In silico process characterization for biopharmaceutical development following the quality by design concept.
antibody purification
cation exchange chromatography
in silico process characterization
mechanistic chromatography modeling
Journal
Biotechnology progress
ISSN: 1520-6033
Titre abrégé: Biotechnol Prog
Pays: United States
ID NLM: 8506292
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
06
07
2021
received:
09
06
2021
accepted:
21
07
2021
pubmed:
27
7
2021
medline:
26
3
2022
entrez:
26
7
2021
Statut:
ppublish
Résumé
With the quality by design (QbD) initiative, regulatory authorities demand a consistent drug quality originating from a well-understood manufacturing process. This study demonstrates the application of a previously published mechanistic chromatography model to the in silico process characterization (PCS) of a monoclonal antibody polishing step. The proposed modeling workflow covered the main tasks of traditional PCS studies following the QbD principles, including criticality assessment of 11 process parameters and establishment of their proven acceptable ranges of operation. Analyzing effects of multi-variate sampling of process parameters on the purification outcome allowed identification of the edge-of-failure. Experimental validation of in silico results demanded approximately 75% less experiments compared to a purely wet-lab based PCS study. Stochastic simulation, considering the measured variances of process parameters and loading material composition, was used to estimate the capability of the process to meet the acceptance criteria for critical quality attributes and key performance indicators. The proposed workflow enables the implementation of digital process twins as QbD tool for improved development of biopharmaceutical manufacturing processes.
Substances chimiques
Antibodies, Monoclonal
0
Biological Products
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3196Informations de copyright
© 2021 The Authors. Biotechnology Progress published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.
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