RT Journal Article
SR Electronic
T1 Determining Maximum Allowable Rubber Stopper Displacement for Container Closure Integrity (CCI)
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 688
OP 692
DO 10.5731/pdajpst.2020.011726
VO 74
IS 6
A1 Lara Nonis
A1 Martin Vogt
A1 Susanne Joerg
A1 Hanns-Christian Mahler
A1 Franziska Riesen
A1 Gabriele Roidl
A1 Federico Sabini
A1 Roman Mathaes
YR 2020
UL http://journal.pda.org/content/74/6/688.abstract
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.