Demonstrating Intactness of Biopharmaceutical Products: Intact Molecular-Weight Analysis and Terminal Sequencing of Proteins

摘要

Regulations require that biomanufacturers assess the intactness of protein and glycoprotein products as well as confirm the terminal sequences to look for existing variations. ICH Q6B guideline section 6.1.1 c statesTerminal amino acid analysis is performed to identify the nature and homogeneity of the amino- and carboxy-terminal amino acids. If the desired product is found to be heterogeneous with respect to the terminal amino acids, the relative amounts of the variant forms should be determined using an appropriate analytical procedure. The sequence of these terminal amino acids should be compared with the terminal amino acid sequence deduced from the gene sequence of the desired product.