Maintaining aseptic conditions in the face of unexpected events: performance qualification of a modular controlled atmosphere area dedicated to ATMPs and clinical trials

Introduction
The deployment of a modular Controlled Atmosphere Area (CAA) in the hospital in 2025 made it possible to meet the growing demand for the preparation of Advanced Therapy Medicinal Products (ATMPs) and clinical trials (CTs). Following initial and operational qualification, the performance qualification (PQ) required for sterile preparation activities was conducted in accordance with the 2023 French Good Preparation Practices (GPP) guidelines.

Objective
To demonstrate the ability of the modular CAA to meet the requirements of performance qualification.

Materials and methods
The qualification was based on four assessment criteria: (1) Microbiological air and surface monitoring under simulated operating conditions using TSA media (active air samplers and contact plates) to assess the impact of personnel on the preparation environment. (2) Particle counting and air-handling system performance measurements (performed by an external service provider) under both at-rest and operational conditions. (3) Airborne Surface Disinfection (ASD; Phileas75^®) using hydrogen peroxide (H₂O₂) diffusion was assessed using chemical indicators and biological indicators (Geobacillus stearothermophilus at 10⁴, 10⁵, and 10⁶). (4) An exploratory “Worst Case” test was performed by simulating a 12-hour shutdown of the air handling unit (AHU), followed by microbiological monitoring (air and surfaces) one hour after restart, in order to assess the safety of the CAA in the event of technical failures.

Results
Microbiological monitoring under operational conditions was fully compliant with the requirements of Common Guideline 1 (CG1) of the French GPP. Particle counts and air-handling system performance measurements confirmed that the expected specifications were met under both at-rest and operational conditions. Furthermore, the sporicidal efficacy of ASD demonstrated a 10⁶ bacterial reduction throughout all areas of the preparation room, except for one corner of the room where a 10⁵ reduction was observed. Finally, the AHU shutdown simulation (“Worst Case”) demonstrated restoration of air-handling system parameters (airflow and pressure cascade) within a few minutes. Microbiological samples collected one hour after restart—corresponding to 60 air changes in the preparation room and 20 air changes in the airlocks/pass-through—confirmed the effectiveness of the recovery process, with full compliance with the CG1 requirements of the GPP.

Conclusion and discussion
The modular CAA met the objectives of the performance qualification, with microbiological monitoring under operational conditions compliant with GPP requirements and satisfactory sporicidal efficacy of ASD. The rapid recovery of the required cleanliness class following a prolonged AHU shutdown confirms the room’s ability to ensure the safety of sterile preparations under both normal and degraded operating conditions. However, this microbiological validation should be further consolidated by particle counting during a future AHU shutdown simulation.

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