Anticipated production of intrathecals in pediatrics: towards to microbiological stability study
24 November 2020L. GUIRLE1, M.S. PIDOUX1, J. HELOURY1, B. DESSANE1, A. VENET1, V. SERVANT1, S. CRAUSTE-MANCIET1,2
1 Pharmaceutical Technology Department, Bordeaux University Hospital, France
2 ARNA ChemBioPharm U1212 INSERM – UMR 5320 CNRS, Bordeaux University, France
Intrathecals (IT) are currently prepared in our hospital pharmaceutical technology department with stability set to 8 hours. To easy the availability of the treatments over the weekends, and following a national survey showing poor stability data on the storage of ITs, we decided to perform microbiological studies to assess the risk of anticipated production for 72 hours.
We focused on drugs used for IT in our hospital: Methotrexate (MTX), Cytarabine, Prednisolone, Methylprednisolone (MTP) and Hydrocortisone (HCT). This study was based on the following steps: Microbiological sterility tests were conducted according to the European Pharmacopeia 10th edition by membrane filtration at H0 and H72. Method validation was performed accordingly (i.e. fertility test of culture media with 5 reference microbial strains Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans and Aspergillus brasiliensis and in addition Escherichia coli as potential source of contamination, applicability test of strains with drugs Methotrexate, Cytarabine, Methylprednisolone, Prednisolone, Hydrocortisone. The preparations were performed by aseptic transfer in a grade A IIb biosafety cabinet located in a grade B immediate environment and were stored protected from light at room temperature. Each drug was prepared in triplicate and each sample was assessed for sterility test. 6 syringes were prepared for each drug assessed, and 3 samples were sterility tested immediately after preparation (H0) and 3 after 72 hours (H72).
Sterility and fertility test of culture media were conclusive. Fertility test of strains with drugs showed no inhibition of bacterial growth by Methotrexate nor Cytarabine. No microbiological growth was observed on the samples at H0 and H72. Concerning corticosteroids, the study is still in process.
Our study showed that the sterility of our ITs preparations was kept for 72 hours using a validated method able to show microbiological growth. According to the recent GERPAC1 consensus conference on microbiological stability, we will now complete our study with integrity tests accordingly.
(1) S. Crauste-Manciet, I. Krämer, F. Lagarce, V. Sautou, A. Beaney, J. Smith, V. Fenton-May, J-D. Hecq, F. Sadeghipour and P. Le Brun – Guidance on the Assignment of Microbiological Shelf-life for Hospital Pharmacy Aseptic Preparations. Pharmaceutical Technology in Hospital Pharmacy, Volume 5, Issue 1, 20200001, eISSN 2365-242X, ISSN 2365-2411, DOI: https://doi.org/10.1515/pthp-2020-0001