Root Cause Analysis for Cell Therapy Primary Packaging Damaged in Transportation
Challenge
A leading biopharmaceutical company developing novel cancer immunotherapy products identified a critical problem during transport validation of their CAR-T cell therapy product. Drug product bags sustained damage to their ports and tubing during a transport study, creating unacceptable risk for commercial shipments. The company needed to determine the root cause of that damage and validate a solution before moving forward.
Objectives
Modality Solutions conducted a two-phase engagement: a root cause failure analysis to identify why the bags were damaged, followed by a redesigned transport study to confirm the recommended changes eliminated the problem. The scope included:
- Root cause failure analysis of drug product bag damage observed during the initial transport study
- Analysis of primary packaging materials, dewar packaging configuration, and secondary packaging to understand failure mechanisms
- Comparison of observed damage patterns against historical shock data and commercial shipping conditions
- Review of historical shipment data and packaging damage rates to establish baseline risk
- Development of specific recommendations for packaging orientation and shipping configuration
- Design and execution of a follow-on transport study incorporating the recommended changes
Results
The investigation identified inconsistent packaging orientation as the primary contributor to bag damage. Drug product bags were being packed in multiple directions within the same cassettes, exposing ports and tubing to direct impact against metal cassette surfaces. At cryogenic temperatures, the tubing’s increased brittleness compounded the vulnerability. Standardizing port orientation across all cassettes addressed the root cause directly.
The follow-on transport study confirmed the fix. No damage was observed to any drug product bags. The validated packaging configuration was incorporated into the client’s standard operating procedures and supported their regulatory submission. The company received approval for their cell therapy product and now distributes with documented validation behind every shipment.
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