with cGMP requirements.

2. Scope

This SOP applies to all personnel involved in the operation, monitoring, and cleaning of lyophilizers in the sterile injectable manufacturing facility.

3. Responsibilities

• Lyophilizer Operator: Performs setup, loading, unloading, and monitoring of the lyophilization process.
• Production Supervisor: Reviews lyophilizer readiness and batch documentation.
• QA Officer: Performs in-process checks, reviews cycle parameters, and verifies documentation.

4. Accountability

The Head of Production is accountable for ensuring that only trained personnel operate the lyophilizer and that all procedures are followed as per validated protocols.

5. Procedure

5.1 Pre-Operation Checks

1. Verify that the lyophilizer is labeled “CLEANED” and has a valid status label.
2. Ensure the chamber and door gaskets are visually clean and free from residues.
3. Check the integrity of the condenser coils and vacuum lines.
4. Confirm readiness of the associated utilities: compressed air, vacuum, and chilled water.
5. Record checks in the Lyophilizer Pre-Use Checklist (Annexure-1).

5.2 Loading of Product

1. Ensure that filled and partially stoppered vials are loaded under LAF conditions into pre-sterilized lyophilizer trays.
2. Load trays into lyophilizer shelves without disturbing stopper positions.
3. Ensure even spacing and avoid overloading.

5.3 Cycle Setup and Initiation

1. Select the validated lyophilization cycle from the HMI/PLC interface.
2. Verify shelf temperature set-points and vacuum pressure ranges as per BMR.
3. Seal the lyophilizer door and initiate the cycle.
4. Record start time, cycle ID, and operator details in Lyophilization Log (Annexure-2).

5.4 Primary and Secondary Drying

1. Monitor the product and shelf temperature regularly during drying phases.
2. Document chamber pressure, condenser temperature, and alarms if any.
3. Ensure shelf temperature transitions and vacuum are within validated range.

5.5 Unloading of Product

1. After cycle completion, break vacuum with sterile filtered air.
2. Check dryness of samples via weight comparison or moisture analysis.
3. Remove vials under LAF, seal with aluminum caps, and transfer to further inspection.

5.6 Post-Operation Activities

1. Initiate lyophilizer cleaning as per SOP for Equipment Cleaning.
2. Complete Lyophilizer Operation Log and Cleaning Record (Annexure-3).
3. Submit all records to QA for review and archival.

6. Abbreviations

• SOP: Standard Operating Procedure
• LAF: Laminar Airflow
• BMR: Batch Manufacturing Record
• PLC: Programmable Logic Controller
• QA: Quality Assurance

7. Documents

1. Lyophilizer Pre-Use Checklist – Annexure-1
2. Lyophilization Operation Log – Annexure-2
3. Lyophilizer Cleaning Record – Annexure-3

8. References

• WHO GMP Guidelines for Sterile Pharmaceuticals
• EU GMP Annex 1 – Manufacture of Sterile Products
• ICH Q8 – Pharmaceutical Development

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: Lyophilizer Pre-Use Checklist

Date	Machine ID	Gasket OK	Vacuum Line Intact	Checked By
18/06/2025	LYO-002	Yes	Yes	Rajesh Kumar

Annexure-2: Lyophilization Operation Log

Batch No.	Cycle ID	Start Time	End Time	Operator
LYO/IV/2025/021	LYO-5-25	08:30	20:00	Sunita Reddy

Annexure-3: Lyophilizer Cleaning Record

Date	Cleaned By	Cleaning Method	Remarks
18/06/2025	Ajay Verma	70% IPA + WFI Rinse	Completed

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
10/01/2022	1.0	Initial Issue	New SOP	QA Head
18/06/2025	2.0	Updated procedure and annexures	Periodic Review	QA Head