The Biologics Testing Solutions group at Charles River provides microbiology services to support our clients’ lot release programs, manufacturing, and stability testing needs. Testing is performed according to the many different compendial methods outlined by the global regulatory bodies.
Medical devices, biologics, veterinary products and pharmaceutical products labeled as sterile require bioburden, sterility and endotoxin testing.
Bioburden (ISO 11737-1, USP <61>, USP <62>, EP 2.6.12, EP 2.6.13, JP 4.05)
This test is designed to determine the number of viable aerobic microorganisms, which in turn determines the sterilization dose required for the sterility test.
Sterility (EP 2.6.1, USP <71>, JP 4.06)
Charles River’s sterility testing complies with the requirements of the USP, EP and current FDA regulations. Sterility testing is conducted by direct inoculation or membrane filtration methods, and can be performed in an isolator or cleanroom environment. In conjunction with the sterility test, a bacteriostasis/fungistasis test is performed to assess whether the test article is inhibitory to the growth of microorganisms. Additionally, vaporized hydrogen peroxide (VHP) ingress testing is available for sterility testing that is performed within an isolator that undergoes VHP decontamination. This assay evaluates if VHP ingress into a test article container is evident, which may affect the validity of the sterility testing results.
Endotoxin Testing (EP 2.6.14, USP <85>, JP 4.01)
In vitro bacterial endotoxin testing has been available to our clients for many years. These assays meet all pharmacopeia requirements, including gel-clot, which is a qualitative assay, and kinetic turbidimetric and chromogenic methods, which are quantitative assays. We provide preliminary screening and validation of products as well as backup technical services. Charles River also provides in vivo pyrogen (EP 2.6.8, USP <151>) and monocyte activation testing (MAT) (EP 2.6.30) for those materials for which endotoxin testing is not appropriate or is insufficient.
Finished products and active pharmaceutical ingredients (APIs) that are not required to be sterile may be tested for bacterial and fungal counts and the absence of specific pathogens. Other products, such as creams and ointments, may require preservative efficacy testing.
Microbial limits test: This test is designed primarily to allow quantitative enumeration of bacteria and fungi that may grow under aerobic conditions (EP 2.6.12, EP 2.6.13, USP <61>, USP <62>, JP 4.05).
Preservative efficacy testing: Antimicrobial preservatives may be added to a pharmaceutical preparation if the preparation itself does not have adequate antimicrobial activity. The efficacy of the antimicrobial preservative may be demonstrated by testing (EP 5.1.3, USP <51>).
OTHER MICROBIAL TESTING CAPABILITIES
Cytotoxicity: Detects the presence of toxins in medical devices and their components or in raw materials (ISO10993 Part 5, USP <87>).
Water analysis: Provides the total viable and coliform organism counts required for process water.
Mycoplasma: Determines whether mycoplasma is present in a test article (agar-cultivable and non-cultivable, and PCR).
Mycoplasmastasis: Determines if a test article is inhibitory to the growth of mycoplasma (EU and USP requirements).
Spiroplasma: Detects whether spiroplasma is present in a test article and applies to products produced in insect and plant cells (PCR).
Mycobacterium: Determines whether mycobacterium species are present in the test article and is important for cell-derived vaccine products.
Disinfectant testing: Offered in compliance with the Biocidal Products Directive (BPD)-98/8/EC to verify the efficacy of disinfectant programs for cleanrooms or other controlled areas.
Antibiotic testing: Follows the specifications of the EP and USP, and evaluates the potency (or activity) of an antibiotic by its inhibitory effect on microorganisms.
Environmental monitoring: Offered to companies with on-site cleanrooms of various grades; Charles River can either perform the monitoring for clients or train their operational staff. Sample incubation and reporting is also available.
EXPLORATORY MICROBIAL ACTIVITIES
The second key function of our microbiology group is to provide bacterial challenge material for vaccine studies. We perform exploratory work on bacterial isolates, prepare the challenge material and conduct analysis of organs and blood samples upon completion of the study. These activities are carried out in dedicated facilities.