Trace Element Variation For Chemically Defined Cell Culture Media

To enable a reliable supply of life-saving drugs requires understanding and mitigation of variability to support consistent supply. This is essential for manufacturers and supply partners. The crucial timelines for making a drug product (DP) 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, resulting in delays of product supply to the market.

A proactive risk-based approach to understanding key factors that can introduce product variability is necessary to avoid these delays. One such factor  identified is elemental impurity variability introduced by CCM. Though the impact of the variability will differ, it is important that both manufacturers and supply partners understand the sources of elemental impurities and perform risk assessments to identify mitigation strategies. Such assessments will allow an understanding of the level of risk, and what steps may be taken to dissipate it.

Manufacturers rely on their supply partners to understand the sources of impurities and the variability within them; in turn, supply partners rely on their suppliers (N-1 suppliers) of raw materials to provide information. An ideal scenario would be that all relevant information is available to make decisions and establish mitigation plans. A thorough process mapping to understand the sources of variability may not be practical, as the supplier of the raw material may rely on their suppliers to provide the starting material. Though not ideal, the supply chain is complex, and one individual raw material may have multiple supply parties (manufacturer (including manufacturing process), country distributors, local distributors, etc.).

This paper is an effort to drive regulatory bodies, drug manufacturers, supply partners and N-1 suppliers toward a common understanding of the problem and possible solutions that can be taken towards risk mitigation. Though there may not be a single or ideal solution for this issue, a common rational approach can be taken by all parties to understand the impact on their processes and products, to drive identification of mitigation strategies.

©BioPhorum Operations Group Ltd, March 2022
https://doi.org/10.46220/2021DS001