Pharmaceutical container/closure integrity. V: An evaluation of the WILCO "LFC" method for leak testing pharmaceutical glass-stoppered vials.
The sensitivity, reliability, reproducibility and ease of use of the WILCO LFC package integrity test method was evaluated by preparing and testing a series of rubber-stoppered glass vials which were modified by affixing a glass micropipette through the vial side wall. The test units contained water, 50% aqueous ethanol, 20% lithium chloride or 20% aqueous glycerol. Leakage measurement obtained by LFC testing were compared to helium leak rate measurements. The LFC methods detected all leak > 0.0014 standard cubic centimeters per second (sccs), which represents a sensitivity about fourteen-fold greater than standard vacuum decay methods. The minimum detectable leak corresponded to a nominal micropipette internal diameter of between 1 and 2 microns. The effective detection range corresponded to a leak size associated with a 40 to 100% probability of microbial ingress based on a previously reported logistical regression model between helium leak rate and microbial immersion. The sensitivity did not vary with solvent or testing duration in range of 5 to 10 seconds. The coefficient of variation was about 3%. The LFC operation was rapid and without apparent mechanical or electronic problems over the two day testing period used in these studies.
Kirsch
L E
LE
Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, USA.
Nguyen
L
L
Kirsch
A M
AM
Schmitt
G
G
Koch
M
M
Wertli
T
T
Lehmann
M
M
Schramm
G
G
D004349:Drug Packaging / Q000592:standards*; D005898:Glass; D006371:Helium / Q000032:analysis
D006371:Helium