PT  - JOURNAL ARTICLE
AU  - Nonis, Lara
AU  - Vogt, Martin
AU  - Joerg, Susanne
AU  - Mahler, Hanns-Christian
AU  - Riesen, Franziska
AU  - Roidl, Gabriele
AU  - Sabini, Federico
AU  - Mathaes, Roman
TI  - Determining Maximum Allowable Rubber Stopper Displacement for Container Closure Integrity (CCI)
AID  - 10.5731/pdajpst.2020.011726
DP  - 2020 Nov 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 688--692
VI  - 74
IP  - 6
4099  - http://journal.pda.org/content/74/6/688.short
4100  - http://journal.pda.org/content/74/6/688.full
SO  - PDA J Pharm Sci Technol2020 Nov 01; 74
AB  - Sterile pharmaceuticals require they be developed and manufactured using suitable container closure systems to maintain sterility until product opening. Characterizing container closure integrity (CCI) in relation to rubber stopper displacement was controversially discussed during the Annex 1 revision process. An automated inspection system can reject units with displaced rubber stoppers, and the related acceptance criteria for such in-process testing can be established by adequate studies. In this manuscript, we describe a novel helium leak CCI testing method to study the relation of rubber stopper displacement and CCI. Ten different commonly used vial–rubber stopper combinations were characterized, which led to robust test results. Pronounced differences between the different vial–rubber stopper combinations were observed, clearly showing that the combination of different stoppers, vials, and caps led to significant differences in allowable stopper displacement for routine manufacture.