Journal ArticleDOI
Subvisible Particulate Matter in Therapeutic Protein Injections
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TLDR
The particle properties can be used to assess the risk associated with protein aggregates in the drug and to study their possible formation mechanisms, and could be useful during drug development and manufacturing to reduce the particulate matter content.Abstract:
Strategies for determining particulate matter in therapeutic protein injections, including extrinsic and intrinsic particles, are reviewed. Special attention is devoted to the advantages and limitations of various methods used for these purposes, each of which enables different particle characteristics to be determined. The source of particles (extrinsic, intrinsic, or inherent) can be understood better and particle-size distribution and other characteristics can be studied and used to differentiate them if methods based on different measurement principles are used. Protein aggregates in drugs have broad particle-size distributions, from oligomers to particles reaching hundreds of microns. The particle properties can be used to assess the risk associated with protein aggregates in the drug and to study their possible formation mechanisms. Such information could be useful during drug development and manufacturing to reduce the particulate matter content.read more
Citations
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Journal ArticleDOI
Interfacial Stress in the Development of Biologics: Fundamental Understanding, Current Practice, and Future Perspective.
Jinjiang Li,Mary Elizabeth Krause,Xiaodong Chen,Yuan Cheng,Weiguo Dai,John J. Hill,Min Huang,Susan Jordan,Daniel LaCasse,Linda O. Narhi,Evgenyi Shalaev,Ian C. Shieh,Justin C. Thomas,Raymond S. Tu,Songyan Zheng,Lily Zhu +15 more
TL;DR: A high-level mechanistic understanding of the relationship between interfacial stress and aggregation will be introduced, as well as some novel techniques for measuring and better understanding the interfacial behavior of proteins.
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Freezing-induced protein aggregation - Role of pH shift and potential mitigation strategies.
TL;DR: The protein, by inhibiting buffer crystallization, prevented the pH shift and then the buffer, by maintaining the pH, enhanced protein stability.
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Excipients for Room Temperature Stable Freeze-Dried Monoclonal Antibody Formulations.
TL;DR: It is concluded that the addition of CD allows for shorter freeze-drying cycles with improved cake appearance and enables storage at room temperature, which might reduce costs of goods substantially.
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A Comprehensive Assessment of All-Oleate Polysorbate 80: Free Fatty Acid Particle Formation, Interfacial Protection and Oxidative Degradation.
Nidhi Doshi,Jamie Giddings,Lin Luis,Arthur Wu,Kyle Ritchie,Wenqiang Liu,Wayman Chan,Rosalynn Taing,Jeff Chu,Alavattam Sreedhara,Aadithya Kannan,Pervina Kei,Ian C. Shieh,Tobias Graf,Mark Hu +14 more
TL;DR: In this article, the authors evaluated the homogeneous all-oleate (AO) PS80 alongside heterogeneous PS20 and PS80 grades in terms of their propensity to form free fatty acid (FFA) particles.
Journal ArticleDOI
A Multicompany Assessment of Submicron Particle Levels by NTA and RMM in a Wide Range of Late-Phase Clinical and Commercial Biotechnology-Derived Protein Products.
Mario Hubert,Dennis T. Yang,Stanley C. Kwok,Anacelia Rios,Tapan K. Das,Ankit R. Patel,Klaus Wuchner,Valentyn Antochshuk,Friederike Junge,George M. Bou-Assaf,Shawn Cao,Miguel Saggu,Luis Montrond,Nataliya Afonina,Parag Kolhe,Vakhtang Loladze,Linda O. Narhi +16 more
TL;DR: Results suggest that NTA and RMM-based techniques can be used during product and process characterization, contributing information on the nature and propensity for formation of submicron particles and what is normal for the product, but may not be suitable for release or quality control testing.
References
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Journal ArticleDOI
Overlooking subvisible particles in therapeutic protein products: Gaps that may compromise product quality
John F. Carpenter,Theodore W. Randolph,Wim Jiskoot,Daan J.A. Crommelin,C. Russell Middaugh,Gerhard Winter,Ying-Xin Fan,Susan L. Kirshner,Daniela Verthelyi,Steven Kozlowski,Kathleen A. Clouse,Patrick G. Swann,Amy S. Rosenberg,Barry Cherney +13 more
TL;DR: The purpose of this commentary is to provide brief summaries on the factors affecting protein aggregation and the key aspects of protein aggregation that are associated with immunogenicity, and emphasize the current scientific gaps in understanding and analytical limitations for quantitation of species of large protein aggregates that are referred to as subvisible particles.
Journal ArticleDOI
An Industry Perspective on the Monitoring of Subvisible Particles as a Quality Attribute for Protein Therapeutics
Satish K. Singh,Nataliya Afonina,Michel Awwad,Karoline Bechtold-Peters,Jeffrey T. Blue,Danny K. Chou,Mary E.M. Cromwell,Hans-Juergen Krause,Hanns-Christian Mahler,Brian K. Meyer,Linda O. Narhi,Doug P. Nesta,Thomas Spitznagel +12 more
TL;DR: It is emphasized that the link between aggregation and clinical immunogenicity has not been unequivocally established; and that such particles are present in marketed products which remain safe and efficacious despite the lack of monitoring.
Journal ArticleDOI
Classification of protein aggregates
TL;DR: This paper proposed a standardized nomenclature and classification scheme that can be applied to describe all protein aggregates, including size, reversibility/dissociation, conformation, cova- lent modification, and morphology.
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