Obtaining heat transfer coefficients (K) distribution directly from mass flow measurements during the sublimation step of freeze-drying.

The knowledge of heat transfer coefficients (K) and their distribution is a crucial element in the successful transfer of a freeze-drying process to a new piece of equipment. Nevertheless, the implementation of the classical ice sublimation method is resource consuming, particularly in the industrial context, which represents a significant barrier to its application. This paper demonstrates that the K distribution can be calculated from the measurement of mass flow during a freeze-drying operation by reversing the results of process simulation calculations.

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate.

The stability of live-attenuated viruses is very challenging due to thermal sensitivity; therefore, solid form is usually required (often freeze-dried products). Micropellet technology is a lyophilization technology that has the potential to provide greater flexibility in the presentation of a given vaccine particularly in multi-dose format or in combination of different vaccines. As a novel vaccine alternative process, this spray freeze-dried (SFD) micropellet technology was evaluated using as a model a yellow fever virus produced in Vero cells (vYF).

Quality by design: optimization of a freeze-drying cycle via design space in case of heterogeneous drying behavior and influence of the freezing protocol.

Purpose: This paper shows how to optimize the primary drying phase, for both product quality and drying time, of a parenteral formulation via design space.

Methods: A non-steady state model, parameterized with experimentally determined heat and mass transfer coefficients, is used to define the design space when the heat transfer coefficient varies with the position of the vial in the array. The calculations recognize both equipment and product constraints, and also take into account model parameter uncertainty.