It is important to continue efforts to understand the sources of trace element variation and implement risk mitigation strategies. End-to-end knowledge exchange, i.e., traceability of the individual components used in a manufacturing process all the way to its manufacturer, will create a reliable system to understand and troubleshoot any variability.
Building bioprocesses to accommodate variability introduced by raw materials would significantly benefit industry. It is well understood that current biopharmaceutical products have regulatory filings with specific medium formulations – the challenge is to keep the product within specifications by minimizing overall variability, including elemental impurities.
This paper aims to drive regulatory bodies, drug manufacturers, supply partners and N-1 suppliers toward a common understanding of the problem and possible risk mitigation solutions. Though there may not be a single or ideal solution for this issue, all parties can take a common rational approach to understand the impact on their processes and products, and drive the identification of mitigation strategies.
The paper includes an extensive case study that provides a real-life example of the importance of trace element control. It also discusses the supporting data on individual lots of raw materials that helped the team to understand the variability in N-1 raw materials and industry’s efforts for risk mitigation. Finally, the paper contains simple flow diagrams to help biopharmaceutical manufacturers and supply partners proactively manage risks associated with trace element variability.