Optimisation of biopharmaceutical buffer management to maximise the benefits of inline preparation systems

Buffer management is a significant challenge for biopharmaceutical manufacturing, accounting for a high proportion of the overall cost of manufacture and is frequently responsible for production bottlenecks. The industry trend towards greater adoption of inline buffer preparation systems has offered considerable improvements, however limited research has been undertaken to optimise implementation, which provides a barrier to maximising the potential of the technology. A detailed process model was used to evaluate the impact of key design variables on the overall cost of buffer supply, considering capital and operational costs. This was achieved by means of a non-replicated full factorial design composed of four variables: process requirements, stock solution concentration selection, operating shift pattern and the use of multi-batch preparation, comprising 1,200 experimental runs. While the adoption of inline buffer preparation is clearly beneficial, this study identified that the careful consideration of design and operating variables can substantially reduce the cost of buffer management even further with a mean cost reduction of 20 % from the best case compared to the worst across each process scenario. The proposed approach to optimise stock solution concentration selection has a demonstrable impact on the cost of manufacture. The outcome further identifies the important role of multi-batch preparation and the benefits of transitioning away from the traditional 24/7 buffer preparation operation. The results from this research establish a roadmap for optimisation of inline buffer preparation, identifying key design variables, which influence the cost of buffer, and provide a methodology for optimisation of stock solution concentration selection.