TCH-044 Sterility Testing Using a Rapid Microbiological Method For Batch Production of Cytotoxic Drugs in a Hospital Pharmacy. (12th March 2013) - Matheron, A
Abstract : Background: To improve the quality of sterile cytotoxic drug preparation in hospital pharmacy, we implemented batch production of standardised doses of 11 cytotoxics and 1 monoclonal antibody using the Repeater pump (Baxa, Baxter). In accordance with French good manufacturing practise for hospital pharmacies [1], physicochemical and sterility tests have to be implemented for batch release. Purpose: To investigate the possible use of a rapid microbiological method (BD Bactec) for sterility testing of batches of cytotoxic drugs. Materials and Methods: Taking into account the possible inhibition of microorganism growth with cytotoxics [2–4], we investigated the detection of microbial growth of cytotoxic bags with the Bactec system (CO2 detection by fluorescence) when inoculated with <100 Colony-Forming Units (CFUs) of 4 microorganisms recommended in the European Pharmacopeia [5] (Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), Bacillus subtilis (BS) and Candida albicans (CA)) and 3 microorganisms usually found in clean rooms (Staphylococcus epidermidis (SE), Escherichia coli (EC) and Enterococcus faecalis (EF)). Results: All species were detected in only cyclophosphamide and trastuzumab, while conversely 5 fluorouracil (5FU) inhibited the growth of all microbial species. For 5FU, the use of an alternative device (Bact/Alert, Biomerieux) with CO2 detection by colorimetric method or the 1/10 dilution of the 5FU solution, allowed growth to recover for Staphylococcus species, Candida albicans and Escherichia coli. For most of the remaining drugs, Pseudomonas aeruginosa and Bacillus subtilis seemed to be routinely inhibited. Conclusions: Further dilutions of cytotoxic bags or use of Bact/Alert are planned to improve the results. Moreover, the combination of sterility tests with the Bacterial Endotoxin Test [6–7] would help improve the results for Gram-negative bacteria. References: Afssaps – Good manufacturing practise – November 2007. Krämer I. Viability of microorganisms in novel antineoplastic and antiviral drug solutions. J Oncol Pharm Practice. 4(1); 1998. 32–37. Paris I, Paci A, et al, Microbial growth tests in anti-neoplastic injectable solutions. J Oncol Pharm Practice (2005) 11: 7–12. Rawal BD. Variation in microbial survival and growth in intravenous fluids. Chemotherapy 1985; 31(4): 318–323. European Pharmacopeia 7.2 – Biological methods – Chapter 2.6.1 Sterility. EDQM United States Pharmacopeia, General Chapter <85> Bacterial Endotoxins Test. United States Pharmacopeial Convention: Rockville, MD. Guidance for Industry – Pyrogen and Endotoxins Testing: Questions and Answers on http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM310098.pdf consulted 10 October 2012. No conflict of interest.