Adsorbed protein film on pump surfaces leads to particle formation during fill-finish manufacturing.
aggregation
ceramic rotary piston pump
filling
particle formation
protein adsorption
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
29
03
2021
received:
12
12
2020
accepted:
15
04
2021
pubmed:
30
4
2021
medline:
18
1
2022
entrez:
29
4
2021
Statut:
ppublish
Résumé
During fill-finish manufacturing, therapeutic proteins may aggregate or form subvisible particles in response to the physical stresses encountered within filling pumps. Understanding and quantitating this risk is important since filling may be the last unit operation before the patient receives their dose. We studied particle formation from lab-scale to manufacturing-scale using sensitive and robust protein formulations. Filling experiments with a ceramic rotary piston pump were integrated with a rinse-stripping method to investigate the relationship between protein adsorption and particle formation. For a sensitive protein, multilayer film formation on the piston surface correlated with high levels of subvisible particles in solution. For a robust protein formulation, adsorption and subvisible particle formation were minimal. These results support an aggregation mechanism that is initiated by adsorption to pump surfaces and propagated by mechanical and/or hydrodynamic disruption of the film. The elemental analysis confirmed that ceramic wear debris remained at trace levels and did not contribute appreciably to protein aggregation.
Substances chimiques
Membranes, Artificial
0
Protein Aggregates
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2947-2957Informations de copyright
© 2021 Wiley Periodicals LLC.
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