Standard Operating Procedure for Resin Life Cycle Management in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/167/2025
Supersedes	SOP/BS/167/2022
Page No.	Page 1 of 11
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define the procedure for managing the complete life cycle of chromatography resins used in biosimilar manufacturing, including usage tracking, regeneration, performance monitoring, and safe disposal to ensure GMP compliance and consistent product quality.

2. Scope

This SOP applies to all types of chromatography resins (e.g., Protein A, ion exchange, hydrophobic interaction, size exclusion) used in downstream purification of biosimilar products in pilot and commercial scale facilities.

3. Responsibilities

• Production: Track resin usage, complete regeneration and storage, and maintain resin logs.
• QA: Review and approve resin performance trends and life cycle records.
• Validation: Qualify new resin lots and evaluate reuse limits based on product-specific data.

4. Accountability

The Head of Downstream Manufacturing is accountable for ensuring resin use is within approved life cycle limits and all records are maintained and reviewed for regulatory inspections.

5. Procedure

5.1 Resin Receipt and Qualification

1. Receive resin with COA and ensure label integrity and lot traceability.
2. Assign a unique Resin ID and enter into the Resin Inventory Log (Annexure-1).
3. Conduct acceptance testing as per validation protocol (e.g., binding capacity, microbial limit).

5.2 Resin Usage Tracking

1. Track resin usage batch-wise in the Resin Use Log (Annexure-2).
2. For each cycle, document:
   • Batch No.
   • Cleaning and sanitization agent used
   • Number of reuse cycles completed
   • Performance characteristics (binding capacity, pressure drop)

5.3 Regeneration and Sanitization

1. After each use, clean resin using validated CIP protocols (refer to individual resin cleaning SOPs).
2. Sanitize resin with 0.5 M NaOH for 30 min contact time or as per manufacturer’s recommendation.
3. Flush with WFI until pH neutral and store in 20% ethanol buffer at 2–8°C.

5.4 Performance Monitoring

1. At defined intervals (e.g., every 10th cycle), perform:
   • Dynamic Binding Capacity (DBC) test
   • Column pressure profile
   • Visual inspection of resin
2. Compare results against initial baseline values.
3. Document findings in the Resin Performance Evaluation Sheet (Annexure-3).

5.5 Reuse Limits and Retirement Criteria

1. Set reuse limits based on process validation (e.g., 100 cycles for Protein A).
2. Retire resin when:
   • Binding capacity drops by > 20% from initial value
   • Increased back pressure beyond spec
   • Resin discoloration or physical degradation
3. Record resin retirement in Annexure-4 and update inventory status as ‘Obsolete’.

5.6 Resin Disposal

1. Dispose of expired or damaged resin as per SOP for Hazardous Waste Disposal.
2. Label containers clearly and ensure transport to authorized waste treatment facility.

6. Abbreviations

• DBC: Dynamic Binding Capacity
• COA: Certificate of Analysis
• CIP: Clean-In-Place
• WFI: Water for Injection

7. Documents

1. Resin Inventory Log – Annexure-1
2. Resin Use Log – Annexure-2
3. Resin Performance Evaluation Sheet – Annexure-3
4. Resin Retirement Record – Annexure-4

8. References

• ICH Q9 – Quality Risk Management
• WHO TRS 999 – GMP for Biotherapeutics
• OEM Resin Use Guidelines (GE, Repligen, Cytiva)

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 Inventory Log

Resin ID	Resin Type	Lot No.	Vendor	Received Date	Status
RES-QA-101	Protein A	PA-4521	Cytiva	01/03/2025	Active

Annexure-2: Resin Use Log

Cycle No.	Batch No.	Date	Sanitization Performed	Operator
1	BS-MAB-022	04/03/2025	Yes	Ajay Verma

Annexure-3: Resin Performance Evaluation Sheet

Cycle	Binding Capacity	Pressure Drop	Observations	Result
10	92%	1.2 bar	No change	Acceptable

Annexure-4: Resin Retirement Record

Resin ID	Reason for Retirement	Retirement Date	Disposed By
RES-QA-088	Binding loss > 20%	01/05/2025	Sunita Reddy

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Included detailed resin performance metrics and disposal guidelines	Process harmonization