Bioreactor Operation and In-Process Monitoring SOP

Standard operating procedure for inoculating a production bioreactor and monitoring critical process parameters including pH, dissolved oxygen, temperature, and cell growth throughout the run.

Steps

• Verify the batch record and run setpoints
  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.
• Inspect the bioreactor and confirm readiness
  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.
• Confirm sensor calibration and baseline readings
  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.
• Set the bioreactor to pre-inoculation conditions
  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.
• Inoculate the bioreactor aseptically
  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.
• Verify initial process response after inoculation
  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.
• Monitor pH, dissolved oxygen, temperature, and growth trend
  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.
• Decide whether process values remain within tolerance
  The operator compares the latest readings against the approved acceptance criteria and determines whether the run can continue under normal monitoring or requires escalation.
• Continue routine monitoring and document the interval
  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.
• Escalate the deviation and place the run under review
  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.