Characterization of Freezing Processes in Drug Substance Bottles by Ice Core Sampling.
cryo-concentration
drug substance bottles
frozen storage
large-scale freezing
process characterization
Journal
AAPS PharmSciTech
ISSN: 1530-9932
Titre abrégé: AAPS PharmSciTech
Pays: United States
ID NLM: 100960111
Informations de publication
Date de publication:
07 May 2024
07 May 2024
Historique:
received:
15
02
2024
accepted:
25
04
2024
medline:
8
5
2024
pubmed:
8
5
2024
entrez:
7
5
2024
Statut:
epublish
Résumé
Freezing of biological drug substance (DS) is a critical unit operation that may impact product quality, potentially leading to protein aggregation and sub-visible particle formation. Cryo-concentration has been identified as a critical parameter to impact protein stability during freezing and should therefore be minimized. The macroscopic cryo-concentration, in the following only referred to as cryo-concentration, is majorly influenced by the freezing rate, which is in turn impacted by product independent process parameters such as the DS container, its size and fill level, and the freezing equipment. (At-scale) process characterization studies are crucial to understand and optimize freezing processes. However, evaluating cryo-concentration requires sampling of the frozen bulk, which is typically performed by cutting the ice block into pieces for subsequent analysis. Also, the large amount of product requirement for these studies is a major limitation. In this study, we report the development of a simple methodology for experimental characterization of frozen DS in bottles at relevant scale using a surrogate solution. The novel ice core sampling technique identifies the axial ice core in the center to be indicative for cryo-concentration, which was measured by osmolality, and concentrations of histidine and polysorbate 80 (PS80), whereas osmolality revealed to be a sensitive read-out. Finally, we exemplify the suitability of the method to study cryo-concentration in DS bottles by comparing cryo-concentrations from different freezing protocols (-80°C vs -40°C). Prolonged stress times during freezing correlated to a higher extent of cryo-concentration quantified by osmolality in the axial center of a 2 L DS bottle.
Identifiants
pubmed: 38714592
doi: 10.1208/s12249-024-02818-6
pii: 10.1208/s12249-024-02818-6
doi:
Substances chimiques
Ice
0
Polysorbates
0
Histidine
4QD397987E
Biological Products
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102Informations de copyright
© 2024. The Author(s).
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