S26: Integration of the Upstream and Downstream Process Development - the Key to Develop a Robust Downstream Process Ready for Technology Transfer and Manufacturing

Downstream process is commonly affected by multiple factors with the upstream process robustness and scale-up being a major one. In most cases the downstream PD starts well before the upstream process is developed/locked, therefore the risk of the downstream process not behaving as expected is usually high and often seen in the early steps of the downstream process. This risk can be significantly mitigated by integration of the upstream and downstream in downstream PD plan. In this presentation, several detailed case studies will be discussed to exemplify the impact of the upstream process change and instrument change on downstream process such as inclusion body preparation, refolding, post-refolding clarification and capture column steps. Data generated at both PD and manufacturing scales will be compared and discussed to conclude that a well-designed downstream PD plan can accommodate a lot of the potential variables in order to develop a reasonably robust downstream process.