Accurate and simplified pressure decay leak testing for single-use bioprocessing

The advancement of single-use technology is rapidly accelerating the evolution of bioprocessing applications, posing numerous benefits over traditional multi-use equipment. Single-use technology, specifically bioreactors, reduces the risk of cross-contamination between batches, increases flexibility, decreases cycle times for process skids, and eliminates costly, time-consuming cleaning steps. There is, however, a new challenge: This equipment is susceptible to system leaks.

Challenge: Leak testing single-use bioreactors

Single-use bioreactors (SUBs) are simply plastic bags that often arrive at the manufacturer pre-sterilized by gamma irradiation, already including all necessary single-use sensors. The bioreactor manufacturers conduct highly sensitive helium integrity tests as part of their in-house quality control measures. However, the bioreactor bag is then removed from the test setup, packaged, and shipped to the pharmaceutical manufacturer. It is then unboxed and installed into its holding container as part of a larger setup. These handling steps all introduce the potential for damage to the bag. As system integrity is critical for any bioprocess, it is common to conduct pressure decay tests at the point of use. However, conventional pressure testing methods pose additional challenges:

• Conventional pressure decay testing is not sensitive enough to detect small leaks.
• Helium integrity testing is highly time-consuming and introduces an unnecessary gas into the cleanroom environment.

Solution: One device to control pressure and monitor mass flow

Fast and accurate leak testing can require a rather complex setup. When the device is under test, in this case, the SUB is subjected to constant pressure within a closed system, any resulting flow is a direct measure of the leak rate. This type of test requires both stable pressure control at the SUB and accurate flow measurement to test for leakage. Leaks are most easily detected and measured when the meter generates minimal pressure drop. Because of this, Alicat recommends using a single Whisper-Series mass flow controller. This device has a full-scale pressure drop as low as 3.6 mbar (0.052 PSID) and a turned-down pressure drop as low as 0.018 mbar (.00026 PSID), allowing for precise and responsive control with minimal frictional resistance. It can be set to maintain a constant pressure at the SUB while providing accurate mass and volumetric flow readings in real-time. Configured this way, a Whisper-Series device functions as a simultaneous pressure controller and mass flow meter. This method requires only one device, making it faster and easier to test single-use equipment for leaks. It is faster and more sensitive than a pressure decay test, and simpler and lower cost than a multi-device leak checking system.