ICH guidelines.

2. Scope

This SOP is applicable to all injectable products undergoing sterile manufacturing that require bulk filtration through validated filters prior to filling operations.

3. Responsibilities

• Production Personnel: Perform the filtration process following validated procedures.
• Quality Assurance (QA): Monitor process compliance and verify filter integrity tests.
• Engineering: Ensure availability and proper functioning of filtration equipment.
• Microbiology/QC: Conduct pre- and post-filtration bioburden and sterility checks.

4. Accountability

The Head of Manufacturing is accountable for adherence to filtration procedures and ensuring that only validated and approved equipment and filters are used. QA Head is accountable for compliance verification.

5. Procedure

5.1 Preparation and Setup

1. Review Batch Manufacturing Record (BMR) and filtration instructions.
2. Ensure cleanliness of the filtration suite as per SOP for cleanroom sanitization.
3. Verify and assemble all components required:
   • Filtration unit (pressure vessel or TFF system)
   • Validated 0.22 μm or 0.1 μm filters
   • Sanitized hoses and clamps
   • Sterile collection bags or intermediate tanks

5.2 Filter Integrity Testing (Pre-Use)

1. Conduct a bubble point or diffusive flow test using an integrity tester (e.g., Palltronic, Sartocheck).
2. Record results in the Filter Integrity Logbook (Annexure-1).
3. Ensure test passes per manufacturer’s specification before proceeding.

5.3 Filtration Process

1. Attach the filtration assembly to the product transfer line under LAF conditions.
2. Initiate filtration using peristaltic pump or compressed nitrogen with regulated pressure (typically < 1.5 bar).
3. Monitor pressure gauges for any fluctuations or signs of clogging.
4. Continue filtration until the full batch is processed.
5. Maintain unidirectional flow and avoid backpressure to prevent filter rupture.
6. Record filtration start and end time, batch number, and volume filtered.

5.4 Filter Integrity Testing (Post-Use)

1. Repeat the integrity test using the same test method.
2. Failure to pass the test requires batch rejection or thorough investigation.
3. Document all results and sign off in the BMR and QA record.

5.5 Handling of Materials and Equipment

1. Dispose of used filters in designated biohazard containers.
2. Sanitize equipment using 70% IPA before removal from sterile area.
3. Send the filtration unit for cleaning as per equipment cleaning SOP.

5.6 Documentation and Review

1. Ensure all parameters (flow rate, pressure, time) are documented in the Filtration Checklist (Annexure-2).
2. QA shall review the checklist and integrity test logs for completeness and correctness.
3. Release batch only after successful review of filtration records.

6. Abbreviations

• SOP: Standard Operating Procedure
• BMR: Batch Manufacturing Record
• IPA: Isopropyl Alcohol
• LAF: Laminar Airflow
• QA: Quality Assurance
• QC: Quality Control

7. Documents

1. Filter Integrity Logbook – Annexure-1
2. Filtration Checklist – Annexure-2
3. Batch Manufacturing Record (BMR)

8. References

• EU GMP Annex 1 – Manufacture of Sterile Medicinal Products
• ICH Q8 – Pharmaceutical Development
• USP <788> – Particulate Matter in Injections

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 Logbook

Date	Filter ID	Test Type	Pre-Use Result	Post-Use Result	Tested By
22/06/2025	FLTR-1025	Bubble Point	Pass	Pass	Sunita Reddy

Annexure-2: Filtration Checklist

Batch No.	Product	Start Time	End Time	Volume Filtered (L)	Operator
BN-4597	Ceftriaxone Injection	09:00 AM	10:30 AM	150	Rajesh Kumar

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
20/06/2022	1.0	Initial SOP	New Document	QA Head
24/06/2025	2.0	Updated to include post-use integrity testing and checklist	Annual Review	QA Head