Research area: Freeze-Drying Biologics

Research sponsor: ESPRC Imperial/UCL and NIBSC

Project overview

Fundamentals of the Stability of Freeze Dried Biologics

Freeze drying is gaining in importance as the number of biopharmaceuticals that are unstable in a solution increases. The technique offers the opportunity to gently dry temperature-sensitive drugs such as proteins or peptides. Most biologics are inherently unstable in the liquid state yet of the 15 top selling pharmaceuticals in 2013, 6 were biologics and 4 of the 6 were freeze dried, wherein freeze drying results in amorphous liquid like material state. Current trends show that the number of biologic, and thus freeze-dried products will see growth of 10% in the next 10 years. So a better understanding of the interaction between residual water and the stability of lyophilised materials is critical to delivery of more stable biological medicines.

The project will investigate the relationship between residual moisture content, the structure of freeze dried material and the stability of biologics in the freeze dried state. Using advanced methods for freeze dried product characterisation at both Imperial College as well as NIBSC, this project will exploit the NIBSC’s unique access to a wide range of biologic materials for this investigation of freeze dried biologics. The outcome of this work will be directly translatable into the ongoing work of the NIBSC as well as commercial biologics production. We aim to establish using a range of industrially relevant freeze dried biologics supplied and produced by NIBSC what is the optimum moisture content in the freeze dried product which delivers best final product stability. Such an insight will cut across our core understanding of how to optimise the stability of any freeze dried biologic materials, and provide direct industrially usable understanding.

References:
1. Devi S and Williams DR, “Morphological and compressional mechanical properties of freeze-dried mannitol, sucrose and trehalose cakes”, Journal of Pharmaceutical Sciences (2013), 102, 4246-4255.
2. R. Ho and J. Y. Y. Heng, “A Review of Inverse Cas Chromatography and its development as a tool to characterize anisotropic surface properties of pharmaceutical solids”, KONA Powder and Particle Journal (2013), 30, 164-180.
3. Tang, X. and Pikal, M.J.,“ Design of freeze-drying processes for pharmaceuticals: practical advice”, Res (2014), 21(2), 191-200.
4. Devi S and Williams DR, “ Density dependent mechanical properties and structures of a freeze dried biopharmaceutical excipient - sucrose”, European Journal of Pharmaceutics & Biopharmaceutics (2014), 88, 939-6411.