Process control and design of drying technologies for biopharmaceuticals – A review

Abstract

Research into the production of solid-state biomolecules has increased in the last decade, uncovering new routes of administration and enhanced product stability. Freeze drying is the most common industrial method for biomolecule dehydration, however it requires long processing times and does not allow for particle engineering. Hence, new drying techniques are constantly being developed to produce dried biopharmaceuticals, facilitating the switch from batch to continuous manufacturing and improving control over particle attributes. The sensitive nature of biological products requires comprehensive optimisation of these new methods against the various degradative stresses imposed by drying. Process control and optimisation is key in minimizing many of these stresses, allowing production of dried powders with pre-determined characteristics (e.g. particle morphology, size and density). In this review, we provide a detailed overview of current methods used to date for the drying of biologics and the particle engineering capabilities of these methods, along with the process control possibilities that emerge with process analytical technology (PAT). We also look at the extent of mass and energy balances informing process optimisation and the effect of process controls on biomolecule stability, drying efficiency, and particle engineering.