Introduction
This guide covers the fundamental protocols required for GMP-compliant cell therapy manufacturing, from facility setup to release testing.
Note: All protocols should be validated for your specific cell type and indication.
Facility Requirements
Cleanroom Classifications
Cell therapy manufacturing typically requires:
- Grade A/B for open processing
- Grade C/D for closed system operations
- Appropriate airflow and pressure differentials
Environmental Monitoring
Continuous monitoring is essential for maintaining GMP compliance:
- Particle counts (viable and non-viable)
- Temperature and humidity logging
- Pressure differential alarms
- Personnel gowning verification
Cell Processing Protocols
Isolation and Expansion
The core steps for most autologous therapies include:
- Patient material receipt and inspection
- Cell isolation (density gradient, immunomagnetic selection)
- Culture initiation and expansion
- Harvest and formulation
- Cryopreservation or fresh release
Critical: Maintain chain of identity throughout processing. Label verification at each step is mandatory.
Media and Reagent Management
All media and reagents must be:
- GMP-grade or equivalent qualification
- Received with certificates of analysis
- Stored per manufacturer specifications
- Used within validated shelf life
Quality Control Testing
In-Process Controls
| Control Point | Test | Frequency |
|---|---|---|
| Day 0 | Cell count, viability | Each batch |
| Mid-culture | Sterility sample | Each batch |
| Pre-harvest | Phenotype check | Each batch |
Release Testing Panel
| Test | Method | Acceptance Criteria |
|---|---|---|
| Sterility | USP <71> | No growth at 14 days |
| Endotoxin | LAL | <5 EU/mL |
| Mycoplasma | PCR | Negative |
| Identity | Flow cytometry | >70% target phenotype |
| Viability | Trypan blue | >70% viable |
| Potency | Functional assay | Product-specific |
Documentation Requirements
Batch Records
Every manufacturing run requires:
- Pre-approved batch production record
- Real-time documentation of all steps
- Deviation reporting and investigation
- Final review and release
Best Practice: Document everything in real-time. Retrospective documentation increases error risk and regulatory scrutiny.
Change Control
Any modification to validated processes requires:
- Change request submission
- Impact assessment
- Approval by Quality Assurance
- Implementation and verification
- Documentation update
Summary
Implementing robust protocols is the foundation of successful cell therapy manufacturing. Key takeaways:
- Facility design must support your product requirements
- Process controls ensure consistency batch-to-batch
- Quality testing confirms product safety and efficacy
- Documentation provides the evidence trail regulators require
For assistance implementing these protocols in your facility, contact our consulting team.