Complex Process-Related Impurity Profiles

Every manufactured human medicine contains residual impurities associated with its manufacturing process. Patient safety risk associated with the process-related impurities needs to be assessed. Compared to chemical drugs, biopharmaceuticals (whether recombinant proteins, monoclonal antibodies, viral vectors, genetically modified patient cells, or mRNA non-viral vectors) have a highly complex process-related impurity safety profile due to the biological manufacturing processes employed. In this chapter, the risk-based control strategy for prioritizing the concerns associated with the numerous process-related impurities produced by the different biopharmaceutical manufacturing processes, will be discussed. Application of the minimum CMC regulatory compliance continuum risk-based approach will be examined. In addition, four specific process-related impurities will be discussed in detailed – residual DNA, residual host cell proteins, endotoxin, and leachables.