Physical
Sciences Inc., in collaboration with the University of Connecticut, the
University of Massachusetts Lowell, Purdue University, Genentech and Merck, has
developed software modeling tools for lyophilization primary drying process
development and scale-up. The user-friendly software incorporates a heat and
mass transfer model of freeze-drying developed by Pikal et al. that includes
the effects of statistical variation and heterogeneous drying, distinguishing
sublimation from center, inner-edge and outer edge vials. Model validation
experiments were performed on two industry-supplied drug formulations to test
the ability of the new tool to develop primary drying cycles and correctly
predict product temperatures and drying times. Results from these experiments demonstrated
the predictive capability of the model, but highlighted the need to provide
accurate model inputs for process parameters. The use of the process
development and scale-up software model enables more rapid development of
freeze-drying processes, and provides process knowledge and design spaces that
support the development of optimized drying cycles.
This work was performed under a
Project Award Agreement from the National Institute for Innovation in
Manufacturing Biopharmaceuticals (NIIMBL) and financial assistance award
70NANB17H002 from the U.S. Department of Commerce, National Institute of
Standards and Technology.