applies to all personnel involved in the operation of sterile injectable manufacturing equipment, including vial washing machines, filling lines, lyophilizers, sealing stations, and packaging machinery within the classified cleanroom areas.

3. Responsibilities

• Machine Operators: Ensure GMP practices are followed during setup, operation, and shutdown of equipment.
• Supervisors: Verify operator compliance, perform routine checks, and escalate non-compliance.
• QA Personnel: Perform periodic audits and approve batch and cleaning records.

4. Accountability

The Head of Production is accountable for enforcing GMP standards. The Head of Quality Assurance is accountable for ensuring audits and compliance reviews are conducted and documented.

5. Procedure

5.1 GMP Requirements for Machine Operation

1. Ensure machine area is classified and meets environmental conditions as per batch requirement (Grade A/B/C).
2. Use cleanroom garments and PPE as per gowning SOP before operating any machine.
3. Pre-inspect machines for cleanliness, absence of contaminants, and verify completion of cleaning and maintenance logs.

5.2 Equipment Setup and Line Clearance

1. Perform line clearance using the Line Clearance Checklist (Annexure-1).
2. Ensure all previous product remnants, documents, and labels are removed from the area.
3. QA must verify and sign off the line clearance before production start.

5.3 Equipment Operation and Monitoring

1. Operate machines as per respective machine SOPs and validated parameters.
2. Record operational parameters such as speed, temperature, filling volume, and vacuum levels in the Machine Operation Log (Annexure-2).
3. Report any abnormal sound, fluctuation, or malfunction to the supervisor immediately.

5.4 Equipment Cleaning and Sanitization

1. Clean machines before and after each batch, or as per defined frequency.
2. Use validated cleaning agents only.
3. Record cleaning activities in the Equipment Cleaning Log (Annexure-3).

5.5 Preventive Maintenance and Calibration

1. Conduct preventive maintenance as per the PM schedule.
2. Ensure all critical instruments (temperature gauges, timers, sensors) are calibrated and not expired.
3. Attach calibration sticker on each calibrated component.

5.6 Documentation Practices

1. Fill all logbooks in indelible ink. Do not leave blanks.
2. Correct errors by striking a single line, signing, and dating.
3. Follow ALCOA+ principles (Attributable, Legible, Contemporaneous, Original, Accurate).

5.7 GMP Non-Compliance Handling

1. Any observed non-compliance must be documented in a Deviation Report (Annexure-4).
2. Initiate investigation and risk assessment with QA support.
3. Implement CAPA and monitor effectiveness over time.

5.8 Training Requirements

1. All machine operators must be trained annually on GMP principles and this SOP.
2. Training attendance and evaluation must be recorded in the Training Record Sheet (Annexure-5).

6. Abbreviations

• GMP: Good Manufacturing Practice
• QA: Quality Assurance
• PM: Preventive Maintenance
• SOP: Standard Operating Procedure
• CAPA: Corrective and Preventive Action

7. Documents

1. Line Clearance Checklist – Annexure-1
2. Machine Operation Log – Annexure-2
3. Equipment Cleaning Log – Annexure-3
4. Deviation Report – Annexure-4
5. Training Record Sheet – Annexure-5

8. References

• 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals
• WHO TRS 961 Annex 6 – GMP for Sterile Pharmaceutical Products
• EU GMP Guidelines Annex 1 (2022 Revision)

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: Line Clearance Checklist

Item	Status	Remarks	Checked By
Previous labels removed	Yes	NA	Sunil Sharma

Annexure-2: Machine Operation Log

Date	Machine	Parameter	Value	Operator
24/06/2025	Filler-01	Speed	180 bpm	Ravi Mehra

Annexure-3: Equipment Cleaning Log

Date	Machine	Cleaning Type	Performed By	Verified By
24/06/2025	Vial Sealer	Post-batch	Asha Patel	QA Officer

Annexure-4: Deviation Report

Date	Deviation	Root Cause	CAPA	Closure Date
22/06/2025	Wrong speed setting	Operator error	Retraining	23/06/2025

Annexure-5: Training Record Sheet

Employee Name	Date	Trainer	Topic	Remarks
Manoj Nair	15/06/2025	QA Manager	GMP for Machine Use	Passed

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial Release	New SOP	QA Head
24/06/2025	2.0	Incorporated Annexures and GMP audit clauses	Annual Review	QA Head