Controlling Ice Nucleation during Lyophilization: Process Optimization of Vacuum-Induced Surface Freezing

Andrea Allmendinger; Yuen Li Butt; Raphael Mietzner; Felix Schmidt; Joerg Luemkemann; Carmen Lema Martinez

LAPSE

Living Archive for Process Systems Engineering

LAPSE:2021.0255

Published Article

LAPSE:2021.0255

Controlling Ice Nucleation during Lyophilization: Process Optimization of Vacuum-Induced Surface Freezing

Andrea Allmendinger, Yuen Li Butt, Raphael Mietzner, Felix Schmidt, Joerg Luemkemann, Carmen Lema Martinez

April 27, 2021

Biopharmaceuticals are often lyophilized to improve their storage stability. Controlling ice nucleation during the freezing step of the lyophilization process is desired to increase homogeneity of product properties across a drug product batch and shorten the primary drying time. The present communication summarizes the process optimization of the freezing process when using vacuum-induced surface freezing to control ice nucleation, in particular for amorphous samples. We characterized freeze-dried samples for solid state properties, and compared these to uncontrolled nucleated samples using bovine serum albumin (BSA) as a model protein. Freezing parameters were optimized to obtain complete nucleation, adequate cake resistance during the subsequent lyophilization cycle, and elegant cakes. We highlight the challenges associated with vacuum-induced surface freezing and propose optimized freezing parameters to control ice nucleation, enabling manufacturing of amorphous samples.

Record ID

LAPSE:2021.0255

Keywords

amorphous, controlled ice nucleation, freeze-drying, lyophilization, protein formulations, sucrose

Subject

Process Design

Suggested Citation

Allmendinger A, Butt YL, Mietzner R, Schmidt F, Luemkemann J, Lema Martinez C. Controlling Ice Nucleation during Lyophilization: Process Optimization of Vacuum-Induced Surface Freezing. (2021). LAPSE:2021.0255

Author Affiliations

Allmendinger A: Pharmaceutical Development & Supplies, Biologics Europe, F. Hoffmann-La Roche, Grenzacherstr. 124, CH-4070 Basel, Switzerland; Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Freiburg, Hermann-H [ORCID]
Butt YL: Pharmaceutical Development & Supplies, Biologics Europe, F. Hoffmann-La Roche, Grenzacherstr. 124, CH-4070 Basel, Switzerland; Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Freiburg, Hermann-H
Mietzner R: Pharmaceutical Development & Supplies, Biologics Europe, F. Hoffmann-La Roche, Grenzacherstr. 124, CH-4070 Basel, Switzerland [ORCID]
Schmidt F: Pharmaceutical Development & Supplies, Biologics Europe, F. Hoffmann-La Roche, Grenzacherstr. 124, CH-4070 Basel, Switzerland
Luemkemann J: Pharmaceutical Development & Supplies, Biologics Europe, F. Hoffmann-La Roche, Grenzacherstr. 124, CH-4070 Basel, Switzerland
Lema Martinez C: Pharmaceutical Development & Supplies, Biologics Europe, F. Hoffmann-La Roche, Grenzacherstr. 124, CH-4070 Basel, Switzerland

Journal Name

Processes

Volume

8

Issue

10

Article Number

E1263

Year

2020

Publication Date

2020-10-08