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目的通过稳定性实验研究重组肿瘤坏死因子相关凋亡诱导配体(rshTRAIL)突变体的贮藏条件与货架寿命期,为大规模生产过程质量风险控制提供评估依据。方法采用细胞毒磺基罗丹明B法(SRB)测定体外抑瘤活性IC50值和高效液相色谱法(HPLC)测定纯度。结果 rshTRAIL突变体原液于(-20±5)℃冷冻条件下放置12个月内产品质量稳定,制剂在长时间、大剂量的光照射下各指标无明显变化,其稀释配制实验、在(25±2)℃下6个月的加速实验以及(5±3)℃长期实验12个月显示各项指标均符合要求,但应尽量避免在生产过程中长时间暴露在较高的环境温度与强光照射下,以降低蛋白在高温、强光下聚合带来的潜在风险。结论 rshTRAIL突变体制剂产品具有较好的稳定性,制剂配方对产品有很好的保护作用,根据ICH该产品的货架期可暂定为两年。
Objective To investigate the storage conditions and shelf life of recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rshTRAIL) mutant by stability experiment, and provide the basis for quality risk control of mass production. Methods The IC50 value of anti-tumor activity in vitro was determined by cytosolic sulfo-rhodamine B (SRB) assay and the purity was determined by high performance liquid chromatography (HPLC). Results The product quality of rshTRAIL mutants was stable within (-20 ± 5) ℃ for 12 months after being placed in the freezer. The dosage of rshTRAIL mutants did not change significantly under long-term and high-dose light irradiation. ± 2) ℃ 6 months accelerated test and (5 ± 3) ℃ 12 months long-term experiment showed that the indicators are in line with the requirements, but should be avoided in the production process for a long time exposed to higher ambient temperature and strong Light irradiation, in order to reduce the potential risk of protein polymerization at high temperature and high light. Conclusion The rshTRAIL mutant product has good stability. The formulation of the product has a good protective effect on the product. According to the ICH, the shelf life of the product can be tentatively scheduled for two years.