Lyophilization cycle development, optimization and scale-up
For many labile (bio)pharmaceutical drugs, lyophilization is the method of choice to achieve a stable product. As lyophilization is an expensive process, it is of high importance to develop economical freeze-drying cycles suitable for larger-scale production of the product. At Coriolis Pharma we are highly experienced in the development, optimization, scale-up and transfer of lyophilization processes for (bio)pharmaceutical drugs. In combination with our experience in analytical and (formulation) development, a complete package can be offered to the customers.
For the lyophilization cycle development appropriate process parameters for the following steps are identified and optimized:
- freezing conditions: freezing rate, shelf temperature during freezing, duration of the freezing step and possible annealing steps
- primary and secondary drying conditions: shelf temperature, pressure, ramp from freezing step to primary drying step and from primary to secondary drying
- stoppering conditions: vacuum, type of gas used during stoppering
Coriolis Pharma is equipped with freeze-driers of various sizes and drying capacities, which allows us addressing not only freeze-drying cycle development in lab scale freeze-driers, but also scale-up questions already at an early stage. From the very beginning of process development we consider the suitability of the lyophilization cycle for a later scale up and transfer to the production facilities of our customer. Moreover, in close communication with the chosen CMO of our customer we can further assist on site to optimize and validate the lyophilization process towards economical cycle times and scale for the commercial product.
Freeze-drying processes are monitored by modern process analytical tools. Karl-Fischer titration (residual moisture), differential scanning calorimetry (liquid and dried state) and X-ray powder diffraction are routinely applied to guarantee a rational design of freeze-drying cycles. Moreover, it is possible to extract samples from the running processes by a sample thief or by individual shelf closure to perform in-process controls on the dried product or to generate products of varying residual moisture content in one cycle.
- Freeze-dryer, lab scale (Epsilon 2-6D, Martin Christ, 0.24 m² shelf area, 6 kg ice condenser capacity)
- 2 Freeze-dryer, pilot scale (Epsilon 2-12D special, Martin Christ, 1.0 m² shelf area; 12 kg ice condenser capacity, equipped with MKS/ Pirani, 12 thermocouples and individual shelf closure)
- Freeze-dryer, pilot scale (Lyostar III, FS Genevac, 0.54 m² shelf area, 16 kg ice condenser capacity, equipped with MKS/Pirani, 16 thermocouples and sample thief)
- Lab scale spray-driers (B-195 and B-290 Büchi)
- Inert spray-dryer for organic solvents (B-295 Büchi)
The service of Coriolis Pharma includes:
- development and optimization of lyophilization cycles
- scale-up of lyophilization cycles and assisting the transfer to the CMO
- physico-chemical characterization of dried products
- production of lyophilized material for pre-clinical studies under sterile conditions (non-GMP)
- production of lyophilized products differing in residual moisture