Research and Development, Lupin Limited (Biotechnology Division), Pune, Maharashtra, India.
PLoS One. 2023 Aug 9;18(8):e0289745. doi: 10.1371/journal.pone.0289745. eCollection 2023.
Pegfilgrastim is administered as an adjunct to chemotherapy to reduce the incidence of febrile neutropenia and associated infectious complications. Lupin's Pegfilgrastim is a proposed biosimilar to the U.S.-referenced Neulasta®. Demonstration of biosimilarity requires extensive physicochemical and functional characterization of the biosimilar, and demonstration of analytical similarity to the reference product, in addition to clinical studies. This work is a case study for demonstrating the analytical similarity of Armlupeg (Lupin's Pegfilgrastim) to Neulasta® with respect to structural and physicochemical attributes using several robust, orthogonal, and state-of-the-art techniques including high-end liquid chromatography, mass spectrometry, and spectroscopy techniques; circular dichroism; differential scanning calorimetry; nuclear magnetic resonance; analytical ultracentrifugation; and micro-flow imaging. Functional similarity was demonstrated using an in vitro cell proliferation assay to measure relative potency and surface plasmon resonance to measure receptor binding kinetics. Furthermore, comparative forced-degradation studies were performed to study the degradation of the products under stress conditions. The product attributes were ranked based on a critical quality attributes risk score according to their potential clinical impact. Based on criticality, all analyses were statistically evaluated to conclude analytical similarity. Lupin's Pegfilgrastim was comparable to Neulasta® as demonstrated via structural, functional, and purity analyses. Lupin's Pegfilgrastim complied with the quality and statistical ranges established using Neulasta®. Both products follow the same degradation pathways under stress conditions as observed in the forced-degradation studies. No new impurity or degradation product was observed in Lupin's Pegfilgrastim. These data conclusively demonstrate the analytical similarity of Lupin's Pegfilgrastim and Neulasta®.
培非格司亭与化疗联合使用，可降低发热性中性粒细胞减少症及相关感染并发症的发生率。鲁宾的培非格司亭是一种与美国参考药物 Neulasta®类似的生物类似药。生物类似药的相似性需要对生物类似药进行广泛的理化和功能特征分析，并证明与参比产品具有分析相似性，此外还需要进行临床研究。这项工作是一个案例研究，旨在使用几种强大、正交和最先进的技术（包括高效液相色谱、质谱和光谱技术、圆二色性、差示扫描量热法、核磁共振、分析超速离心和微流成像）来证明 Armlupeg（鲁宾的培非格司亭）与 Neulasta®在结构和理化属性方面的分析相似性。通过体外细胞增殖测定来测量相对效力，通过表面等离子共振来测量受体结合动力学，从而证明了功能相似性。此外，还进行了比较强制降解研究，以研究产品在应激条件下的降解情况。根据对临床的潜在影响，根据关键质量属性风险评分对产品属性进行了排名。根据关键性，对所有分析进行了统计评估，以得出分析相似性的结论。鲁宾的培非格司亭与 Neulasta®通过结构、功能和纯度分析具有可比性。鲁宾的培非格司亭符合使用 Neulasta®建立的质量和统计范围。在强制降解研究中观察到，两种产品在应激条件下都遵循相同的降解途径。在鲁宾的培非格司亭中未观察到新的杂质或降解产物。这些数据最终证明了鲁宾的培非格司亭与 Neulasta®的分析相似性。
