Seemingly Endless Biomolecular Structural Variants

• Published in: The Challenge of CMC Regulatory Compliance for Biopharmaceuticals pp. 381 - 406
• Main Author: Geigert, John
• Format: Book Chapter
• Language: English
• Published: Switzerland Springer 2023; Springer Nature Switzerland
• Subjects: Aggregation; Biomolecular; Capsids; Deamidation; Empty; Genomic; Glycosylation; Oxidation; Posttranslational; Primary; Proteomic; Secondary; Structure; Tertiary; Truncation
• ISBN: 3031319087; 9783031319082
• DOI: 10.1007/978-3-031-31909-9_11

Compared to chemical drugs, biopharmaceuticals have a highly complex, seemingly endless, biomolecular structural variant profile, especially due to the biological cell-based manufacturing processes employed in their biosynthesis. And each type of biopharmaceutical – be it a protein, a viral vector or a genetically modified patient cell – will have not only multiple structural variants but also different types of structural variants. Sometimes a molecular structural variant will have the same activity, safety and efficacy as the intended biopharmaceutical, but sometimes not. Therefore, knowing the type of biomolecular structural variants that could be present, and how the manufacturing process contributes to their presence, are important first steps in a patient safety risk assessment. In this chapter, the numerous biomolecular structural variants associated with four different biopharmaceutical types (recombinant proteins and monoclonal antibodies, viral vectors, genetically modified patient cells, mRNA non-viral vectors), will be examined. Application of the minimum CMC regulatory compliance continuum risk-based approach towards the level of understanding expected for the biomolecular structural variants will be discussed.