Amphastar Pharmaceuticals, Inc., Rancho Cucamonga, California, United States of America.
PLoS One. 2022 Nov 21;17(11):e0277922. doi: 10.1371/journal.pone.0277922. eCollection 2022.
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.
注射用胰高血糖素是一种多肽激素药物，用于治疗严重低血糖或低血糖的患者。直到最近，美国食品药品监督管理局才批准了一种注射用胰高血糖素的仿制药。虽然仿制药被认为与原研药等效，但这两种胰高血糖素产品的生产工艺不同。原研胰高血糖素是通过重组 DNA 生产的，而仿制药是通过肽合成生产的。不同的生产工艺可能会导致不同水平的固有免疫反应调节杂质（IIRMIs）。本研究利用基于细胞的检测方法，该方法可检测广泛的杂质，以调查仿制药胰高血糖素的 IIRMI 风险，以确保其免疫原性风险与原研药产品相似或更低。该研究使用了三种商业细胞系（RAW-Blue™、HEK-Blue™-hNOD1 和 HEK-Blue™-hNOD2），它们携带分泌型碱性磷酸酶报告基因构建体，用于在接受胰高血糖素药物治疗后定量固有免疫反应的水平。研究结果表明，尽管生产工艺不同，但合成（仿制药）胰高血糖素的固有免疫原性风险处于可忽略水平，与重组（原研药）胰高血糖素产品相当。
