current Good Manufacturing Practices (cGMP), WHO guidelines, and ICH standards.

2. Scope

This SOP applies to the aseptic preparation, filtration, filling, sealing, and inspection of liquid sterile injectable formulations into prefilled syringes within classified cleanroom environments.

3. Responsibilities

• Manufacturing Operator: Performs all manufacturing steps in accordance with the BMR.
• Line Supervisor: Supervises operations and ensures adherence to aseptic techniques.
• QA Personnel: Monitors critical steps and authorizes batch progression through key checkpoints.
• Engineering Department: Ensures equipment qualification, calibration, and availability.
• QC Department: Conducts in-process and final product sampling and testing.

4. Accountability

The Head of Production is accountable for execution of the procedure. The Head of Quality Assurance is accountable for compliance and batch release.

5. Procedure

5.1 Pre-Manufacturing Checks

1. Ensure availability of approved Batch Manufacturing Record (BMR) and line clearance from QA (Annexure-1).
2. Verify readiness of sterile compounding and filling area (Grade B and A zones).
3. Confirm environmental monitoring, HVAC differential pressure, and temperature/humidity parameters are within limits.

5.2 Preparation of Bulk Solution

1. Dispense raw materials as per the master formula using calibrated balances in a controlled dispensing booth.
2. Transfer raw materials to a sterile manufacturing vessel fitted with agitator.
3. Dissolve API and excipients using WFI. Maintain pH and temperature as defined in the BMR.
4. Conduct pre-filtration using 5.0 µm filter to remove particulate matter.

5.3 Sterile Filtration

1. Filter the solution using validated 0.22 µm hydrophilic membrane filters.
2. Perform pre- and post-use filter integrity tests (bubble point or diffusive flow) as per Annexure-2.
3. Record all data including pressure and temperature during filtration.

5.4 Aseptic Filling Process

1. Ensure prefilled syringe filling equipment is cleaned, sterilized, and assembled under LAF (Annexure-3).
2. Load sterile syringes, plungers, and caps aseptically into the filling machine.
3. Fill defined volumes of sterile solution into prefilled syringes using peristaltic or piston pumps.
4. Insert plungers under Grade A environment and cap the syringes.

5.5 In-Process Controls

1. Conduct IPC tests: fill volume, particulate matter, appearance, and pH at defined intervals (Annexure-4).
2. Perform 100% visual inspection post-filling to reject defective units (Annexure-5).
3. Label inspected syringes with status tags and transfer to quarantine storage.

5.6 Post-Manufacturing Activities

1. Clean equipment and discard waste material as per disposal SOPs.
2. Compile BMR and submit to QA for review.
3. Initiate sample collection for QC release testing.

6. Abbreviations

• SOP: Standard Operating Procedure
• API: Active Pharmaceutical Ingredient
• BMR: Batch Manufacturing Record
• PFS: Prefilled Syringe
• IPC: In-Process Control
• WFI: Water for Injection

7. Documents

1. Line Clearance Checklist – Annexure-1
2. Filter Integrity Log – Annexure-2
3. Equipment Sterilization Record – Annexure-3
4. In-Process Control Sheet – Annexure-4
5. Visual Inspection Record – Annexure-5

8. References

• WHO Technical Report Series 961 – Annex 6
• EU GMP Annex 1: Manufacture of Sterile Medicinal Products
• ICH Q8, Q9, Q10 Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Priya Nair	Ankit Sharma	Dr. Meera Joshi
Designation	Manufacturing Executive	QA Executive	Head QA
Department	Production	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Line Clearance Checklist

Area	Checked By	Date	Status
Filling Zone	Sunita Reddy	17/06/2025	Clear

Annexure-2: Filter Integrity Log

Filter ID	Type	Pre-Test	Post-Test	Result
FLR-992	0.22 µm	Pass	Pass	Accepted

Annexure-3: Equipment Sterilization Record

Equipment	Cycle No.	Temp	Duration	Done By
Filling Machine	STM-12	121°C	30 min	Rakesh Iyer

Annexure-4: In-Process Control Sheet

Time	Parameter	Result	Limit	Checked By
11:00 AM	pH	6.7	6.5–7.0	Alok Patel

Annexure-5: Visual Inspection Record

Syringe No.	Clarity	Particles	Seal	Disposition
001122	Clear	None	OK	Accepted

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
01/03/2022	1.0	Initial Issue	Baseline SOP	QA Head
18/06/2025	2.0	Updated filtration and inspection procedures	Periodic Review	QA Head