The high value of growth media and the length of time required for a typical cell culture process call for the highest degree of scrutiny when setting up such a run. A leaking bioreactor would generate an important financial loss and jeopardize the carefully timed production schedule in a GMP facility. In vaccine processes, it might also pose a risk to operator safety.
Today, single-use technology is well accepted and the manufacturer’s quality assurance program ensures leak-free single-use bags upon delivery. But what about the risks involved with installation and other handling errors? Training of operators is mandatory, but should it be the only way to mitigate against failures?
A post-installation pre-use test of the entire bioreactor system (including tubing) capable of detecting typical leaks that might have been introduced due to operator handling errors would greatly improve risk-mitigation capabilities in single-use production facilities. A critical example of this situation is the absolute need for proper connection of different tubing elements during bioreactor setup, media preparation, and inoculum transfer because it is at this point that an operator error might immediately result in a leakage.
More than 40 different test methods have been proposed for leak detection based on various technologies such as “sniffers” (for special gases that are used as leak testing agents), thermal imaging, flow measurement, and pressure decay and pressure increase.
Each technology has its own strengths and weaknesses in terms of sensitivity, feasibility, and cost. All these factors have to be carefully considered and balanced when developing a suitable bag-testing device for single-use bioreactors that are designed to make their way into GMP production facilities for vaccine-, monoclonal antibody-, and recombinant-protein-producing companies.
Risk assessment reveals that a predictive leak test for single-use bioreactors has to be performed at the point of use (pre-use but postinstallation). Therefore, testing a single-use bioreactor bag in a separate device as is usually done when applying gas sniffer technology and then installing it into its bag holder would not permit the detection of operator handling errors.
Pressure-decay technology, on the other hand, can be used to test the single-use bioreactor bag after installation in its final configuration directly in its holder. This approach presents a reliable and predictive risk mitigation tool.