Evaluation of the Impact of Buffer Management Strategies on Biopharmaceutical Manufacturing Process Mass Intensity

Abstract

There is an increasing demand to improve the overall sustainability of the biopharmaceutical industry. A barrier to improvement has been the limited research undertaken in the area of environmental impact of key design decisions. The aim of this study was to perform a comprehensive evaluation of the impact of buffer management strategy and technology selection on overall process efficiency using process mass intensity (PMI) as a metric for comparison. The environmental impact of buffer management has yet to be fully understood, despite buffers being one of the most resource-intensive aspects of biopharmaceutical manufacturing. A detailed process model was used to evaluate the impact of buffer management on a monoclonal antibody (MAB) process at the 2000 L scale. This was achieved by means of a non-replicated full factorial design composed of six variables: product titre, quantity of unique buffers, preparation frequency, single-use threshold and equipment cleaning duration with two levels and buffer preparation strategy type with four levels. The study identified that buffer management has a critical impact on overall process mass intensity, demonstrating a possibility to achieve a reduction in PMI of up to 90% for the best scenario compared to the worst. The findings also indicated that single-use systems are greatly superior to stainless-steel systems in terms of overall process efficiency, which is consistent with established thinking. The results from this research represent a further significant step towards achieving a more sustainable biopharmaceutical industry, establishing buffer management as a critical focus area, quantifying the influence of key variables on process mass intensity and highlighting the benefits of using a process mass intensity metric as part of routine biopharmaceutical design.