title: Environmental contamination by cyclophosphamide preparation: Comparison of conventional manual production in biological safety cabinet and robot-assisted production by APOTECAchemo.
abstract: OBJECTIVE
  The aim of this study was to compare environmental contamination of cyclophosphamide (CP) during 1 week of drug compounding by conventional manual procedure in a biological safety cabinet (BSC) with laminar airflow and a new robotic drug preparation system (APOTECAchemo).
  
  
  METHODS
  During four consecutive days, similar numbers of infusion bags with cyclophosphamide were prepared with both techniques in a cross-over design. Wipe samples (49 for BSC, 50 for APOTECAchemo) were taken at several locations (gloves, infusion bags, trays, BSC-benches, floor) in the pharmacy and analyzed for CP concentrations by GC-MSMS (LOD 0.2 ng/sample).
  
  
  RESULTS
  The detection rate was 70% in the BSC versus 15% in APOTECAchemo. During manual preparation of admixtures using BSC contamination with CP was below 0.001 ng/cm(2) at most locations, but significant on gloves (0.0004-0.0967 ng/cm(2)) and the majority (70%) of infusion bags (<0.0004-2.89 ng/cm(2)). During robotic preparation by APOTECAchemo, gloves (1 of 8: 0.0007 ng/cm(2)) and infusion bags (3 of 20: 0.0005, 0.0019, 0.0094 ng/cm(2)) were considerably less contaminated. Residual contamination was found on the surfaces under the dosing device in the compounding area (0.0293-0.1603 ng/cm(2)) inside the robotic system.
  
  
  CONCLUSIONS
  Compared to outcomes of other studies, our results underline good manufacturing procedures in this pharmacy with low contamination for both techniques (BSC and APOTECAchemo). Comparison of both preparation procedures validated that contamination of infusion bags was much lower by using the robotic system.
authors.affiliation: Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig Maximilians University of Munich, Germany Rudolf.Schierl@med.uni-muenchen.de.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schierl
authors.affiliation: Scientific Institute of Romagna for the Investigation and Treatment of Tumors (IRST), Meldola (FC), Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Masini
authors.affiliation: Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig Maximilians University of Munich, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Groeneveld
authors.affiliation: Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig Maximilians University of Munich, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Fischer
authors.affiliation: Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig Maximilians University of Munich, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Böhlandt
authors.affiliation: Loccioni Humancare, Moie di Maiolati (AN), Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Rosini
authors.affiliation: Loccioni Humancare, Moie di Maiolati (AN), Italy.
authors.forename: Demis
authors.initials: D
authors.lastname: Paolucci
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D003520:Cyclophosphamide / Q000737:chemistry*; D004340:Drug Contamination / Q000517:prevention & control; D004784:Environmental Monitoring / Q000379:methods; D004866:Equipment Contamination / Q000517:prevention & control*; D016273:Occupational Exposure / Q000517:prevention & control; D010594:Pharmacies; D010607:Pharmacy Service, Hospital / Q000379:methods; D011482:Protective Devices; D012371:Robotics / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D003520:Cyclophosphamide
keywords: Biological safety cabinet; cyclophosphamide; cytotoxic drugs; robotic system; wipe sampling