Freeze-dried biopharmaceutical formulations – University of Copenhagen


Freeze-dried biopharmaceutical formulations

Although freeze-drying is widely used in peptide and protein formulation, the interaction between various excipients and proteins is not fully understood. Our aim is to obtain a deeper understanding of the influence of various composition and process parameters on the solid state form of both the excipient and the macromolecule. This information is necessary for the implementation of the quality by design (QbD) principle, which can be expected to influence the way of pharmaceutical processing towards the development of more rational processes.

In order to gain insight in to the systems, various analytical techniques such as X-Ray powder diffraction, NIR and Raman spectroscopy are applied. Parameters are systematically investigated by Design of experiments (DoE) and large data sets are handled applying multivariate data analysis, such as principal component analysis (PCA). The transfer of process analytical technology (PAT) tools towards biopharmaceutical formulations is seen as key benefit for process and formulation optimization.

Recent projects investigated for example:

  • Influence of solid content, excipient composition and protein presence on mannitol polymorphism
  • Process simulation by in situ freeze-drying in X-Ray powder diffractometer
  • Establishment of well-plate freezing for high throughput screening of protein formulations
  • A systematic approach on the formation of mannitol hemihydrate during freeze-drying