Multi-attribute PAT for UF/DF of Proteins-Monitoring Concentration, particle sizes, and Buffer Exchange.
Aggregation
Light scattering
PAT
Sub-visible particles
UF/DF
UV/Vis spectroscopy
Journal
Analytical and bioanalytical chemistry
ISSN: 1618-2650
Titre abrégé: Anal Bioanal Chem
Pays: Germany
ID NLM: 101134327
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
29
08
2019
accepted:
03
12
2019
revised:
25
10
2019
pubmed:
20
2
2020
medline:
15
12
2020
entrez:
20
2
2020
Statut:
ppublish
Résumé
Ultrafiltration/diafiltration (UF/DF) plays an important role in the manufacturing of biopharmaceuticals. Monitoring critical process parameters and quality attributes by process analytical technology (PAT) during those steps can facilitate process development and assure consistent quality in production processes. In this study, a lab-scale cross-flow filtration (CFF) device was equipped with a variable pathlength (VP) ultraviolet and visible (UV/Vis) spectrometer, a light scattering photometer, and a liquid density sensor (microLDS). Based on the measured signals, the protein concentration, buffer exchange, apparent molecular weight, and hydrodynamic radius were monitored. The setup was tested in three case studies. First, lysozyme was used in an UF/DF run to show the comparability of on-line and off-line measurements. The corresponding correlation coefficients exceeded 0.97. Next, urea-induced changes in protein size of glucose oxidase (GOx) were monitored during two DF steps. Here, correlation coefficients were ≥ 0.92 for static light scattering (SLS) and dynamic light scattering (DLS). The correlation coefficient for the protein concentration was 0.82, possibly due to time-dependent protein precipitation. Finally, a case study was conducted with a monoclonal antibody (mAb) to show the full potential of this setup. Again, off-line and on-line measurements were in good agreement with all correlation coefficients exceeding 0.92. The protein concentration could be monitored in-line in a large range from 3 to 120 g L
Identifiants
pubmed: 32072210
doi: 10.1007/s00216-019-02318-8
pii: 10.1007/s00216-019-02318-8
doi:
Substances chimiques
Antibodies, Monoclonal
0
Buffers
0
Proteins
0
Glucose Oxidase
EC 1.1.3.4
Muramidase
EC 3.2.1.17
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2123-2136Références
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