RT Journal Article
SR Electronic
T1 Air-water binary gas integrity test for sterilizing and virus filters
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP pdajpst.2016.006437
DO 10.5731/pdajpst.2016.006437
A1 Giglia, Sal
A1 Caulmare, John
A1 Nhiem, David
A1 Porreca, David
YR 2016
UL http://journal.pda.org/content/early/2016/10/21/pdajpst.2016.006437.abstract
AB Reliability of retention performance is of paramount importance for membrane filters designed for sterile and virus filtration. To achieve dependable retention, an integrity test can be applied to ensure the absence of oversize pores or defects that can compromise the retention capability of the filter. Probably the most commonly applied non-destructive integrity test for membrane filters is the gas-liquid diffusion test, with air and water often used as the gas-liquid pair. However, the sensitivity of the air-water diffusion test is limited by the fact that the diffusive flow rate for an integral membrane can span a range that is large compared to the flow contributed by a defect. A novel non-destructive air-water integrity test for microporous and nanoporous membranes is introduced here that provides improved test sensitivity by measuring the gas composition in addition to gas flow rate. Oxygen permeates through water faster than nitrogen, so with air as the challenge gas and water as the wetting fluid, the permeate stream will be enriched in oxygen. The permeate oxygen concentration is predictable, accurately measurable, and within a narrow and repeatable range for an integral membrane. A leak through the membrane will result in a deviation from the integral permeate concentration, signaling a defect. Compared to the conventional air-water diffusion test, this air binary gas (i.e., O2 and N2) test in which the permeate gas composition is measured (in addition to the diffusive flow rate) has a superior signal-to-noise ratio and was demonstrated to provide a significantly higher level of retention assurance for both sterilizing grade and virus filters. Since air and water are used as the gas-liquid pair, the air binary gas test also maintains the convenience, safety, and environmentally friendly aspects of the air-water diffusion test.