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

1. Verify bulk product has passed all applicable in-process QC tests and QA release.
2. Confirm labeling on containers includes product ID, batch number, storage condition (e.g., 2–8°C), and status (Released).
3. 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

1. Use calibrated data loggers placed at representative locations (e.g., center and periphery of payload).
2. Activate temperature loggers and record device ID and calibration due date in Annexure-1.

5.3 Packaging and Loading

1. Condition refrigerant packs at required temperatures (e.g., 2–8°C or –20°C) for minimum 24 hours prior to use.
2. Assemble shipper per vendor’s packing instruction: refrigerant layer, product containers, buffer pads, and logger placement.
3. Seal shipper with tamper-evident tape and label externally with:
   • “Refrigerated Product – Do Not Freeze”
   • Shipping location
   • Contact person

5.4 Transfer and Handover

1. Transport shipper using clean, qualified trolley or vehicle maintaining recommended temperature range.
2. Ensure transfer is completed within maximum hold time defined in the BMR or validation study.
3. Receiver must verify outer condition, temperature logger status, and document observations in Annexure-2.

5.5 Deviation Handling

1. 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

1. Temperature Logger Activation Log – Annexure-1
2. Cold Chain Transfer Record – Annexure-2
3. 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