A phase diagram-based toolbox to assess the impact of freeze/thaw ramps on the phase behavior of proteins

The influence of process parameters during freeze/thaw (FT) operations is essential for the preservation of the protein stability/activity during production and storage processes in the biopharmaceutical industry. Process parameters, such as FT ramps, the final storage time and temperature, affect t...

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Bibliographic Details
Published in:Bioprocess and biosystems engineering 2020-02, Vol.43 (2), p.179-192
Main Authors: Wöll, Anna Katharina, Desombre, Monika, Enghauser, Lena, Hubbuch, Jürgen
Format: Article
Language:English
Subjects:
Biopharmaceuticals
Biotechnology
Chemistry
Chemistry and Materials Science
Crystal morphology
Denaturation
Environmental Engineering/Biotechnology
Food Science
Freeze-thawing
Glass transition temperature
Ice crystals
Ice formation
Industrial and Production Engineering
Industrial Chemistry/Chemical Engineering
Phase diagrams
Preservation
Process parameters
Protein interaction
Proteins
Ramps
Research Paper
Stability
Temperature
Transition temperatures
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Summary:The influence of process parameters during freeze/thaw (FT) operations is essential for the preservation of the protein stability/activity during production and storage processes in the biopharmaceutical industry. Process parameters, such as FT ramps, the final storage time and temperature, affect the occurring FT stress onto the target protein in different ways. FT stress includes cold denaturation, freeze concentration, and ice crystal formation which can result in protein aggregation. To visualize the impact of variations in FT ramps, descriptors such as solubility, phase behavior and crystal morphology were evaluated. The phase diagram-based toolbox in combination with an HTS-compatible cryo-device allowed the identification of suitable ramping schemes during FT operations. It could be clearly shown that rapid operations are needed above the glass transition temperature of the target protein to circumvent precipitation during FT cycles. Finally, a stability index is introduced which allows ranking of the systems investigated. Graphic abstract
ISSN:1615-7591
1615-7605
DOI:10.1007/s00449-019-02215-5