Environment Monitoring in a Cell Therapy Manufacturing Facility – 3 Year Data Analysis

Background & Aim To study the Environment Monitoring (EM) activities in a hospital-based Cell Therapy Manufacturing Facility (mainly processes islet cells and HPC(s), to ensure compliance with FACT (03/2018), ISO14644 (12/2015), validation standards and facility EM SOP. Methods, Results & Conclusion Methods Available EM data from 08/2014 to 12/2017 analyzed, including initial validation EM by vendor. EM are normally performed on a monthly basis, while some months had partial or no EM done due to facility construction, schedule conflicts, or machine error. EM includes particle count (PC), air sampling (AS), contact plate bacterial & fungal (CP). See Image 1 for routine EM locations. CR: Cleanroom; GR: Gown Room; DR: Degown Room; BSC: Biosafety Cabinet. Results In the 41 months, 37 months of particle counts, 40 months of Air Sampling, 38 months of contact plate data were analyzed. Among them, (1) One was In-Process EM, all the others were At Rest EM. The In-Process particle counts were significantly higher than those At-Rest. (2) All critical ISO 5 areas were all within expected ranges for all three EM parameters. (3) Two deviations filed due to high air sampling counts, and both passed after improving operator technique and after facility cleaning. (4) In this 3 year data, particle counts and contact plates results are trending low or stable, within expected range, while Air Sampling results had some fluctuations, see Image 2 and 3. (5) Besides the regular/routine sampling locations, several non-routine sampling locations were also sampled, which detected “mold” in Incubator, “>100 CFU” in freezer, and both repeated “0 CFU” count after equipment decontamination. See Image 3. Conclusion (1) The facility's EM program monitors particulates, microbial contamination, with proper sampling sites, frequency, investigative and corrective actions when specified limits exceeded. (2) All BSC data were satisfactory and safe for cell therapy manufacturing processes. (3) Gown Room and Degown Room were built per ISO 8, and met ISO 7 requirements. (4) More In-Process EM shall be performed to provide baseline data during manufacturing. (5) Non-routine sampling in ISO unclassified areas helps detect suspected/ at risk areas, and help improve the cleanliness of the facility.