Experimental validation of multi-vial control for primary drying in a pilot-scale unit

Primary drying is the bottleneck of pharmaceutical lyophilization, as it represents the most time and energy-consuming stage and largely determines the quality of the final product. The common practice runs the process under pre-calculated input profiles while considering average drying dynamics for the batch. This results in conservative and un-derperforming cycles. In this regard, the paper proposes and experimentally validates an in-line control strategy for primary drying. It explicitly accounts for intra-lot drying het-erogeneity using three models, each one calibrated for a reference vial position in the chamber. Two separate experiments evaluate the proposed framework: offline and in-line process control. Validation on a pilot-scale unit shows a cycle time reduction of the proposed approaches compared to standard drying protocol at constant operating con-ditions. The input profiles obtained by offline control lead to a 16% shorter cycle time; however, the lack of feedback during the cycle impedes addressing potential parametric variations and model mismatches. Conversely, in-line control yields a reduction of 13% while allowing careful monitoring of the product status, ensuring a more dependable cycle. In both cases, the visual quality inspection confirms the acceptability of the final product without visible degradation.(c) 2023 Institution of Chemical Engineers. Published by Elsevier Ltd. All rights reserved.