治疗用卡介苗（西林瓶装）质量属性、稳定性和相容性研究

Quality Attributes, Stability, and Compatibility of BCG for Therapeutic Use (Vial?Packaged)

关键词:  治疗用卡介苗  西林瓶  安瓿瓶  质量属性  稳定性  相容性

Key words:  BCG for therapeutic use  vial  ampoule  quality attributes  stability  compatibility

摘要:

目的 评价治疗用卡介苗由安瓿瓶更换为中硼硅玻璃管制注射剂瓶（棕色）与氯化丁基橡胶塞内包材后的质量属性、稳定性和相容性。方法 按《中国药典》（2020版）的方法对西林瓶装治疗用卡介苗进行检定，并增加制品密封性检查以及抑瘤试验（艾氏腹水瘤），比较西林瓶装与安瓿瓶装治疗用卡介苗关键质量指标，并对西林瓶包装系统开展迁移试验、内表面侵蚀性考察、加速模拟脱片试验及胶塞急性毒性检查。结果 西林瓶装治疗用卡介苗各质量属性及加速稳定性活菌数与安瓿瓶装治疗用卡介苗无显著差异（P > 0.05）;实时稳定性水分虽与安瓿瓶装治疗用卡介苗存在显著差异（P < 0.05），但不影响活菌数和浓度。不同储存温度和放置方式下西林瓶内表面均光滑平整，未见腐蚀、脱片及有害物质迁移；胶塞急性毒性检查合格。结论 西林瓶及胶塞组合可作为安瓿瓶的替代包装方式。

Abstract:

OBJECTIVE To evaluate the quality attributes, stability, and compatibility of BCG for therapeutic use following the replacement of ampoules with an inner packaging material combination consisting of medium borosilicate glass injection vials (amber) and chlorobutyl rubber stoppers. METHODS The vial packaged BCG for therapeutic use was tested according to the methods specified in the Chinese Pharmacopoeia (2020 edition), with additional tests including container-closure integrity testing and tumor inhibition test (Ehrlich''s ascites carcinoma). The critical quality attributes were compared between the vial-packaged and ampoule-packaged BCG for therapeutic use. In addition, migration studies, examination of inner surface corrosion, accelerated simulated delamination testing, and acute toxicity testing of the rubber stoppers were conducted on the vial packaging system.. RESULTS No significant differences (P > 0.05) were observed between the vial-packaged and ampoule-packaged BCG for therapeutic use in terms of the various quality attributes and viable count under accelerated stability. Although a significant difference (P < 0.05) was observed in moisture content under real-time stability between the two presentations, this difference did not affect the viable count or concentration. Under different storage temperatures and orientations, the inner surfaces of the vials remained smooth and intact, with no evidence of corrosion, delamination, or migration of harmful substances. The acute toxicity test of the rubber stoppers met the specified requirements. CONCLUSION The combination of vials and rubber stoppers can serve as an alternative packaging to ampoules.