Run: Bioreactor Operation and In-Process Monitoring SOP

The operator verifies that the batch record is approved and that the current run parameters match the authorized process instructions. Check and record the following before proceeding: - Target temperature - Target pH and allowable tolerance - Target dissolved oxygen and allowable tolerance - Agitation and aeration setpoints - Sampling frequency and required in-process tests - Alarm limits and escalation contacts If any value is missing, unclear, or outside the approved range, stop and escalate to the shift supervisor or competent person before continuing.

The operator inspects the vessel, seals, tubing, filters, probes, and agitator assembly for cleanliness, integrity, and correct installation. The operator verifies that: - The vessel is clean and assembled according to the approved setup - All ports are closed or fitted as required - No leaks, cracks, or loose fittings are present - The control system displays normal status - The data logger or electronic record system is active If a defect, leak, or contamination risk is identified, the operator stops the setup and initiates a non-conformance report.

The operator verifies calibration status and baseline performance for all critical sensors used in the run. The operator confirms that: - The pH sensor calibration is current - The dissolved oxygen sensor calibration is current - The temperature measurement device is functioning correctly - Baseline readings are stable and plausible for the prepared vessel - Any sensor drift is within the approved tolerance If a sensor is expired, unstable, or out of tolerance, the operator removes it from service and escalates before inoculation.

The operator sets the vessel to the approved pre-inoculation conditions according to the batch record. The operator adjusts only authorized parameters and verifies that: - Temperature is at the target pre-inoculation range - Agitation is at the approved starting speed - Aeration or gas flow is at the approved starting rate - pH control mode is enabled if required - Dissolved oxygen control mode is enabled if required If the system cannot reach the target condition within the allowed tolerance, the operator pauses and escalates.

The operator performs the inoculation using approved aseptic technique and the authorized inoculum volume. The operator: - Verifies the inoculum identity and lot information - Confirms the inoculum is within its allowed hold time - Transfers the inoculum aseptically into the vessel - Closes and secures all ports after transfer - Records the inoculation time in the batch record If a spill, breach, or labeling discrepancy occurs, the operator stops, contains the event, and escalates as a non-conformance.

The operator starts continuous monitoring of the critical process parameters and confirms that data are being captured. The operator verifies that the display shows: - pH trend and current value - Dissolved oxygen trend and current value - Temperature trend and current value - Agitation, aeration, and gas control status - Cell growth or biomass indicators, if available The operator confirms that data logging is active and that the timestamp is correct.

The operator checks the process at the frequency defined in the batch record and records each observation. At each monitoring point, the operator records: - pH value and trend direction - Dissolved oxygen value and trend direction - Temperature value and trend direction - Visible foam, color change, turbidity, or other growth observations - Any alarm, trend, or operator intervention The operator compares each reading to the approved tolerance and documents any corrective action taken.

The operator evaluates whether any critical parameter is outside the approved tolerance or trending toward an alarm limit.

The operator continues the run and maintains the batch record, electronic logs, and any required sample records. The operator verifies that: - Entries are complete, legible, and time-stamped - Any routine adjustments are within approved limits - No unresolved alarms remain active The operator proceeds to the next scheduled monitoring point.

The operator stops any unauthorized adjustment and escalates the deviation according to the site escalation path. The operator: - Records the observed deviation and time of occurrence - Notifies the shift supervisor or competent person - Places the process in the approved safe state if required - Opens a non-conformance or deviation record - Follows disposition instructions before resuming the run Do not resume processing until the deviation is reviewed and authorized.