技术共探丨注射剂配伍微生物挑战稳定性研究

监管机构

法规/指导原则

核心要求

NMPA

《中国药典》四部通则 “9001原料药物与制剂稳定性试验指导原则”

应对配制或稀释后使用、在特殊环境（如高原低压、海洋高盐雾等）使用的制剂开展相应的稳定性研究，同时还应对药物的配伍稳定性进行研究，为说明书/标签上的配制、贮藏条件和配伍或稀释后的使用期限提供依据。

CDE

《化学药品注射剂配伍稳定性药学研究技术指导原则（试行）》

当配伍后药液需在2-8℃下保存超过24小时或25℃/30℃保存超过4小时，建议参照相关要求进行微生物挑战试验，微生物增长应不超过0.5lg值。配伍稳定性考察时间应不短于拟定说明书中的允许时限。

FDA

Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act

To support an in-use expiration date that exceeds 4 hours at room temperature (or longer hold under refrigerated conditions), an outsourcing facility should conduct appropriate microbial challenge studies (in-use stability microbiological testing). These challenge studies are designed to simulate clinical conditions of admixture and hold, using the actual formulation, container/closure system, and proposed hold time/temperature conditions intended for clinical use.

EMA

Note for Guidance on Maximum Shelf-Life for Sterile Products for Human Use after First Opening or Following Reconstitution

If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution / dilution (etc) has taken place in controlled and validated aseptic conditions.