Improving the sustainability of biopharmaceutical downstream processing through buffer recycling.

The production of biopharmaceuticals is a chemical- and water-intensive process. The consumption of water and chemicals is partly due to the need for many different buffers in large volumes during the downstream process, typically consisting of several chromatography steps. Given the global commitment to the goals for sustainable development and the anticipated growth of the biopharmaceutical market, the consumption of large buffer volumes is expected to become problematic. To address this, we propose the introduction of buffer recycling to reduce the consumption of water and chemicals. For solvent based pharmaceutical processes, solvent recycling through re-distillation is already established, but for water-based processes, this concept is still rather unexplored. In this study, buffer recycling was implemented during the equilibration phase of Protein A chromatography for antibody purification. We have investigated the potential gains of buffer recycling and demonstrated buffer recycling in two technical implementations: buffer recycling in a batch-to-batch process and buffer recycling in a multi-column process. Buffer recycling consists of buffer recovery and buffer reuse. During recovery, buffer that has been used during equilibration is collected and pH adjusted, and during the reuse step, the recovered buffer is reintroduced into the process. By introducing buffer recycling, we could reduce the equilibration buffer consumption by almost 50 % in this phase, corresponding to more than 10 % of the total buffer use in the Protein A protocol, and have seen no changes in antibody yield or purity. Hence, through buffer recycling, we can improve the sustainability in biomanufacturing by using less water and chemicals.