacterizationprocesstominimizeaggregationandenabledrugproductmanufacturingofproteinbasedtherapeutics
_version_	1718379287641325568

Freeze–thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics

Ejemplares similares