An NMR-Based Similarity Metric for Higher Order Structure Quality Assessment Among U.S. Marketed Insulin Therapeutics.

ABSTRACT: Protein or peptide higher order structure (HOS) is a quality attribute that could affect therapeutic efficacy and safety. Where appropriate, the HOS similarity between a proposed follow-on product and the reference listed drug should be demonstrated during regulatory assessment. Establishing quantitative HOS similarity for 2 drug substances, manufactured by different processes, has been challenging. Herein, HOS differences among U.S. marketed insulin drug products (DPs) were quantified using nuclear magnetic resonance spectra and principal component analysis (PCA). Then, the unitless Mahalanobis distance (D_M) in PCA space was calculated between insulin analog reference listed drugs and their recently approved follow-on products, and all D_M values were 3.29 or less. By

SUBMITTER: Wang D 

PROVIDER: S-EPMC12486139 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature