Directional freezing and thawing of biologics in drug substance bottles
- Biological drug substance (DS) is typically stored frozen to increase stability. However, freezing and thawing (F/T) of DS can impact product quality and therefore F/T processes need to be controlled. Because active F/T systems for DS bottles are lacking, freezing is often performed uncontrolled in conventional freezers, and thawing at ambient temperature or using water baths. In this study, we evaluated a novel device for F/T of DS in bottles, which can be operated in conventional freezers, generating a directed air stream around bottles. We characterized the F/T geometry and process performance in comparison to passive F/T using temperature mapping and analysis of concentration gradients. The device was able to better control the F/T process by inducing directional bottom-up F/T. As a result, it reduced cryo-concentration during freezing as well as ice mound formation. However, freezing with the device was dependent on freezer performance, i.e. prolonged process times in a highly loaded freezer were accompanied by increased cryo-concentrations. Thawing was faster compared to without the device, but had no impact on concentration gradients and was slower compared to thawing in a water bath. High-performance freezers might be required to fully exploit the potential of directional freezing with this device and allow F/T process harmonization and scaling across sites.
Author: | Sarah S. Peláez, Hanns-Christian MahlerGND, Jörg HuwylerORCiDGND, Andrea AllmendingerORCiDGND |
---|---|
URN: | urn:nbn:de:hebis:30:3-866207 |
DOI: | https://doi.org/10.1016/j.ejpb.2024.114427 |
ISSN: | 0939-6411 |
Parent Title (English): | European journal of pharmaceutics and biopharmaceutics |
Publisher: | Elsevier |
Place of publication: | Amsterdam |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2024/08/09 |
Date of first Publication: | 2024/07/31 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2024/08/21 |
Tag: | Biotechnology; Controlled freezing/thawing; Cryo-concentration; Directional freezing; Drug substance bottles; Freezing and thawing; Process characterization; Process time; Temperature mapping |
Volume: | 203 |
Issue: | 114427 |
Article Number: | 114427 |
Page Number: | 12 |
Institutes: | Biochemie, Chemie und Pharmazie |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Sammlungen: | Universitätspublikationen |
Licence (German): | ![]() |