Laboratory and Techniques
Biopharma Technology operates two laboratories dedicated to freeze drying. We use a range of equipment and analytical techniques to characterize products and monitor cycles to ensure that the development work we carry out is optimized.
Freeze Drying Microscopy
Freeze Drying Microscopy (FDM) is an established technique for analyzing formulations for freeze drying. The most important critical temperature for successful freeze drying, collapse temperature (Tc), can be identified quickly and easily. FDM can also be used to observe structural changes such as crystallization, the potential for skin / crust formation, and the effects of annealing. We use the Lyostat freeze drying microscope, which requires just 2 μl of product and around 20 minutes for a single analysis.
DTA & Impedance Analysis
Many formulations, particularly complex pharmaceutical or biotech compounds, contain a mixture of components with different crystallization behaviors. At low temperatures, such products can undergo invisible changes that have profound implications for their long-term stability. Impedance analysis can provide an indication of molecular mobility within a frozen sample, while DTA allows determination of significant endothermic or exothermic events such as glass transitions, crystallizations and eutectic melting. The use of DTA / Impedance Analysis in freeze drying was pioneered by Biopharma and Prof. Louis Rey, and this analysis is conducted on Biopharma’s Lyotherm instrument in our laboratories.
Karl Fischer Moisture Analysis
Accurately estimating the moisture in a freeze dried product is necessary for many reasons including process monitoring, cycle control, regulatory purposes and validation. Karl Fischer is a popular and widespread moisture determination method, which is highly accurate and can be run with small sample sizes. Moisture content will vary across each batch so it is typical to run several analyses to ascertain an average and range of results. This data is vital to prove that the product is being processed to acceptable parameters.
Differential Scanning Calorimetry
Differential scanning calorimetry (DSC) is a thermoanalytical technique used to detect physical transformations such as phase transitions. It can detect exothermic and endothermic events such as crystallization as well as more subtle events such as glass transitions. In freeze drying, DSC has many applications including determination of thermal characteristics, investigations into the effects of annealing on crystallization, and investigations of the lyophilized (dry) product’s properties in order to evaluate storage conditions—for example glass transitions and recrystallization of excipients.
Pilot-Scale Freeze Dryers
For conducting R&D or production work on a large range of products it is important to have flexibility in process capabilities. Our freeze dryers feature the type of controls and systems found on larger production systems but in lab-friendly footprints. Biopharma use a combination of research-scale and pilot-scale freeze dryers to allow us to process a range of batch sizes. The systems feature the same control system and designs so they can be used in combination or interchangeably. The software allows programming and storage of multiple multi-step freeze drying cycles, data monitoring and post-process evaluation. Our freeze dryers are a combination of “Genesis” and “Ultra” freeze dryers from SP Scientific.
Biopharma’s dedicated cytotoxic handling facility has been built to Class 7 standards and offers exemplary containment and safety features. The suite contains a full range of characterization and analysis equipment as well as a 0.56m2 pilot-scale freeze dryer. This enables us to provide product and process development services and small scale production runs.