Faster Sterility Tests for Biological Products

The FDA Center for Biologics Evaluation and Research (CBER) in Rockville, MD, published a poster that considers rapid sterility testing and compares different modern methods with compendial methods. Seema Parveen, Simleen Kaur, James L. Kenney, William M. McCormick and Rajesh K. Gupta, researchers in the Division of Product Quality (DPQ) in the Office of Compliance and Biologics Quality (OCBQ) are working to reduce the expenditure of time for classic sterility testing by evaluating rapid microbial methods for sterility testing of biologicals.

The alternative methods they evaluated are:

- Direct inoculation into standard aerobic and anaerobic liquid media
- Early detection of bacterial growth based on CO2 fluorimetric detection

- Direction inoculation into iAST and iNST liquid media
- Detection of bacterial growth based on CO2 colorimetric detection

Rapid MilliflexR
- Growth on solid media: Tryptic soy agar (TSA), Sabouraud dextrose agar (SDA), and Schaedler blood agar (SBA)
- Inoculum filtered by membrane; membrane sprayed with ATP releasing and bioluminescence reagents
- Photons generated ATP bioluminescence are captured and detected by photon counting imaging tube; picture displayed on computer monitor.
  Some colonies identified even before visual growth on medium.

(more details about these methods can be found in the RMM database in the members' area of the ECA RMM Working Group)

Major Findings:

  • Compendial method, Rapid Milliflex, BacT/Alert, and BACTEC showed equivalent sensitivity at detection of lowest spiked microorganism level.
  • Milliflex Detection System detected the lowest spiked of P. acnes and B. vulgatus within 5 days versus 9-10 days for compendial sterility method, BacT/Alert, and BACTEC.
  • Milliflex consistently detected spiked organisms at 1 CFU/10 ml within 5 days (usually 1-3 days). Similar results were obtained at 10 and 100 CFU/10 ml.
  • Solid media (TSA, SDA, and SBA) showed faster growth of spiked organisms (within 5 days) compared to liquid medium.
  • BACTEC and BacT/ALERT did not show growth in experiments using matrix containing thimerosal for most of the microorganisms.
  • Unlike TSA and SDA media, SBA supported growth of spiked organism in the presence of thimerosal and after treatment

Axel H. Schroeder
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)

Go back


Stay informed with the GMP Newsletters from ECA

GMP Newsletter

The ECA offers various free of charge GMP newsletters for which you can subscribe to according to your needs.

To subscribe, please click here.