Standard Operating Procedure for Filtration Process in Sterile Injections

Department	Sterile Injectable Manufacturing
SOP No.	SOP/SIM/027/2025
Supersedes	SOP/SIM/027/2022
Page No.	Page 1 of 15
Issue Date	18/06/2025
Effective Date	20/06/2025
Review Date	18/06/2026

1. Purpose

This SOP describes the procedure for performing sterile filtration during the manufacturing of injectable drug products. It ensures removal of bioburden and particulates prior to aseptic filling in compliance with GMP and regulatory requirements.

2. Scope

This procedure is applicable to all sterile injectable formulations requiring sterile filtration using 0.22 µm or equivalent validated membrane filters in the Sterile Injectable Manufacturing facility.

3. Responsibilities

• Manufacturing Operator: Executes filtration and records data as per BMR.
• Supervisor: Verifies setup, parameters, and signs off on in-process checks.
• QA Executive: Provides line clearance, performs periodic checks, and ensures compliance with aseptic practices.
• Engineering Team: Assists in setup, calibration, and maintenance of filtration equipment.

4. Accountability

Head – Production is accountable for execution. Head – QA is accountable for final approval and compliance oversight.

5. Procedure

5.1 Pre-Filtration Preparation

1. Verify cleaning and sterilization status of filtration assembly and bulk solution tank.
2. Check batch-specific BMR for filter type, number, and validation status.
3. Ensure environmental parameters in filtration area meet Grade B or better classification.

5.2 Filter Assembly Setup

1. Use sterile membrane filters (typically 0.22 µm) validated for the product.
2. Attach filters aseptically under LAF hood using pre-sterilized tubing and clamps.
3. Ensure all connections are tight and leak-free.

5.3 Filtration Execution

1. Transfer the prepared bulk solution to the sterile filtration vessel.
2. Initiate filtration by gravity or pressure-driven setup as defined in the BMR.
3. Monitor differential pressure across the filter and maintain within defined limits (e.g., <2.5 bar).
4. Ensure continuous flow without interruption or contamination risk.

5.4 Filter Integrity Testing

1. Perform pre-use bubble point test or diffusive flow test on sterilized filters using validated equipment.
2. Document filter serial number, lot, and test result in Annexure-1.
3. Repeat integrity test post-filtration and ensure pass status.

5.5 Post-Filtration Activities

1. Label the sterile filtered solution container as “Sterile Bulk”.
2. Transfer to aseptic filling line under QA supervision.
3. Clean filtration setup as per cleaning SOP and record in Annexure-2.

6. Abbreviations

• SOP: Standard Operating Procedure
• BMR: Batch Manufacturing Record
• LAF: Laminar Air Flow
• QA: Quality Assurance
• µm: Micron

7. Documents

1. Filter Integrity Record – Annexure-1
2. Filtration Setup and Cleaning Record – Annexure-2
3. Environmental Monitoring Sheet – Annexure-3

8. References

• WHO TRS 961, Annex 6 – GMP for Sterile Pharmaceuticals
• EU GMP Annex 1
• 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: Filter Integrity Record

Filter ID	Lot No.	Pre-Test Result	Post-Test Result	Status	Checked By
FLT-112	F01234	Pass	Pass	Accepted	Rahul Sharma

Annexure-2: Filtration Setup and Cleaning Record

Date	Batch No.	Setup Verified By	Cleaning Done By	Remarks
18/06/2025	IVF2025-07	Priya Verma	Kamal Yadav	Setup completed and cleaned

Annexure-3: Environmental Monitoring Sheet

Area	Temperature (°C)	RH (%)	Differential Pressure (Pa)	Monitored By
Filtration Room	22	45	15	Sunita Iyer

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
15/03/2022	1.0	Initial Release	Baseline SOP	QA Head
18/06/2025	2.0	Added new annexures and clarified filter validation steps	Annual Review	QA Head