Standard Operating Procedure for Handling Cold Chain Breaches During Sample Storage in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/112/2025 |
| Supersedes | SOP/BA-BE/112/2022 |
| Page No. | Page 1 of 10 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To define the procedure for identifying, documenting, investigating, and mitigating cold chain breaches during the storage of clinical samples in Bioavailability/Bioequivalence (BA/BE) studies.
2. Scope
This SOP applies to all clinical and laboratory personnel involved in handling, storing, and monitoring biological samples (e.g., plasma, serum) under cold chain conditions (-20°C, -70°C) in BA/BE studies.
3. Responsibilities
- Sample Storage Technician: Monitors and logs storage temperatures; notifies deviations immediately.
- QA Officer: Investigates breach events and reviews CAPA implementation.
- PI/Study Manager: Evaluates sample usability and decides on repeat sampling or exclusions.
- IT/Engineering: Maintains monitoring systems and calibrates temperature devices.
4. Accountability
The Head of Laboratory Operations is accountable for ensuring uninterrupted cold chain management and responding promptly to any breach to prevent data loss or regulatory non-compliance.
5. Procedure
5.1 Cold Chain Infrastructure and Monitoring
- Ensure all sample freezers are:
- Maintained at specified temperatures: -20°C or -70°C
- Fitted with calibrated digital temperature monitors
- Connected to 24/7 temperature alarm systems
- Log temperatures at least twice daily in Annexure-1: Cold Chain Temperature Log.
5.2 Identification of Breach
- Breach is defined as any temperature excursion beyond:
- -20°C ± 5°C for medium-term storage
- -70°C ± 10°C for long-term storage
- Upon breach detection (via logger or manual check), immediately inform QA and PI.
5.3 Initial Response
- Label affected freezer “DO NOT USE”.
- Relocate samples to backup storage unit within 15 minutes, if conditions are unsafe.
- Document relocation and status in Annexure-2: Cold Chain Breach Report.
5.4 Investigation and Documentation
- QA initiates a deviation investigation within 24 hours.
- Root cause analysis to be conducted using Annexure-3: Temperature Excursion Investigation Form.
- Assess sample integrity based on:
- Type of analyte
- Duration and temperature of exposure
- Stability data (refer to protocol or analytical validation report)
5.5 Corrective and Preventive Action (CAPA)
- Develop CAPA in coordination with QA and Facility teams.
- Implement engineering controls, retraining, or backup validation based on root cause.
- Document CAPA in Annexure-4: Breach CAPA Register.
5.6 Sample Disposition and Reporting
- PI to determine usability:
- If usable, retain with deviation note
- If not usable, report as lost sample and update sample reconciliation log
- Report to Sponsor, IEC, and Regulatory Authority if breach impacts study outcomes.
5.7 Preventive Monitoring and Maintenance
- Calibrate all sensors and loggers quarterly.
- Test alarm systems monthly and maintain documentation in Annexure-5: Alarm Function Test Log.
- Maintain service records for cold chain equipment.
6. Abbreviations
- BA: Bioavailability
- BE: Bioequivalence
- QA: Quality Assurance
- PI: Principal Investigator
- CAPA: Corrective and Preventive Action
- IEC: Institutional Ethics Committee
7. Documents
- Cold Chain Temperature Log – Annexure-1
- Cold Chain Breach Report – Annexure-2
- Temperature Excursion Investigation Form – Annexure-3
- Breach CAPA Register – Annexure-4
- Alarm Function Test Log – Annexure-5
8. References
- ICH E6(R2) – Good Clinical Practice
- ICH Q1A(R2) – Stability Testing Guidelines
- Schedule Y – Drugs and Cosmetics Rules
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Cold Chain Temperature Log
| Date | Time | Freezer ID | Temperature (°C) | Logged By |
|---|---|---|---|---|
| 17/04/2025 | 10:00 AM | FZ-20A | -21.3 | Rajesh Kumar |
Annexure-2: Cold Chain Breach Report
| Date/Time | Freezer ID | Max Temp | Duration | Samples Affected | Reported By |
|---|---|---|---|---|---|
| 16/04/2025 2:45 AM | FZ-20A | -12.5°C | 90 mins | 12 | Sunita Reddy |
Annexure-3: Temperature Excursion Investigation Form
| Cause Identified | Root Cause | Investigated By | Corrective Action |
|---|---|---|---|
| Door ajar | Manual error during transfer | QA Officer | Training scheduled |
Annexure-4: Breach CAPA Register
| Date | Issue | CAPA Description | Closure Date | Approved By |
|---|---|---|---|---|
| 17/04/2025 | Temp Breach | Retraining and equipment alarm testing | 18/04/2025 | QA Head |
Annexure-5: Alarm Function Test Log
| Date | Freezer ID | Alarm Triggered | Response Time | Tested By |
|---|---|---|---|---|
| 01/04/2025 | FZ-20A | Yes | 2 mins | Ajay Verma |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 12/01/2022 | 1.0 | Initial SOP Release | Cold Chain Compliance | QA Head |
| 17/04/2025 | 2.0 | Annexures added, updated deviation handling | Regulatory Audit Observation | QA Head |