Maintaining Quality in Stem Cell Products: Stem Cell Process Monitoring (Series Part 4 of 4)
Routine cleanroom, clean air devices, and personnel monitoring should be performed during operation throughout all critical stages. Ideally, monitoring should capture all interventions, transient events and system deterioration. The type of contamination being monitoring is either total particle (non-viable) or viable.
Requirements for All Types of Monitoring
The locations, frequency, volume, and duration of monitoring should be determined based on the risk assessment and the results obtained during the qualification. Appropriate alert and action limits are found for both viable and non-viable monitoring, and if they are exceeded, action limits are exceeded, operating procedures should document the requirement of a root-cause investigation and corrective and preventative action (CAPA) guidelines where appropriate.
Total Particle (Non-Viable) Monitoring
Total particle counts are comprised of all types of particulate matter, which can include viable particles. In Grade A areas, total particle monitoring should occur for the full duration of critical processing, including equipment assembly. Grade A areas should be monitored continuously and with suitable sample size (1 cubic foot or 28.3 liters per minute). If alert limits are exceeded, alarms should trigger. Grade B areas should also be monitored for the entire duration of the critical process, including equipment assembly (aseptic setup) and filling operations, though these areas may have decreased sample frequency5.
Total Particle Monitoring Solution: Airnet® II Air Particle Sensor
Viable counts consist of bacteria, molds, spores and yeast that is later incubated for enumeration and speciation. Where aseptic operations are performed, microbiological monitoring should be frequent and use a combination of methods such as settle plates, volumetric air, glove print, and surface sampling (e.g., swabs and contact plates). Monitoring subjects should include personnel at periodic intervals during the process, such as after critical interventions and after leaving Grade A or B areas. For microorganisms detected in Grade A or B, they must be identified to species level and their impact on product quality and state of control evaluated for each batch implicated1.
Viable Monitoring Solution: BioCapt® Single-Use Impactor
An environmental monitoring program is a core component to the overall contamination control strategy, which is defined by the manufacturer using a risk assessment of the entire process. Monitoring procedures should define the approach to trends, with reference to the following factors:
- Frequency of action or alert limits
- Consecutive alerts
- Regular but isolated alerts with a possible root cause. For example, alerts/excursions that follow planned operations.
- Changes in flora type and frequency it is seen