Run: Bioreactor Operation and In-Process Monitoring SOP

The operator verifies the batch record, product identity, vessel ID, target working volume, and approved setpoints for pH, dissolved oxygen, temperature, agitation, and aeration. The operator records any pre-run constraints, hold points, or escalation thresholds in the process log.

The operator verifies that the vessel is clean, assembled, sterilized or otherwise released for use, and free from visible damage or leaks. The operator confirms that the pH probe, dissolved oxygen sensor, temperature control loop, agitation system, and gas supply are connected and in ready status.

The operator checks the calibration status, last calibration date, and any required zero or span checks for the pH and dissolved oxygen sensors. The operator verifies that temperature indication matches the qualified reference or control display within the site tolerance.

The operator sets the vessel to the approved pre-inoculation temperature, agitation, and gas flow conditions. The operator waits until the process display indicates stable conditions within the defined tolerance before inoculation.

The operator transfers the approved inoculum into the bioreactor using the validated sterile connection method. The operator records inoculum lot number, volume, transfer time, and any observed anomalies in the batch record.

The operator monitors the immediate post-inoculation readings and confirms that the process remains within the approved tolerance band. The operator documents the initial response and notes any unexpected drift, foaming, or alarm conditions.

The operator records pH, dissolved oxygen, temperature, agitation, aeration, and any required cell growth indicators at the defined monitoring interval. The operator compares each reading to the approved tolerance and records the trend direction, including any gradual drift or recovery after control action.

The operator compares the latest readings against the approved acceptance criteria and determines whether the run can continue under normal monitoring or requires escalation.

The operator continues the run under the approved control strategy and documents the completed monitoring interval in the batch record. The operator repeats monitoring at the required frequency until the next scheduled check or process milestone.

The operator stops routine adjustments that are outside authorized limits, records the deviation, and notifies the shift supervisor or competent person. The operator documents the observed value, time of occurrence, corrective action taken, and any impact assessment. The operator follows the site non-conformance and escalation procedure before resuming the run.