Sterility testing of cell lines, media, in-process material and final products must be demonstrated during the manufacture of pharmaceuticals and medical devices.
BioReliance offers the following tests under GLP or GMP:
- Direct Inoculation Sterility for Final Bulk
- Direct Inoculation Sterility for Final Vials
- Direct Inoculation Sterility for Prebanking or Cells at limit
- Direct Inoculation Sterility for Unprocessed Bulk
- Direct Inoculation Sterility for Cells and Virus Banks
- Membrane Filtration Sterility
BioReliance sterility test assays comply with standards specified in USP <71> and with the European and Japanese Pharmacopeia and the US Food and Drug Administration (FDA) GMP 21 CFR 610.12.
All sterility testing assays are performed in an ISO Class 5 Sterility Suite to meet regulatory standards worldwide for production of safe pharmaceuticals. We typically employ the two media method in order to detect both aerobic and anaerobic bacteria as well as fungi.
To learn more about the two media method please see - Meeting USP/EP/CFR sterility testing requirements with two media
What types of sterility testing do you offer?
BioReliance provides three basic types of sterility testing.
1. Direct inoculation (immersion)
Sterility testing of unprocessed and final bulk, final vials, prebanking cells, and cell and virus banks is typically performed by directly inoculating the test article into 2 different types of media that support the growth of aerobic and anaerobic bacteria respectively. Test articles are incubated for 14 days followed by testing for microbial contaminants. Note - Fungi are also detected.
The advantages of the direct inoculation method are:
- sterility testing for materials that cannot be easily filtered
- smaller volumes of test article can be used
The key to low false positive rates and reducing out-of-specification is to prevent contamination from naturally occurring bacteria and fungi. To address this, BIoReliance performs all sterility testing in ISO Class 5 sterility suites that are continually monitored to eliminate naturally contaminants.
2. Membrane Filtration
To address issues such as large volumes of test articles and the potential presence of inhibitors that interfere with microbial growth, BioReliance employs membrane filtration to test for bacteriostatic and fungistatic activity. In this method, bulk articles or effluent from vials of final products are passed through a membrane filter designed to retain microbial contaminants.
The filters are rinsed to remove inhibitors and then incubated in two types of media and assayed exactly as in the direct inoculation method described above.
Advantages of the membrane filtration method include:
- accommodation of large volume samples (up to 500 ml)
- removal of inhibitory substances that inhibit the growth of microorganisms by rinsing the filter membrane with a suitable agent.
3. Direct transfer
Medical devices, solid dose forms, ointments, and creams can be directly immersed in growth media to test for bacteriostatic and fungistatic activity according to ISO Standards. Microbial detection is performed essentially like direct inoculation after a 14 day incubation. BioReliance offers custom protocols to accommodate parts of devices and solids and will work with you to determine the best way to test your articles.
For test articles produced by non-aseptic manufacturing processes, a bioburden (or microbial limits) detection assay should be performed. Furthermore often, it is necessary to evaluate a non-sterile test article for the presence of U.S. FDA criteria for “objectionable organisms.” A microbial limit approach is recommended for the evaluation for objectionable organisms.
According to USP <71>, BioReliance performs a Suitability (Growth Promotion Test) and Validation Test (Bacteriostasis and fungistasis Test). The bacteriostasis and fungistasis test determines whether the test article is inhibitory to the growth of microorganisms. If microorganisms can’t be recovered from the device in the growth medium due to device characteristics, subsequent tests may be required to compensate for any inhibiting effects (as by antibacterial coatings) and to obtain true sterilization assurance.