Process Model for Enhancing Yield in Sterile Drug Product Manufacturing

We present a process model for enhancing the yield in the manufacturing of sterile drug products, such as injectables, eye drops, or intravenous bags. The process typically consists of compounding, filtration, filling, and visual inspection and involves raw materials of active pharmaceutical ingredients, water for injection, excipients, and packaging materials. To define the process mathematically, we adopted the processing matrix, an approach for continuous chemical processes that enables consideration of all materials with guaranteeing mass balance. The vector- and matrix-based model was extended to describe the defect generation in the process that leads to loss of materials, such as defective products. We also defined a path flow diagram that visualizes the defect generation paths as an aid to identify relevant root causes. The model was applied in a case study of an intravenous bag manufacturing process and produced a promising idea for reducing the financially most critical defective product. Fault tree analysis was applied to reduce the number of paths, and relevant root causes could be identified in the filling operation and in the raw material. The developed model can serve as the basis that would replace the case-by-case approach of process improvement often observed in the industry.