Analytical assessment of safety and efficacy of filgrastim and pegfilgrastim formulations for treatment of chemotherapy-induced neutropenia

对非格司亭和培非格司亭制剂治疗化疗引起的嗜中性粒细胞减少症的安全性和有效性进行分析评估

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Abstract

A recombinant preparation of human granulocyte-colony stimulating factors (rh-GCSF), filgrastim and its advanced form pegfilgrastim i.e., pegylated form have widely been employed in the management of neutropenia caused by cancer chemotherapy. Their formulations from different manufacturers are commercially available in the market for patient use. Though regulatory guidelines worldwide have laid down methodology for ensuring quality control testing of such products before entering into the market, yet, the quality data of copy products are seldom available. In this 8 year retrospective analysis carried out on seven products each of both the molecules, a comparison of quality parameters based on their safety and efficacy studies is presented to understand any variability. The utilization of orthogonal techniques was done for the filgrastim and pegfilgrastim products of different manufacturers to address the critical quality attributes for identity, purity, potency and bioactivity. The quality of the batches was analyzed based on compendial guidelines for filgrastim products and manufacturers' method of analysis for pegfilgrastim products. The products were evaluated for presence of endotoxin, aggregate impurities (monomer > 97%), related proteins (< 3.5%), and other impurities with different molecular masses (no separate band in SDS-PAGE) and were found within limits. The products were also assessed for their potency though cell-based proliferation assay (80-125%) and protein content (80-125%). They were found to be of standard quality with no substantial differences in quality parameters among batches of a product (intra-variability) and among all different products (intervariability).

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