Standard Operating Procedure for Resin Performance Qualification in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/199/2025
Supersedes	SOP/BS/199/2022
Page No.	Page 1 of 10
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To establish a validated and GMP-compliant procedure for qualifying the performance of chromatography resins used in biosimilar purification processes, including assessment of binding capacity, leakage, pressure-flow characteristics, and resin longevity.

2. Scope

This SOP applies to all resins used in protein A, ion-exchange (IEX), hydrophobic interaction chromatography (HIC), and size exclusion chromatography (SEC) operations in downstream processing of biosimilars.

3. Responsibilities

• Process Development: Define performance specifications and sampling plan.
• Production: Execute purification runs and collect samples for analysis.
• QC: Perform analytical testing of collected fractions (titer, HCP, DNA, leakage).
• QA: Review qualification data and approve resin use beyond initial lifecycle.

4. Accountability

The Head of Manufacturing and Head of Quality Control are accountable for the implementation and lifecycle qualification of chromatography resins in accordance with GMP standards.

5. Procedure

5.1 Resin Selection and Documentation

1. Ensure all chromatography resins are purchased from approved vendors with CoA and MSDS.
2. Record resin lot number, batch number, manufacturer, and expiry in Annexure-1.

5.2 Initial Qualification (Baseline Run)

1. Pack the chromatography column as per validated protocol.
2. Perform a standard purification cycle using qualified bulk material.
3. Measure and record:
   • Dynamic binding capacity (DBC) at 10% breakthrough
   • Recovery yield (%)
   • Pressure vs. flow rate profile
   • Leakage of ligand or protein A (Annexure-2)

5.3 Periodic Qualification (Usage-Based)

1. At defined intervals (e.g., every 10 cycles), repeat DBC and leakage testing.
2. Monitor changes in pressure-flow behavior and compare with baseline.
3. Document results in Resin Qualification Log (Annexure-3).

5.4 Acceptance Criteria

1. DBC should not decrease by more than 20% from initial value.
2. Ligand leakage (e.g., protein A) must remain within qualified limits (e.g., <10 ppm).
3. Flow rate at standard pressure must not fall below 80% of baseline.

5.5 Resin Cleaning and Storage

1. Clean resin using vendor-recommended protocol (e.g., 0.1 M NaOH for Protein A).
2. Store resin in validated storage buffer at 2–8°C, protected from light.

5.6 Requalification or Discontinuation

1. If any parameter exceeds acceptance criteria, perform root cause analysis (Annexure-4).
2. Resin may be:
   • Requalified after additional cleaning and retesting
   • Discarded if unfit for further use
3. Update resin inventory and lifecycle usage records.

6. Abbreviations

• DBC: Dynamic Binding Capacity
• HCP: Host Cell Protein
• CoA: Certificate of Analysis
• MSDS: Material Safety Data Sheet

7. Documents

1. Resin Receipt and Tracking Log – Annexure-1
2. Baseline Qualification Report – Annexure-2
3. Resin Performance Log – Annexure-3
4. Root Cause and Requalification Record – Annexure-4

8. References

• ICH Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
• PDA TR No. 60 – Process Validation: A Lifecycle Approach
• Resin vendor product monographs and technical bulletins

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 Receipt and Tracking Log

Resin Name	Lot No.	Manufacturer	Qty (L)	Received On	Expiry
Protein A MabSelect	PA23456	Cytiva	10	01/04/2025	01/04/2028

Annexure-2: Baseline Qualification Report

Date	Column ID	DBC (mg/mL)	Yield (%)	Pressure @ Flow Rate	Leakage (ppm)
02/04/2025	CH-101	38	92	1.2 bar @ 300 cm/h	5.2

Annexure-3: Resin Performance Log

Cycle No.	Date	DBC	Yield	Leakage	Status
20	20/04/2025	36	91%	6.1 ppm	Pass

Annexure-4: Root Cause and Requalification Record

Date	Resin	Issue	Root Cause	Corrective Action	Disposition
28/04/2025	Protein A	Leakage >10 ppm	Inadequate cleaning	Repeated CIP with NaOH	Requalified

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Included resin leakage and lifecycle limits	GMP enhancement