How to Ensure Integrity and Sterility of Single-Use Assemblies for Manufacturings


Single-use systems have many clear advantages, however, one challenge is ensuring the integrity of these plastic bags and components. Microscopic breaches of integrity, even those that cannot be seen, can allow microbial ingress. Possible breaches extend beyond just the bags, so the entire single-use assembly including tubing, connectors, seals, etc. must be tested for integrity to ensure against potential contamination problems.

To address integrity concerns, companies that manufacture single-use components will typically conduct a visual inspection and perform pressure decay testing. Pressure decay testing is the industry standard for validating single-use bag integrity, however, there are limitations to the level of assurance this testing can provide.

ATMI’s HIT™ system addresses both the challenge of testing complete single-use assemblies and ensuring bag integrity at point-of-use. The system was first launched in 2010 as an in-house add-on testing service for the company’s 2-D bioprocess bags and manifolds, and now the HIT system has evolved to the next level. It is offered in multiple formats: either as add-on testing for the full line of ATMI 2-D and 3-D vessels up to 200L, or as a point-of-use-system to customers for implementation in their own facilities.

Question 1

Which components of the assembly do you recommend testing for any tears or problems?

All components are equally important when it comes to leaks. It is important to test each component and that is one benefit of the Helium Integrity Test. The entire assembly can be tested at one time to a very high level of accuracy.

Question 2

If you want to use this at your facility to test single use systems on site, how easy is it to use? How much training is required?

The Point-Of-Use variant of ATMI’s HIT system has been designed with ease of use foremost in mind. Before first use (i.e. during startup), and periodically thereafter, the system does have to be configured for the specific single-use assembly in question by an ATMI technician (a somewhat advance process involving recipe optimization and detector calibration). Once configured, operation from the end-user perspective is straight-forward; the user interface is strauight-forward, with a simple “start” button on the touch screen and a clear pass/fail indication at the conclusion of the test. The system software features multiple, password-controlled access levels to prevent unauthorized personnel from accessing the more complex (calibration, service and diagnostic) functionality. ATMI would provide annual calibration service as well as determination of minimal detectable defect size for particular single use assembly.
Prospective customers are encouraged to visit ATMI for a hands-on demonstration of the HIT system, and assess for themselves how it can fit into their process operations.

Question 3

Down to what level of contamination are you able to test?

The HIT™ System tests for defects in single-use assemblies which could potentially lead to contamination. The HIT™ System uses a control unit that houses highly-sensitive mass spectrometry equipment, and a test chamber with a fully customizable containment rack. The single use assembly to be tested is put into the test chamber and connected to service hoses, and then the test chamber is evacuated. During chamber evacuation, the test unit is pressurized with the helium gas. After a stabilization time, the detector is linked to the vacuum line to detect the helium gas flow through a leak. The full test cycle time averages 10 minutes, depending on the bag compartment size. Defects as small as 10 microns can be detected. Based on third-party validation studies, 12 micron defects were found to be the threshold of microbial ingress in rigorous Log-6 aerosol challenges. This breakthrough technology can also be used for bag and tubing assemblies with multiple single-use components.

Question 4

Can you explain the difference between pressure decay testing and what the HIT system offers?

To address integrity concerns, companies that manufacture single-use components will typically conduct a visual inspection as well as perform pressure decay testing. Pressure decay testing is the industry standard for validating single-use component integrity, however there are limitations to the level of assurance this testing can provide.

Pressure decay testing measures a drop in pressure within a bag body or vessel to determine the existence of a leak. This type of test method is limited in scope to stand-alone bag compartments and can be inhibited if the bag compartment is connected to tubing and other single-use components. The sensitivity of a pressure decay test was demonstrated to be 50 microns defect size for 50L bags and 100 micron for 200L bags. The cycle time for such a test could range from 10 minutes to upwards of 45-60 minutes depending on the equipment used and bag compartment size. Pressure decay testing is commonly used by bag manufacturers to ensure product quality prior to shipment.

Even though the product is tested at manufacturing, there is no guarantee that the components are still intact by the time they reach point of use. Shipping of these items can create possible breaches. After the box leaves the manufacturer, there are many potentially hazardous scenarios – dropping the box, box damage, Gamma irradiation and temperature extremes can all compromise the integrity of plastic single-use components. The HIT™ System was designed to allow end-users the option of point-of-use testing, thereby ensuring integrity immediately prior to usage.

Question 5

How long does it take to perform the HIT tests?

The full test cycle time, which includes loading and unloading the assembly, averages 10 minutes depending on the bag compartment size.

Question 6

What is your estimation of contamination risk reduction if HIT test performed versus pressure decay test?

The probability of defect catching microbes is proportional to the area of defect. Since pressure decay can detect only 100 micron defects while HIT detects 10 micron defects, the ratio of the areas is 100 times. Thus, risk of contamination of the bag is reduced by at least 100 times if HIT test is performed. This is conservative estimate that is based on defect area only. It does not take into account additional risk reduction associated with no observed penetration of aerosolized microbes through defects smaller than 10 micron.

Question 7

Why there is no penetration of microbes below 10 micron defect size in the aerosol challenge test while the size of bacteria is smaller than 10 micron?

Electric continuity data and previous scientific literature imply that surface tension prevents the formation of a liquid channel for a small defect which is likely the reason for non-penetration of aerosol-based microbes through a defect smaller than 10 micron inside sterile space.

Question 8

Can the HIT test compromise sterility of a single-use bag assembly?

Delivery of helium inside the bag is performed through a sterilization grade filter thus ensuring no contamination results from the test.

Question 9

Can you run the HIT test after using a single-use assembly in a process?

Fluid blocks defects in wet bags preventing the usage of Helium method for post-use integrity testing.

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