ABSTRACT
A one-year study to establish the container closure integrity (CCI) performance landscape of systems comprising rubber stoppers and glass vials was performed. Focus was on addressing the issues of CCI performance versus: (a) time, (b) compression levels and residual seal force (RSF) values, and (c) potential variation in results based upon the deterministic measurement method (tracer gas and frequency modulated spectroscopy). To reduce sample size to a manageable number, the study was based upon a design of experiments that considered a range of: (a) stopper formulations, sizes, and configurations; (b) vial sizes, types, and suppliers; and (c) compression levels. All systems showed good performance; there was no decrease in CCI with time, highlighting the general robustness of rubber-glass vial systems. Lower compression/RSF values tended to give slightly lower performance and wider scatter in data and thus should not be recommended for commercial applications. A small amount of oxygen exchange through the stoppers was observed for all systems-to be expected because rubber is known to be gas permeable. Consistent with models, RSF values decreased initially and then remained constant. Results are consistent with the literature.
Subject(s)
Drug Packaging/standards , Equipment Design/standards , Glass/standards , Rubber/standards , Technology, Pharmaceutical/standards , Drug Contamination/prevention & control , Drug Packaging/methods , Equipment Design/methods , Technology, Pharmaceutical/methods , Time FactorsABSTRACT
The U.S. Food and Drug Administration regulates outsourcing facilities with the same stringency they apply towards drug manufacturers. This means that outsourcing facilities, who must navigate the changing regulatory landscape to achieve and maintain 503B status, need to focus on qualifying container closure systems for their intended use. Container closure systems must be fit-for-purpose (i.e., suitable for in-use conditions relative to drug product stability over intended shelf-life and storage conditions). This article, the first of a two-part series, addresses the critical aspect of how to qualify systems for intended use regarding container closure integrity. The second part will address component selection.
