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New approaches to optimize freeze-drying of monoclonal antibodies
New approaches to optimize freeze-drying of monoclonal antibodies
Over the last years, serious interest in emerging next-generation freeze-drying technologies raised. One promising technology that stands out due to its proven benefits in food technology is microwave-assisted freeze-drying (MFD). As briefly outlined in section I.3.2, MFD has the potential to overcome drawbacks like long drying-times due to its volumetric heating of the entire sample. However, little is known of its feasibility for pharmaceutical applications, particularly in the field of sensitive biologicals. For this reason, the first part of this thesis, Chapter II and Chapter III, is dealing with the investigation of vial-based microwave-assisted freeze-drying concerning the applicability to standard lyophilization formulations and effects on protein stability. In Chapter II, the applicability and feasibility of this technology to different monoclonal antibody formulations and the influence on the resulting product properties are subject to investigation. Moreover, the potential for drying time savings is examined. The product quality of four different pharmaceutically relevant monoclonal antibody formulations over storage and the influence of the microwave generator on batch homogeneity are studied in Chapter III. The second part of this work, Chapter IV – Chapter VI, is dedicated to detailed investigations on open questions in controlled ice nucleation (CN) in the field of freeze-drying of biologicals. Although there have been multiple publications, reports, and case studies about CN over the last two decades, experts in the freeze-drying community are still lacking essential information on aspects of comparability of different controlled ice nucleation techniques, general good practice of process design, and how to monitor the nucleation success of a whole batch non-destructively. In Chapter IV, a case study of three relevant model formulations is presented which aims to investigate if mechanistically different controlled ice nucleation techniques in freeze-drying are comparable to each other concerning drying process performance and product quality attributes. A study analyzing factors that affect the success of CN and questions of process design are studied and discussed in Chapter V. In Chapter VI a new technological solution for control of the nucleation success using a camera-based approach is presented in a proof of concept study. Chapter VII summarizes and concludes the results of the present thesis and gives an outlook.
freeze-drying, monoclonal antibody, optimization, microwave drying, controlled ice nucleation
Gitter, Julian Hendryk
2020
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Gitter, Julian Hendryk (2020): New approaches to optimize freeze-drying of monoclonal antibodies. Dissertation, LMU München: Faculty of Chemistry and Pharmacy
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Abstract

Over the last years, serious interest in emerging next-generation freeze-drying technologies raised. One promising technology that stands out due to its proven benefits in food technology is microwave-assisted freeze-drying (MFD). As briefly outlined in section I.3.2, MFD has the potential to overcome drawbacks like long drying-times due to its volumetric heating of the entire sample. However, little is known of its feasibility for pharmaceutical applications, particularly in the field of sensitive biologicals. For this reason, the first part of this thesis, Chapter II and Chapter III, is dealing with the investigation of vial-based microwave-assisted freeze-drying concerning the applicability to standard lyophilization formulations and effects on protein stability. In Chapter II, the applicability and feasibility of this technology to different monoclonal antibody formulations and the influence on the resulting product properties are subject to investigation. Moreover, the potential for drying time savings is examined. The product quality of four different pharmaceutically relevant monoclonal antibody formulations over storage and the influence of the microwave generator on batch homogeneity are studied in Chapter III. The second part of this work, Chapter IV – Chapter VI, is dedicated to detailed investigations on open questions in controlled ice nucleation (CN) in the field of freeze-drying of biologicals. Although there have been multiple publications, reports, and case studies about CN over the last two decades, experts in the freeze-drying community are still lacking essential information on aspects of comparability of different controlled ice nucleation techniques, general good practice of process design, and how to monitor the nucleation success of a whole batch non-destructively. In Chapter IV, a case study of three relevant model formulations is presented which aims to investigate if mechanistically different controlled ice nucleation techniques in freeze-drying are comparable to each other concerning drying process performance and product quality attributes. A study analyzing factors that affect the success of CN and questions of process design are studied and discussed in Chapter V. In Chapter VI a new technological solution for control of the nucleation success using a camera-based approach is presented in a proof of concept study. Chapter VII summarizes and concludes the results of the present thesis and gives an outlook.