A Stochastic Modelling Approach to Describe the Effect of Drying Heterogeneity in the Lyophilisation of Pharmaceutical Vaccines

In sterile drug product and vaccine manufacturing, reducing the duration of the primary drying stage of a lyophilisation cycle is pivotal to streamline process development and optimise commercial plant operation. Mathematical models can be used to assist this optimisation exercise. However, the models currently available in the literature usually neglect the effect of intra-lot drying heterogeneity in the optimization framework. In this study, we provide a description of drying heterogeneity using a deterministic model that mimics the behavior of a single vial, while treating the most impacting model parameter as a stochastic quantity. The novelty of the proposed approach lies in the description of drying heterogeneity using a single additional parameter, without further complicating the single-vial model structure. The prediction fidelity of the proposed model is assessed with experimental data obtained in an industrial equipment. Results show a robust prediction fidelity of the model in describing the effect of intra-lot drying heterogeneity on the process key performance indicators (KPIs).