to all lyophilizers used for sterile injectable manufacturing in the facility. It covers calibration activities for vacuum sensors, temperature probes, pressure transducers, and other critical measurement systems.

3. Responsibilities

• Calibration Technician: Execute calibration as per schedule and approved protocol.
• Engineering Supervisor: Review calibration results and approve calibration certificates.
• QA Officer: Verify calibration documentation and ensure equipment is within tolerance before use.

4. Accountability

The Head of Engineering is accountable for ensuring lyophilizers are calibrated as per schedule and in compliance with regulatory and GMP requirements.

5. Procedure

5.1 Calibration Schedule

1. Prepare an annual calibration plan for all lyophilizers and associated instruments.
2. Maintain a log of due dates and calibration frequency (quarterly, semi-annually, or annually as applicable).

5.2 Preparation Before Calibration

1. Ensure lyophilizer is in standby mode and disconnected from production schedule.
2. Clean chamber and ensure no product residues remain.
3. Notify QA and obtain equipment release before initiating calibration.

5.3 Calibration of Temperature Sensors

1. Use a calibrated reference temperature probe traceable to national/international standards.
2. Place reference and installed sensors in identical conditions across various shelf positions.
3. Record readings at set points (e.g., -40°C, 0°C, +20°C).
4. Ensure deviation is within ±1°C; otherwise, adjust or replace sensor.

5.4 Calibration of Vacuum Sensors

1. Use a calibrated digital vacuum gauge as reference.
2. Connect the gauge to the vacuum line through a standard port.
3. Apply vacuum and compare readings at -100 mbar, -500 mbar, and -800 mbar.
4. Acceptable deviation is ±3% of reading.

5.5 Calibration of Pressure Transducers

1. Connect pressure source and reference manometer to the transducer circuit.
2. Calibrate at multiple set points (e.g., 0.5, 1.0, and 1.5 bar).
3. Verify linearity and document calibration curve.

5.6 Calibration of Data Logger/Controller System

1. Verify that display values match those recorded by calibrated sensors.
2. Check time synchronization with system clock.
3. Validate alarm triggering accuracy for deviations.

5.7 Documentation

1. Complete Calibration Report (Annexure-1) with before and after values.
2. Affix calibration status label with date and due date on the lyophilizer panel.
3. Scan and archive documents in the calibration file and electronic record system.

5.8 Handling of Out-of-Tolerance (OOT) Results

1. If any reading is out of tolerance:
   • Inform QA and Engineering immediately.
   • Quarantine the equipment.
   • Initiate investigation and corrective action.
   • Assess impact on batches processed since last calibration.

5.9 Requalification Requirements

1. If critical instruments are replaced or adjusted significantly, perform Operational Qualification (OQ) before resuming production.

5.10 Review and Training

1. Calibration team must be trained on lyophilizer model, tools, and SOP annually.
2. QA shall review calibration compliance monthly.

6. Abbreviations

• SOP: Standard Operating Procedure
• QA: Quality Assurance
• OQ: Operational Qualification
• OOT: Out of Tolerance
• cGMP: current Good Manufacturing Practices

7. Documents

1. Calibration Report – Annexure-1
2. Calibration Status Label – Annexure-2
3. Instrument Master Calibration Log – Annexure-3

8. References

• WHO Technical Report Series 961 Annex 6 – GMP for sterile pharmaceutical products
• 21 CFR Part 211.68 – Automatic, mechanical, and electronic equipment
• ICH Q9 – Quality Risk Management

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Manufacturing Executive	QA Executive	Head QA
Department	Production	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Calibration Report

Instrument	Location	Set Point	Observed	Status	Technician
Temp Probe	Shelf 1	20°C	19.8°C	Pass	Ramesh Lal

Annexure-2: Calibration Status Label

Equipment ID	Date	Next Due	Technician	Status
LYO-06	22/06/2025	22/06/2026	Sunita Mehra	Calibrated

Annexure-3: Instrument Master Calibration Log

Instrument ID	Type	Frequency	Last Calibrated	Next Due
LYO-TMP-01	Temperature Sensor	Yearly	22/06/2025	22/06/2026

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
01/04/2022	1.0	Initial release	New equipment	QA Head
24/06/2025	2.0	Updated annexures and calibration frequencies	Scheduled review	QA Head