Preliminary validation results of an alternative sterility test for hospital injectable anticancer drugs
3 October 2024
Y. Ghomari1,2, T. Martin2, P-H. François2, A. Bendjama2, P. Coliat21: Faculty of Pharmacy, University of Lille, FRANCE
2: Pharmacy Department, Institut de Cancérologie Strasbourg Europe - ICANS, Strasbourg, FRANCE
Background
For batch production of injectable anticancer drugs, the sterility test outlined in the European Pharmacopoeia (Ph.Eur) is not well-suited to practical use. Nevertheless, automated CO2 growth detection systems providing rapid results are currently available. While alternative methods validated according to Ph.Eur standards can be employed, practical applications are poorly detailed. This study presents the preliminary validation results of an alternative sterility testing method adapted for batch production of injectable anticancer drugs in hospital pharmacy.
Method
Specificity and applicability tests were performed. The BD BACTEC®Microbial Incubation and Detection system was used with BD BACTEC™ Plus Aerobic/F vials for aerobic strains and BD BACTEC™ Lytic Anaerobic vials for anaerobic strains. The microbial strains tested were those recommended by Ph.Eur 2.6.1 as well as two commensal strains. Each strain was inoculated in triplicate with 10 to 100 colony-forming units (CFU) in sterile isotonic saline solution, a 2 mg/mL Carboplatin solution, and a 4 mg/mL Pembrolizumab solution. Tests were incubated at 35°C with negative controls (NC). Vial positivity and time to detection (TTD) of strains were measured. A Student’s t-test (two-tailed, α=5%) was used to compare TTD means.
Results
The BACTEC® system detected all the microbial strains in less than 48 hours. TTD between saline, carboplatin, and pembrolizumab solutions was not significantly different, except for carboplatin, which significantly prolonged (p<0.05) the detection of Bacillus subtilis and Candida albicans. NC remained negative after 14 days of incubation.
Conclusion
These initial results are encouraging and support the use of the BACTEC® system as an alternative method of sterility testing for injectable anticancer preparations. However, limit of detection testing, testing with the Ph.Eur compendial method, and trials with other anticancer drugs should be performed for the complete validation of the method.