Assessment of innate immune response modulating impurities in glucagon for injection.

Abstract

Glucagon for Injection is a polypeptide hormone medication used to treat patients with severe hypoglycemia or low blood sugar. Only recently, was a generic version of glucagon for injection approved by the FDA. While the generic version was deemed equivalent to its brand-name counterpart, the two glucagon products were produced using different manufacturing processes. The brand-name glucagon is produced via recombinant DNA while the generic glucagon is produced by peptide synthesis. Different manufacturing processes can result in different levels of innate immune response modulating impurities (IIRMIs). This study utilized a cell-based assay method, which allows for detection of a broad spectrum of impurities, to investigate the IIRMI risks of the generic glucagon to make sure it has similar or less immunogenicity risks than the brand-name glucagon product. Three commercial cell lines (RAW-Blue™, HEK-Blue™-hNOD1 and HEK-Blue™-hNOD2) carrying a secreted embryonic alkaline phosphatase reporter construct were used to quantify the level of innate immune responses after being treated with the glucagon drugs. The study results showed that despite differences in manufacturing process, the innate immunogenicity risk in the synthetic (generic) glucagon was at negligible level and comparable to the recombinant (brand-name) glucagon product.