In continuous pharmaceutical manufacturing, the degree of back-mixing has two contrary effects on the propagation of disturbances through a process. Firstly, back-mixing results in the contamination of adjacent material by strong disturbances and additional losses. However, the available measuring frequency in the process must detect all disturbances causing OOS material. Consequently, back-mixing must also smoothen out all undetectable disturbances. Therefore, we introduce the minimal needed measuring frequency and the mean loss in yield as indicators for the degree of back-mixing. In a case study, we utilize a dry granulation line from the literature and those indicators to discuss a strategy for the usage of multiple diversion points, the impact of uncertainties in measuring the degree of back-mixing, and setting operational parameters in the tablet press. This way, we reveal opportunities for reducing discharged material due to back-mixed disturbances in a continuous manufacturing line. (C) 2021 Elsevier Ltd. All rights reserved.

• Technical University of Dortmund
• Invite GmbH

• Oral solid dose
• Process characterization

1. Back-mixing
2. Dry granulation
3. oral solid dose
4. Process characterization
5. Research Article