Filtration is a common method of sterilizing drug product solutions. VxP Pharma understands the importance of qualified aseptic filtration and can provide filter function evaluation and validation studies for a variety of filters and drug products to insure:
- Low extractables
- Low membrane protein binding
- Faster flow rate and throughput
- Chemical compatibility
- Microbial retention
- Filter performance reproducibility
- Sterilization
- Integrity testing and qualification
- Faster flow rate and throughput
- Removal of particulates.
Sterilization
To evaluate and validate use of a sterilizing-grade filters, it is necessary to prove that the filter is adequately sterilized and that the sterilization method does not damage the filter. There are many filter sterilization methods available, but moist heat (steam) is the preferred option. Important considerations for steam sterilization of filters are autoclave cycle time, number of cycles, and cycle development. Some of the filter sterilization services include:
- Autoclave validation
- Hot-spot/Cold-spot mapping studies
- Thermocouple analysis
- BI analysis
Integrity Testing
Integrity testing can be performed prior to processing, and should be routinely performed post-use. It is important that integrity testing be conducted after filtration to detect any filter leaks or perforations that might have occurred during the filtration. Qualification of integrity testing is necessary as well as to qualify the test accuracy and reproducibility of the instrument. Filter integrity tests that are commonly used include:
- Bubble point
- Forward flow
Microbial Retention
It is important to demonstrate microbial retention with a specific filter and drug product to ensure the filter is not undergoing degradation, deformation or some other changes under the conditions of use. Initially, a filter is qualified as sterilizing grade by the filter manufacturer, based on its ability to retain high levels of microorganisms, as demonstrated by the results of the microbial retention test. Microbial retention validation should include microbiological challenges to simulate worst-case production conditions for the product/material to be filtered and integrity test results of the filters used. Product bioburden should be evaluated when selecting a suitable challenge organism representing the worst-case challenge to the filter. VxP Pharma can provide a variety of microbial retention testing services for your filter evaluation/validation needs.
Filter Inertness
Every aseptic filter is theoretically inert, meaning the filter material should neither add anything to the drug product nor remove anything from it, but this is an ideal expectation. A small amount of extraction or adsorption is a possibility with any commercially available filters, depending on the nature of the drug product and the filter material and construction. The scientists can determine filter inertness through many techniques, including:
- Gravimetric Extractables
- Adsorption studies
- Chemical compatibility
- Oxidizable substances
- pH/Conductivity
- Weight changes
- Formulation analysis
- Advanced analytical techniques
Particulates & Fibers
Particulates and fibers are materials that consist of mobile, randomly-sourced, extraneous substances that cannot be quantitated by chemical analysis due to its heterogeneous composition. It is crucial to determine the source of particulates/fibers, as the filter itself may be found to contribute to the particle load. Testing for fibers, just as particulates, will determine if the filter is shedding fibers into the solution or the filter’s function is completely removing the fibers. Two common tests that determine particulate matter include:
- Liquid particle count
- Light obscuration method
Filter Function Validation
The purpose of filter validation is to ensure filter performance and product reproducibility for every manufacturing lot. VxP Pharma can provide complete validation services on a variety of filters to ensure your drug product and filters are efficiently compatable and working correctly.