Developing an Effective Lyophilization Cycle

The optimization of lyophilization process provides critical and scalable synergies between the research work in development lab and the product manufacturing on GMP operation line, ensuring project outcomes are high quality, repeatable, and on time. A contract manufacturing and development organization (CDMO) that specializes in lyophilization relies on freeze drying systems to:

De-risk the product development process by conducting experiments at an R&D scale using lyophilizer technology using a trial-and-error or QbD (quality-by-design) approach.

Understand the thermal and physical characteristics during the development of the lyophilization cycle or when optimizing a known lyophilization cycle. This is essential as no two products are alike. The process is product specific.

Study the thermal characteristics of the product and processes, with a particular focus on CPPs (critical process parameters), such as temperature and timing for freezing, annealing, primary drying, and secondary drying; pressure for primary drying, etc. This also helps to bridge the product's physical properties through the use of DSC (modulated Differential Scanning Calorimetry) and SEM (Scanning Electron Microscopy), such as glass transition temperature (Tg’), Crystallization temperature (Tc), and Eutectic Melt temperature (Te) in DSC, and critical temperature in Freeze drying SEM.

Evaluate chemical and stability characteristics, focusing on reconstitution time, moisture content, assay, degradation products or impurities among other critical quality attributes.

Verify parameters that were established during development, focusing on scalability during GMP manufacturing.

Aseptically fill into washed and depyrogenated vials, half stopper, and load them into the lyophilizer.

Cap and visually inspect lyophilized vials to evaluate cosmetic and critical defects. Vials that successfully pass inspection will proceed to the next stages, including analytical testing.

Lyophilization cycles can last from hours to several days. To ensure a robust cycle and design space that delivers product with acceptable quality profile in the most cost efficient manner, is most critical.