Development of a challenged Media Fill Test for aseptic process qualification of a pediatric parenteral nutrition compounder.
2 ARNA ChemBioPharm U1212 INSERM – UMR 5320 CNRS, Bordeaux University, France
A physico-chemical and microbiological plan is established to qualify a new pediatric parenteral nutrition (PPN) compounder: the BAXA® ExactaMix 2400. For aseptic process validation, we decided to implement a challenged Media Fill Test to improve the sensitivity.
PPN are produced in an ISO grade 5 horizontal Laminar Airflow Cabinet where the parenteral nutrition compounder is located. Several premix solutions are performed in parallel in a Biological Safety Cabinets class IIB both located in a grade B environment. For the Media Fill Test (MFT), all drugs solutions are substituted by culture media (tryptone soja broth). All the tests are made according to simulate a real production. MFT suits for pharmaceutical industry production. But, for hospitals, level of production is too low to safely reveal microbial contamination occurrence. So we decide to develop challenged MFT (cMFT). It consists to a classical MFT where surfaces are intentionally contaminated with microorganisms1. To select surfaces at risk we performed Failure Mode, Effects and Criticality Analysis (FEMEA). For this analysis, 4 short meetings including technicians and pharmacists were planned to identify the failure modes and their criticality for each step of the production of PN.
FEMEA analysis showed 47 failure modes. Among them preparation process cumulated 19 failures modes. The most critical steps identified were the disinfection of the upper surfaces of vials stoppers with a criticality highest score at 80 and aseptic failure during the manipulation such as misuse of gloves, scored at 60. Thus, we decided that the surfaces, which will be intentionally contaminated during the cMFT, will be the upper surfaces of vials stoppers, the valve set, and the manipulator gloves. According to a previous work1 we selected Escherichia coli as challenge microorganism at 106 CFU/mL final concentration. It’s a fast-growing commensal bacterium, an opportunist pathogen and referenced at European Pharmacopeia. It’s important to choose a noncommon cutaneous commensal bacterium to point out an aseptic compounding failure. The method is performed following the classical MFT. Each final preparation is incubated for 7 days at 32°C and 7 days at ambient temperature. All steps of aseptic technique are assessed by visual inspection: good cleaning, disinfecting procedures, hand hygiene and garbing practices use in ISO class 5 aseptic working area. If all steps are followed, the closed system is maintained, and no contamination appears.
Qualifications of pediatric PN compounder are essential to guaranty sterility and quality of production. These correspond to good manufacturing practices. The MFTc enhances the sensibility of the MFT, and can highlight possible deviations of the aseptic process. This practice could be applied to improve the safety of other sterile productions.
1 Sigward, E., Fourgeaud, M., Vazquez, R., Guerrault-Moro, M.-N., Brossard, D., Crauste-Manciet, S.
Aseptic simulation test challenged with microorganisms for validation of pharmacy operators
(2012) American Journal of Health-System Pharmacy, 69 (14), pp. 1218-1224.
2 M.-A. Gratelle, Evaluation des Pratiques Professionnelles liées au processus de production des nutritions parentérales pédiatriques au Centre Hospitalier Universitaire de Bordeaux, thèse d’exercice, Limoges, 2016