Freeze drying--principles and practice for successful scale-up to manufacturing.

Freeze Drying involves transfer of heat and mass to and from the product under preparation, respectively, thus it is necessary to scale these transport phenomena appropriately from pilot plant to manufacturing-scale units to maintain product quality attributes. In this manuscript we describe the principal approach and tools utilized to successfully transfer the lyophilization process of a labile pharmaceutical product from pilot plant to manufacturing. Based on pilot plant data, the lyophilization cycle was tested during limited scale-up trials in manufacturing to identify parameter set-point values and test process parameter ranges. The limited data from manufacturing were then used in a single-vial mathematical model to determine manufacturing lyophilizer heat transfer coefficients, and subsequently evaluate the cycle robustness at scale-up operating conditions. The lyophilization cycle was then successfully demonstrated at target parameter set-point values.