Last week, we finished our Ask the Expert discussion on ensuring integrity and sterility of single-use assemblies for manufacturing. Several questions were asked about how to perform integrity testing and the ways in which sterility of single-use assemblies can be compromised. Other questions involved reducing contamination risk with testing and current quality testing methods.

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. These topics were also covered during last week’s Ask the Expert Session.

The session hosted by Carla Conant, Global Product Manager, ATMI LifeSciences, received several questions about ensuring quality while using single use systems. Ms. Conant provided a wealth of information based on her extensive experience with quality testing systems for single-use assemblies.

Question topics included:

• How to perform integrity testing
• Ways sterility of single-use bags can be compromised
• Reduction of contamination risk with testing
• Current quality testing methods
• Components recommended for testing

I have selected a few of the submitted questions and answers to include below. For a full list of questions and answers, please see Ask the Expert discussion on ensuring integrity and sterility of single-use assemblies for manufacturing.

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

The Answer:

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.

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 Answer:

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.

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

The Answer:

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.

Please visit this week’s Ask the Expert session – “Innovations in Cultureware” hosted by Dr. Graziella Mendonsa , Product Manager, MIDSCI.