Pharmaceutical product sterility is non-negotiable. When a single contaminant can put patient health and safety at risk, you can’t afford to leave anything to chance.
Filter integrity testing is a critical validation process for pharmaceutical filters. It ensures your filtration system performs as intended to protect patients, maintain product quality, and prevent costly losses.
What is filter integrity testing?
Filter integrity testing verifies the structural integrity of a filter and its ability to remove contaminants to the required standard. In the pharmaceutical and healthcare industries, manufacturers favour non-destructive filter integrity testing methods. These provide meaningful results while allowing you to use the filter in production.
Destructive vs non-destructive methods
Destructive testing involves directly challenging the filter with bacteria to verify retention capabilities. You’ll typically test a sample filter from each production batch during quality control.
Non-destructive testing verifies filter integrity without compromising usability. They require you to fill the filter's pores with liquid (usually water) and pressurise the system. This pressurisation causes air molecules to diffuse through the water in the pores creating a measurable flow, which correlates to the filter's ability to remove bacteria and, therefore, its integrity.
Filer manufacturers use non-destructive testing methods to confirm the integrity of every filter before and after production.
Filter integrity testing equipment
Modern integrity testing relies on automated electronic equipment to conduct tests, providing clear pass/fail results.
Automated systems offer several advantages for operators. For example, you can set passwords to protect key functions within the testing equipment to prevent unauthorised access. Additionally, you can programme the equipment with filter-specific parameters to minimise operator errors and ensure accurate results.
3 reasons filter integrity testing is essential in pharmaceutical production
1. Product sterility
Sterility is essential for parenteral (injectable) products, as they bypass many of the body's natural defences. Filter integrity testing provides documentary evidence that the filtration system can remove bacteria from the liquid being processed and help you to produce sterile products.
2. Preventing product loss
When a filter integrity test fails after product filtration, manufacturers often have to discard the entire batch. Depending on the product, this could represent over a million dollars. Filter integrity testing provides a crucial safety net which helps to protect your investment.
3. Complying with industry regulations
Regulatory bodies, including the Food and Drug Administration (FDA), require you to test filter integrity after each batch. They also recommend filter integrity testing pre-filtration. Testing filters at each stage of the manufacturing process creates a complete validation loop, ensuring your products remain sterile throughout.
Filter integrity testing methods
Diffusion flow test
The diffusion flow test is the most common method for testing filters used with liquids. This test works on the principle that gas molecules migrate through a wetted membrane's pores following Fick's law of diffusion.
The diffusion test involves:
- Thoroughly wetting the filter with appropriate test fluid
- Increasing upstream pressure to approximately 80% of the minimum bubble point
- Allowing the system to equilibrate
- Measuring the gas flow at the outlet
- Comparing results against manufacturer specifications
Bubble point test
The bubble point test determines the minimum pressure required to force liquid out of the pores of a wetted filter – correlating to the largest pore size. As such, bubble points tests indicate the point at which bubbles begin to appear, which reveal any defects or inconsistencies in the filter's pore size and overall structural integrity.
Bubble point tests typically follow these steps:
- Thoroughly wetting the filter
- Gradually increasing upstream pressure
- Observing downstream equipment for continuous bubbling
- Comparing the pressure at which bubbling occurs against manufacturer specifications
Water intrusion test
The water intrusion test serves hydrophobic filters, such as polytetrafluoroethylene (PTFE) membrane vent filters. Since these filters repel water, this test measures the rate water passes into the hydrophobic membrane under pressure.
Water intrusion tests require:
- Placing water on the upstream side of the hydrophobic filter (no pre-wetting required)
- Gradually increasing pressure to the manufacturer's specified test pressure
- Allowing the system to stabilise for the recommended time
- Measuring the amount of water intrusion into the filter membrane
- Comparing the intrusion rate against the manufacturer's specifications to determine if the filter passes or fails
Pressure hold test
The pressure hold (or pressure decay) test involves pressurising the upstream side of a wetted filter and monitoring pressure decay over time. Any decline in pressure beyond specifications indicates a potential integrity issue.
A standard pressure hold involves:
- Thoroughly wetting the filter with the appropriate test fluid
- Pressurising the upstream side to the manufacturer's specified test pressure
- Isolating the upstream pressure by closing the inlet valve
- Monitoring the upstream pressure for a specified period (usually 5-10 minutes)
- Calculating the pressure decay rate
- Comparing the pressure decay rate with manufacturer specifications to determine if the filter passes or fails
How to find the right method for your application
Finding the appropriate testing method depends on several factors, including the:
- Type of filter (hydrophilic vs hydrophobic)
- Production stage
- Application criticality
We recommend using diffusion-based tests for liquid filtration in final product manufacturing and water intrusion tests for tank vent filters. The most important advice is to consult with your filter supplier. As filtration experts, they'll help you find the optimal testing method for your application.
Common pitfalls to watch out for
Even with the right equipment and methods, it only takes a single mistake to compromise the validity of your tests.
Incomplete wetting
Improper wetting is the most common cause of false failures in diffusion and bubble point tests. If you don’t take the time to wet every pore, air will pass through the dry areas, mimicking what you’d expect to see from a damaged (or non-integral) filter.
Dirty filters
Residual product on filters can interfere with integrity test results. Proper cleaning procedures between production and testing are essential to ensure accurate readings.
Improper equipment setup
Incorrectly programmed testing equipment is another common source of failures. For example:
- Entering the wrong filter parameters
- Inaccurate volume measurements
- Incorrect test pressure settings
- Improper valve configurations
One manufacturer contacted us after experiencing persistent filter failures. Before conducting a filter integrity test, it's essential to vent all the air from the system. Upon visiting the site, we discovered the vent filters on top of the system were positioned sideways, which prevented proper venting during the wetting process. Simply repositioning the filter upright immediately resolved the issue.
The future of filter integrity testing: PUPSIT
The regulatory push toward pre-use, post-sterilisation integrity testing (PUPSIT) marks a significant development in the pharmaceutical industry.
PUPSIT aims to reduce the risk of contamination in pharmaceutical products and improve patient safety. However, it presents some practical challenges to pharmaceutical manufactures. For one thing, PUPSIT requires you to manipulate the sterilised system. Implementing it into established filtration processes can also cause disruption, as it requires additional operator training.
Despite these challenges, industry trends suggest PUPSIT will become the regulatory standard in the coming years. So, preparing today could save you hassle tomorrow.
Integrity by design: transforming your approach to filter testing
Filter integrity testing isn’t a checkbox exercise – it's a critical component of pharmaceutical manufacturing. Proper testing helps to ensure product sterility, prevent costly product losses, and maintain regulatory compliance.
By understanding the different testing methods and following best practices, you can avoid common pitfalls and ensure reliable results. When in doubt, consult with filtration experts who can provide guidance specific to your applications and help troubleshoot issues that may arise.
