Design & Optimization of Freeze-Drying Cycles: Scientific Based Cycle Design, Robustness Testing & Sources of Errors

Design of freeze-drying processes is often approached with a “trial and error” procedure when scientists are new to the subject. In some cases, the freeze-drying recipe used in the first laboratory experiment is used without any further refinement or optimization. Consequently, commercial freeze-drying processes are often neither robust nor efficient. 

This presentation is divided into three chapters. In chapter one, the design of an “optimized” freeze-drying process is presented using some simple guidelines which are based on well-accepted scientific principles. This chapter discusses the impact of freezing and representative freezing protocols. It further highlights the significance of the formulation collapse temperature and selection of a “target product temperature” (Ttarget) during primary drying, along with guidelines for selection of the optimum shelf temperature and chamber pressure to get to Ttarget. Lastly, rules for secondary drying are being discussed. 

In the following chapter, “robustness testing” as part of a QbD approach is discussed using a reduced experimental design. The procedure can guide an inexperienced scientist to better understand the link between product and process. A vaccine formulation is used as an example to illustrate robustness testing in practice. 

In the last chapter, typical sources of errors during freeze-drying will be illustrated by some real-world examples, and their root causes will be briefly discussed.

Henning Gieseler, former CEO and currently CSO at GILYOS GmbH, adjunct professor at the Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Julius-Maximilians University (JMU) Würzburg, received his Ph.D. in pharmaceutics from the FAU Erlangen-Nürnberg in 2004, was appointed as a postdoc at the University of Connecticut under supervision of Dr. Michael Pikal 2004 to 2006 and received his habilitation and venia legend in pharmaceutical technology and biopharmacy at FAU Erlangen-Nürnberg in 2010. In the same year he founded GILYOS GmbH.