Standard Operating Procedure for Water for Injection (WFI) Systems Usage in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/127/2025
Supersedes	SOP/BS/127/2022
Page No.	Page 1 of 12
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To establish a procedure for the usage, monitoring, and documentation of Water for Injection (WFI) in biosimilar manufacturing processes, ensuring compliance with GMP, pharmacopeial, and microbiological standards.

2. Scope

This SOP applies to all activities involving the use of WFI from generation, storage, distribution, and dispensing points in the biosimilar facility’s upstream and downstream areas.

3. Responsibilities

• Engineering: Operate and maintain the WFI generation and distribution system. Perform sanitization.
• Production: Use WFI as per batch requirement and record usage.
• QC: Perform sampling and testing of WFI at designated user points.
• QA: Review usage logs and test results. Release WFI lines after sanitization.

4. Accountability

The Head of Engineering is accountable for ensuring uninterrupted WFI supply and system compliance. The Head of QA ensures release of sanitized lines and compliance to specifications.

5. Procedure

5.1 WFI Generation and Storage

1. Generate WFI through multi-effect distillation system or vapor compression distiller.
2. Store WFI in jacketed, temperature-controlled storage tanks (≥80°C).
3. Record system temperature, pressure, and conductivity continuously (Annexure-1).

5.2 WFI Distribution and Use

1. WFI to be used only from approved user points with validated loop design.
2. Before each use:
   • Flush for 30–60 seconds
   • Check point-of-use temperature (must be ≥70°C for hot loops or ≤25°C for cold loops)
3. Use sterile hoses/tubing, and never reuse unless validated.
4. Document WFI usage in Annexure-2: WFI Usage Logbook.

5.3 Microbiological and Chemical Testing

1. Perform sampling from user points as per validation matrix:
   • Daily: Conductivity, TOC
   • Weekly: Microbial count
   • Monthly: Endotoxin testing
2. QC to record results in Annexure-3: WFI Quality Summary Log.
3. Out-of-specification results to be managed as per deviation handling SOP.

5.4 Sanitization and Maintenance

1. Perform periodic heat sanitization or chemical sanitization of storage and distribution system.
2. Record details including temperature, duration, and outcome in Annexure-4.
3. QA to verify successful sanitization before releasing the line.

6. Abbreviations

• WFI: Water for Injection
• TOC: Total Organic Carbon
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. WFI Generation and Monitoring Log – Annexure-1
2. WFI Usage Logbook – Annexure-2
3. WFI Quality Summary Log – Annexure-3
4. Sanitization Record – Annexure-4

8. References

• USP & EP Specifications for Water for Injection
• WHO TRS 970 – Annex 2
• ISPE Baseline Guide: Water and Steam Systems

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: WFI Generation and Monitoring Log

Date	Time	Temp (°C)	Conductivity	Pressure	Remarks
04/05/2025	10:00	81.5	0.6 µS/cm	1.8 bar	OK

Annexure-2: WFI Usage Logbook

Date	Location	Volume Used	Flushed (Y/N)	Used By
04/05/2025	Media Prep	15 L	Y	Ajay Verma

Annexure-3: WFI Quality Summary Log

Date	Point ID	Conductivity	TOC	Microbial	Endotoxin
03/05/2025	WFI-POU-03	0.7	350 ppb	0 CFU/mL	0.01 EU/mL

Annexure-4: Sanitization Record

Date	Type	Temp/Agent	Duration	Performed By	QA Review
01/05/2025	Heat	85°C	1 hr	Sunita Reddy	Approved

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Clarified daily TOC/conductivity and added sanitization annexure	GMP compliance