PAT For Freeze Drying: Cycle Optimization In The Laboratory

By Dr. Henning Gieseler, PhD., Department of Pharmaceutics, University of Erlangen-Nuremberg

Freeze drying is generally known to be a time consuming and therefore expensive process. In order to lower costs during manufacturing, the effective cycle time must be reduced. This goal can be achieved by optimising a freeze drying cycle in the laboratory – in particular the primary drying phase. Applying PAT in the laboratory can provide valuable information about product and process behaviour and may help to identify the critical process parameters during cycle development and optimisation.

The pharmaceutical industry and the FDA have come to realise that testing quality in the final product is inhibiting the rate of introducing important new drugs. During the past few years the FDA has formulated an important new initiative intended to modernise pharmaceutical manufacturing and encourage pharmaceutical manufacturers to use PAT. The FDA has indicated that drug manufacturers who adopt advanced process monitoring and control techniques may receive favourable treatment from them1,2. The goal of the initiative is to enable manufacturers to produce drug products more efficiently and with higher quality. To be capable of producing more efficiently in manufacturing while still assuring product quality means that critical process parameters (CPPs) must be specified and controlled within predefined limits (design space).

These specifications, however, must be set by performing experiments in the laboratory and using PAT tools that are capable of describing all of the important process parameters with acceptable accuracy. PAT is a tool-box which includes the use of ‘smart’ sensors that may enhance process monitoring and process understanding during development as well as process monitoring and control during commercial manufacture. It is important to underline that PAT in the laboratory is more focussed on process understanding, i.e. PAT tools should enable a more detailed scientific approach to product and process development in the laboratory (Quality by Design, QbD). It is mandatory to identify and correlate the critical process parameters relative to quality attributes for a particular product in the early phase of formulation and process development and then to control these parameters during manufacturing.