Standard Operating Procedure for Verification of Compressed Air Quality in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/124/2025
Supersedes	SOP/BS/124/2022
Page No.	Page 1 of 11
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To establish a standardized method for verifying the quality of compressed air used in upstream and downstream biosimilar manufacturing operations to ensure compliance with GMP and ISO 8573 air purity standards.

2. Scope

This SOP applies to all compressed air lines used in bioreactors, sampling ports, filter housings, cleaning operations, and product-contact zones in biosimilar production units.

3. Responsibilities

• Engineering: Maintain compressors, dryers, and filtration units. Support sampling activities.
• QC Microbiology: Perform air quality testing and maintain records.
• QA: Review results and ensure air meets regulatory acceptance limits before batch use.

4. Accountability

The Head of Quality Control is accountable for ensuring that compressed air used in manufacturing meets validated microbial, particulate, moisture, and oil vapor specifications.

5. Procedure

5.1 Sampling Frequency

1. Perform compressed air quality testing at all critical use points:
   • New Installations: Before use
   • Routine Monitoring: Quarterly
   • After Maintenance: Immediately

5.2 Sampling Setup

1. Use a three-way valve and validated air sampler (Annexure-1: Sampling Setup Checklist).
2. Allow a 30-second purge before collecting samples to eliminate stagnant air.
3. Label sample ports with unique ID (e.g., CA-BR-01, CA-TK-05).

5.3 Parameters and Acceptance Criteria

1. Test for:
   • Microbial Load: <1 CFU/m³
   • Particulate Matter: ≤ ISO 8573-1 Class 5
   • Oil Vapor: <0.01 mg/m³
   • Dew Point: ≤ -40°C (Class 2)
2. Document test methods and results in Annexure-2.

5.4 Action for Out-of-Specification (OOS) Results

1. Immediately report to QA and quarantine affected systems.
2. Repeat sampling after line purge and filter replacement.
3. Investigate root cause using Annexure-3: OOS Investigation Form.

5.5 Documentation

1. Maintain compressed air quality records in controlled QC files for a minimum of 5 years.
2. Attach reports to corresponding batch folders for traceability.

6. Abbreviations

• CFU: Colony Forming Units
• OOS: Out of Specification
• QC: Quality Control
• GMP: Good Manufacturing Practice

7. Documents

1. Sampling Setup Checklist – Annexure-1
2. Compressed Air Quality Report – Annexure-2
3. OOS Investigation Form – Annexure-3

8. References

• ISO 8573-1: Compressed Air Purity Classes
• WHO TRS 1019 – GMP for Biological Products
• EU GMP Annex 1 – Manufacture of Sterile Medicinal Products

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Sampling Setup Checklist

Step	Status	Remarks
Sampler Calibrated	Yes	Valid till 12/2025
Port Purged	Yes	30 seconds

Annexure-2: Compressed Air Quality Report

Date	Location ID	Microbial	Particles	Oil	Dew Point	Tested By
04/05/2025	CA-BR-01	0 CFU	Class 5	0.005 mg/m³	-42°C	Ajay Verma

Annexure-3: OOS Investigation Form

Date	OOS Parameter	Initial Value	Investigation Summary	Corrective Action
01/05/2025	Oil	0.02 mg/m³	Filter breach	Filter replaced

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Included ISO 8573 compliance parameters and expanded scope	Annual GMP review