Ensuring product sterility is critical to patient health and safety. Sterility testing is an essential procedure as part of pharmaceutical manufacturing, and can be one of the most time-consuming quality tests. The test, typically 14 days in length is often a bottleneck in the manufacturing process. Final products cannot be released until all QC testing, and particularly the sterility test is complete. In certain manufacturing environments, such as vaccine production, sterility testing is required during manufacturing, creating delays.
As identified in its report on re-engineering influenza vaccine production, the President’s Council of Advisors on Science and Technology (PCAST) noted, “Each batch of vaccine material must pass a sterility test to ensure that it is not contaminated with bacteria or fungi. While current methods of doing this are reliable, they take approximately two weeks. More rapid sterility test methods are available and could cut the time for vaccine release by at least a week1.”
With the introduction and increased acceptance of rapid microbiological methods (RMM), new technologies are available to accelerate the traditional microbial quality control lab testing process for sterility while adhering to the stringent regulatory requirements of the industry.
One such technology is the Growth Direct™ System, which can provide sterility test results in about 7 days versus the 14 day traditional test, while automating the incubation, detection and reporting of results. The instrument replicates the aerobic and anaerobic conditions of the current method and can detect growing colonies starting within hours.
Rapid Sterility Testing Reduces Process and Production Delays
The Growth Direct System reduces delays by accelerating and automating the sterility test. The method leverages similar sample preparation techniques to the traditional sterility test, helping to ensure user adoption.
Automating the Sterility Test
Users prepare samples using familiar techniques and load those samples into the instrument for incubation, detection, and reporting, reducing the need to retrain personnel in new sample preparation processes. Sterility test preparation with the Growth Direct System leverages the existing pumps common with sterility testing to provide a closed loop environment. The test can be performed in an isolator, a biological safety cabinet or in other sterile environments. During the test users performs similar sample preparation steps using Growth Direct Sterility Cassettes. The prepared samples are then loaded into the instrument.
Once samples are loaded, the instrument automates the rest of the testing process. This provides several areas of time and cost savings, including:
Initial Results Starting Within Hours:
Figure 1. Growth Direct Sterility Cassette with Growing ColoniesThe Growth Direct System can start to detect growing colonies within the first 24 hours of testing. An email can be sent alerting the lab of a positive result. In the case of a sterility failure, email alerts provide immediate warning, giving the lab critical time to take action.
Final Results in 7 Days:
The traditional sterility test is 14 days, but the Growth Direct System can produce final results in half the time. Considering that certain manufacturing processes can require sterility tests at multiple stages, the time savings can be significant.
Non-Destructive Test
Figure 2. The Growth Direct™ SystemBecause the Growth Direct System is a growth-based test, with colonies growing on a membrane, once visible, the colonies are available for investigation steps such as identification. This eliminates the re-culture step required with the traditional sterility test.
Fewer Time-Consuming Tasks
Automation reduces time-consuming tasks involved in the sterility testing process. Growth Direct System users prepare samples using familiar techniques, and the instrument handles incubation, detection and reporting. Ultimately, less time spent on microbial testing means more time allocated to higher value activities in the lab.
Faster Times to Market
Faster sterility results impact the entire organization. Because sterility testing can be the gating test for production, rapid results can accelerate production and time to market. In an industry as competitive as pharmaceuticals, saving a few days can be significant.
Sterility testing with the Growth Direct System reduces the time to result from 14 days to about 7 days. Considering the production environment and the number of in-process steps that require sterility testing, the overall time savings could be between 14 and 21 days.
A rapid sterility test means faster production, release and distribution of critical pharmaceuticals. In a scenario where timing is critical, rapid quality control testing is imperative.
References/Notes
- President’s Council of Advisors on Science and Technology. REPORT TO THE PRESIDENT ON REENGINEERING THE INFLUENZA VACCINE PRODUCTION ENTERPRISE TO MEET THE CHALLENGES OF PANDEMIC INFLUENZA. August 2010. p. ix
This work was supported by the Biomedical Advanced Research and Development Authority Contract Number HHSO100201000056C