Standard Operating Procedure for Resin Regeneration and Storage in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/169/2025
Supersedes	SOP/BS/169/2022
Page No.	Page 1 of 9
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define the procedure for the regeneration and storage of chromatography resins used in biosimilar manufacturing to maintain resin performance, prevent microbial growth, and ensure compliance with GMP guidelines.

2. Scope

This SOP applies to all resins used in purification steps such as affinity, ion-exchange, hydrophobic interaction, and size-exclusion chromatography, across pilot and commercial production units in biosimilar manufacturing.

3. Responsibilities

• Production: Perform resin regeneration after each cycle and ensure proper storage.
• QA: Review resin regeneration logs and approve storage status.
• Engineering: Support resin regeneration by maintaining pumps, skids, and sensor calibration.

4. Accountability

The Head of Downstream Manufacturing is accountable for ensuring all resins are regenerated and stored as per SOP before reuse or archival.

5. Procedure

5.1 Pre-Regeneration Checks

1. Ensure that the column containing resin has completed its purification or CIP run.
2. Confirm resin ID, column ID, and product batch in Annexure-1.
3. Verify the validated regeneration protocol based on resin type.

5.2 Resin Regeneration Steps

1. Protein A Resin:
   • Wash with 6 CV of 0.1 M NaOH at room temperature
   • Hold for 15 minutes contact time
   • Rinse with WFI until neutral pH
2. Ion Exchange Resin:
   • Use alternating washes of 1 M NaOH and 1 M NaCl
   • Flush with WFI to remove chemical residues
3. HIC Resin:
   • Wash with 20% ethanol followed by 0.5 M NaOH
   • Final rinse with WFI

5.3 Storage Conditions

1. Resins not used for >24 hours must be stored under appropriate conditions:
   • Protein A: 20% ethanol in WFI at 2–8°C
   • IEX: 0.1 M NaCl with 20% ethanol
2. Fill column with storage buffer until full, avoiding air bubbles.
3. Seal column ports with sanitary end caps and label with resin ID, storage date, and next due regeneration date.

5.4 Resin Storage Outside Column

1. Transfer resin to sanitized resin storage bags or vessels.
2. Ensure continuous suspension and temperature monitoring.
3. Stir gently every 7 days to maintain resin integrity.

5.5 Documentation and Verification

1. Record regeneration date, chemicals used, contact times, and observations in Annexure-2.
2. QA to verify neutralization, pH, and physical integrity before releasing resin for reuse.

6. Abbreviations

• CIP: Clean-In-Place
• IEX: Ion Exchange
• WFI: Water for Injection
• CV: Column Volume

7. Documents

1. Resin Regeneration Log – Annexure-1
2. Storage Condition Record – Annexure-2

8. References

• ICH Q7 – GMP for Active Pharmaceutical Ingredients
• WHO TRS 999 – GMP for Biologics
• OEM Resin Guidelines – Cytiva, Bio-Rad, Repligen

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Resin Regeneration Log

Date	Resin ID	Resin Type	Cleaning Agent	Contact Time	Operator
04/05/2025	RES-PA-104	Protein A	0.1 M NaOH	15 min	Ajay Verma

Annexure-2: Storage Condition Record

Resin ID	Storage Buffer	Storage Temp	Storage Date	Next Regeneration Due	QA Verified
RES-PA-104	20% EtOH in WFI	2–8°C	04/05/2025	04/06/2025	Sunita Reddy

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Added guidance for off-column resin storage	Operational feedback and QA review