Lyophilization, or freeze drying, is a vital process for the pharmaceutical industry. Used routinely to produce orally disintegrating tablets with the porosity and surface area required for rapid dissolution, its primary application is for product stabilization/preservation. Lyophilization underpins the shelf life of a wide range of commercial products, including live vaccines and a growing number of new biopharmaceuticals, particularly those based on monoclonal antibodies. Around 35% of biologic drugs are currently lyophilized and this figure is projected to increase significantly in coming years . Many biological molecules are labile in the presence of water, exhibiting conformational change and degradation that affects their clinical efficacy and safety. Lyophilization removes water to levels that no longer support significant biological or chemical activity, under relatively gentle process conditions, thereby preserving the integrity of the therapeutic active. It produces a dried ‘cake’ that is reconstituted at the point of use to give a formulation for parenteral administration.
The development and scale-up of a successful lyophilized product is complex, calling for careful consideration of both the formulation and processing conditions. Lyophilization technology has remained essentially unchanged over many decades and today it is one of the most expensive and time-consuming processes associated with pharmaceutical manufacture, with cycle times of up to 50 hours and energy efficiencies as low as 5% . There is significant pressure to improve process performance within the constraints of avoiding product damage and meeting validated specifications for water content. Adopting a more knowledge-led approach to lyophilization, based on a sound understanding of the underlying science is becoming increasingly important.
In this whitepaper we examine one of the Critical Quality Attributes (CQA) of lyophilized products – the surface area of the cake. We consider its importance, within the context of clinical efficacy and for process optimization, and its value in improving understanding and control of the lyophilization process. A key focus of this paper is the relevant measurement of surface area, with experimental data demonstrating the performance and value of novel instrumentation for in-situ characterization.