Isolator: Does a break of containment leads always to a break of sterility ?
Service Pharmacie CHU Saint-Louis, Paris
Break of containment may occur when handling in an isolator. This incident is rare and restrictive. The most common cause is the loss of the waste basket between the isolator workstations (-50 Pa depression; 70 V/hour; V: one m3). The decision to quarantine the equipment or perform decontamination disrupts the manufacturing organization. To rationalize this decision, we searched for biological contamination.
A two-phase study was conducted:
1a) Identification of critical points: aerodynamic smoke test in empty and full isolator.
1b) Positive control with 30 minutes unhooked waste basket, air sampling every 10 minutes (3 points) and critical points identified by open tryptone soya agar plate (8 points) and change every 5 minutes, namely 48 points.
2) Simulation of the incident: Unhooking the waste basket from the waste outlet (n = 3) until the alarm appears (1 min) then closing the outlet with sampling before / after: tryptone soya agar plate (7 points), swabs (10 points) and air (1 point)) at different times, air: 1, 5 and 45 min, surfaces: 45 minutes.
Tests 1a) identified shelves as critical and showed a total lack of smoke after 5 minutes. In empty isolator, the air renewal observed was longer. The results of test 1b) made in empty isolator shows contamination for the 3 air samples and for 6/48 surface points. The simulation scenario revealed that air sample at 1 min was the only one contaminated but none of surface samples. Shelves are the first obstacle encountered by the directed air flow and identified as critical. The control 1b) confirms that the detected contamination is coherent with the aerodynamic. Thanks to strong air renewal, the study showed only the first air sample was contaminated. Following these results, the procedure have been changed: closing the waste outlet, stop manufacturing during 6 min, recovery of the activity after destroying the ongoing preparations and cleaning the working area.