Advancing Alternative Testing Methods
Advanced Test Concepts Inc. (ATC; Indianapolis) has developed advanced methods for testing container/closure integrity using mass extraction technology. The company markets the Intelligent Gas Leak Sensor (IGLS) to detect defects down to 2 microns in dry-goods packaging such as bottles, blister packs, and sterile trays; it offers the Intelligent Molecular Flow Sensor (IMFS) for detecting submicron defects in liquid-goods packaging such as sterile parenteral glass vials and syringes for injectable drugs.
“Ever since FDA drafted guidance for industry on the use of container closure system integrity testing in lieu of sterility testing back in 1998, we’ve been looking at alternative methods,” reports Hemi Sagi, ATC’s director. “The agency’s guidance was finalized in February 2008.”
The nondestructive systems employ patented microflow sensors to measure movement of total air, not just a specific gas, through packaging held under a hard vacuum within a testing chamber. “Microflow is a flow regime in which molecular effects have significant influence on flow rate and behavior,” explains Sagi. “We can correlate the flow rate of air in micrograms per minute through a package with a particular defect size. We have found the system to be more sensitive than the common dye ingress test method and with similar sensitivity to helium (tracer gas) test methods; it is not destructive like those requiring helium-filled test subjects or dye ingress tests.”
The nondestructive nature of the systems intrigues makers of expensive biological or combination products, says Sagi. “Companies prefer not to waste such products during testing, while enjoying a reliable and operator independent test method.”
They can be used for 100% inspection, which the EU Guidelines (EMEA) have come to favor for sterile glass and plastic ampules, given Annex 1 of the guideline. “Ampules are becoming less popular, however,” Sagi says. “But 100% inspection could be considered for a range of packages. Some packaging professionals believe that if you control packaging processes tightly, 100% inspection isn’t needed. But we sense that FDA leaning toward 100% inspection. The agency is concerned about consistent defects and random defects, and process control won’t catch random defects.”
The IGLS and IMFS sensor systems have been employed during stability testing as well as R&D for package development and process quality control (sampling), but Sagi believes they could one day replace the more commonly used integrity tests for routine testing of marketed products. ATC offers models VE and VE2 with the IGLS, and model ME2 with the IMFS.
These models could replace dye tests, tracer gas or vacuum decay test methods, says Sagi, crediting their greater sensitivity. “Ever since Michigan State University’s School of Packaging began studying allowable defect sizes, our concept has been to focus on getting down to 1-2 micron defects for sterile products.”
ATC is at that level for some packages, and getting closer with others. Sterile liquids in rigid packages, such as glass, can be inspected for submicron-sized defects using IMFS-based systems.
For medical devices packaged in nonporous packages such as flexible pouches and rigid trays, the IGLS-based systems can detect defects measuring 2 and 5 microns, to protect moisture-sensitive products, reports Sagi.
Defects in packaging with any sort of porous component, such as Tyvek, however, can only be detected at 50 microns and larger, which is two times better than the requirements of ASTM F2338-09, he explains. “It is hard to isolate whether the leak flow is from many torturous porous paths or a few large defects,” says Sagi.
In addition to selling models VE, VE2, and Me2, ATC also offers A2LA accredited IQ/OQ and will also employ the systems for validation and testing programs on a contract basis in its ISO 17025 accredited lab.