A reliable supply of life-saving drugs requires understanding and mitigating any variability to support consistent supplies. However, the crucial timelines for making a drug product available to patients can be heavily impacted when variability is introduced through raw materials such as cell culture media (CCM) and reagents.
Investigating a failure in production is costly and time-consuming and can delay product supply to the market – so a proactive risk-based approach is crucial to understand and mitigate the key factors that can introduce product variability.
The paper aims to drive regulatory bodies, drug manufacturers, supply partners, and N-1 suppliers toward a mutual understanding of the problem of trace element variation and the possible risk mitigation solutions.
Sources of impurity
Biopharmaceutical products have regulatory filings with specific medium formulations, but the challenge is to keep the products within specifications by minimizing overall variability, including elemental impurities. Though the impact of CCM variability can differ, manufacturers and supply partners must understand the sources of elemental impurities. Building bioprocesses to accommodate variability introduced by raw materials will therefore significantly benefit industry.
The paper can be used to overcome the challenge of raw material variability and help manufacturers work with CCM suppliers to collect data on each product lot for specific elements, which can be trended over time. Risk can also be partially mitigated by establishing quality programs with N-1 supply partners. However, this may be unfeasible for materials not used primarily by media manufacturers; these materials would need customized solutions and a proactive lot-screening approach before being used in manufacture.
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.
It is essential to continue efforts to understand the sources of variation and implement risk mitigation strategies. This is where the BioPhorum document can play a significant role. Though there may not be a single or ideal solution for this issue, BioPhorum’s rational approach can be used by all parties to understand the impact on their processes and products, to drive the identification of mitigation strategies.