Standard Operating Procedure for Cold-Chain Handling and Transfer of Purified Bulk in Biosimilar Manufacturing
| Department | Biosimilars |
|---|---|
| SOP No. | SOP/BS/192/2025 |
| Supersedes | SOP/BS/192/2022 |
| Page No. | Page 1 of 9 |
| Issue Date | 04/05/2025 |
| Effective Date | 06/05/2025 |
| Review Date | 04/05/2026 |
1. Purpose
To establish a validated, GMP-compliant procedure for handling and transferring biosimilar purified bulk drug substance (BDS) under cold-chain conditions to ensure product integrity during internal movement or dispatch to fill-finish facilities.
2. Scope
This SOP applies to all biosimilar purified bulk lots that require storage and transfer at refrigerated (2–8°C) or frozen (≤ –20°C) temperatures during transit between manufacturing, storage, and formulation areas.
3. Responsibilities
- Production: Prepare and hand over purified bulk containers for cold-chain transfer.
- Warehouse/Logistics: Validate cold chain packaging, ensure calibrated temperature monitoring devices, and maintain documentation.
- QA: Approve readiness of consignment and verify records before dispatch.
4. Accountability
The Head of Supply Chain and Head of Quality Assurance are accountable for ensuring cold-chain processes maintain temperature specifications and comply with GMP requirements.
5. Procedure
5.1 Pre-Transfer Preparation
- Verify bulk product has passed all applicable in-process QC tests and QA release.
- Confirm labeling on containers includes product ID, batch number, storage condition (e.g., 2–8°C), and status (Released).
- Select pre-qualified cold boxes, gel packs, or validated passive shippers capable of maintaining temperature for the expected transfer duration.
5.2 Temperature Monitoring Setup
- Use calibrated data loggers placed at representative locations (e.g., center and periphery of payload).
- Activate temperature loggers and record device ID and calibration due date in Annexure-1.
5.3 Packaging and Loading
- Condition refrigerant packs at required temperatures (e.g., 2–8°C or –20°C) for minimum 24 hours prior to use.
- Assemble shipper per vendor’s packing instruction: refrigerant layer, product containers, buffer pads, and logger placement.
- Seal shipper with tamper-evident tape and label externally with:
- “Refrigerated Product – Do Not Freeze”
- Shipping location
- Contact person
5.4 Transfer and Handover
- Transport shipper using clean, qualified trolley or vehicle maintaining recommended temperature range.
- Ensure transfer is completed within maximum hold time defined in the BMR or validation study.
- Receiver must verify outer condition, temperature logger status, and document observations in Annexure-2.
5.5 Deviation Handling
- If temperature excursions are recorded or packaging is compromised:
- Quarantine affected shipment
- Initiate deviation form (Annexure-3)
- QA to assess product impact and disposition
6. Abbreviations
- BDS: Bulk Drug Substance
- GMP: Good Manufacturing Practice
- QA: Quality Assurance
- QC: Quality Control
7. Documents
- Temperature Logger Activation Log – Annexure-1
- Cold Chain Transfer Record – Annexure-2
- Temperature Excursion Report – Annexure-3
8. References
- WHO TRS 961 – Model Guidance on Storage and Transport of Time- and Temperature-Sensitive Products
- ICH Q1A – Stability Testing of New Drug Substances
- FDA Guidance on Transporting Biologic 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: Temperature Logger Activation Log
| Date | Logger ID | Batch No. | Storage Range | Cal. Due Date | Activated By |
|---|---|---|---|---|---|
| 04/05/2025 | TL-0221 | BS-BULK-052 | 2–8°C | 12/09/2025 | Ajay Verma |
Annexure-2: Cold Chain Transfer Record
| Date | Batch No. | From | To | Start Temp | End Temp | Received By |
|---|---|---|---|---|---|---|
| 04/05/2025 | BS-BULK-052 | Manufacturing | Fill-Finish | 5.0°C | 5.1°C | Sunita Reddy |
Annexure-3: Temperature Excursion Report
| Date | Batch No. | Excursion Detail | Duration | Disposition | QA Reviewer |
|---|---|---|---|---|---|
| 04/05/2025 | BS-BULK-052 | Exceeded 8.0°C | 18 minutes | Accepted – No impact | Dr. Neha Rao |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 04/05/2025 | 2.0 | Included logger documentation and passive shipper validation | Regulatory Audit Compliance |