Charles River Laboratories’ Gene Therapy Division CQV Facility Expansion Validation Services Case Study

Charles River Laboratories’ Gene Therapy Division specializes in the development, manufacturing, and quality testing of advanced genetic medicines under stringent regulatory standards. Services include GMP-compliant plasmid DNA and viral vector production (AAV, lentivirus, retrovirus), process development, release and characterization testing, and biosafety assessment. With integrated capabilities spanning preclinical studies through clinical and commercial manufacturing, the division supports regulatory submissions by ensuring product quality, safety, and consistency. This comprehensive approach enables sponsors to navigate complex regulatory requirements and advance gene therapy programs efficiently from early-stage development to market approval.

• In November 2022, Charles River expanded its Memphis facility by adding nine new processing suites to its existing 16 clean rooms.
• This expansion followed approval from the European Medicines Agency (EMA) to produce allogeneic cell therapy drug products commercially, marking a first for a CDMO (Contract Development and Manufacturing Organization) in North America.
• The Memphis site became a major hub for clinical and commercial manufacturing of gene-modified cell therapies, including treatments for conditions like sickle cell disease.

The Validation team was hired by Charles River Laboratories’ Gene Therapy Division to Commission and qualify the nine-manufacturing room expansion and the associated support rooms, utilities, and systems. The Turnover packages from the construction company were compiled. Commissioning included the BMS (Building Management System), lighting, door interlocks, room and floor finishes, gas utilities, and electrical distribution. The commissioning timeline overlapped the construction timeline due to COVID delays in materiel and equipment delivery.

The challenge became balancing progress on commissioning and testing with the need to repeat testing as systems were completed. The partial commissioning required rooms and common areas to be retested when the construction modified them. This required flexible contracting hours, shift scheduling, and room-by-room release.

Key Project Details

• Client: Charles River Laboratories’
• Project Type: CQV Facility Expansion (9 production rooms
• Location: Memphis, Tennessee
• Project Costs: 50 million USD
• Project Duration: 12 Months
• Staff Assigned:
  • Senior Validation Manager
  • Senior CSV Engineer
  • 8 x Validation Engineers
  • 2 x Validation Technicians

The project faced several challenges, driven mainly by COVID-19 construction and material delays during the build phase. Instead of delivering one fully completed manufacturing area, we had to release systems, rooms, and areas in stages. This phased approach required repeating commissioning activities and updating turnover packages and certifications as rooms were modified or rebuilt to support ongoing work. As a result, commissioning and inspections proceeded room by room, with each area approved through a stepwise release.

Commissioning and qualification of the manufacturing expansion required close collaboration with the client’s Engineering team, Microbiology group, Quality Assurance (QA), and construction vendors. Through consistent communication, integrated scheduling, and coordinated testing over twelve months, the team completed the expansion and successfully executed the Environmental Monitoring Performance Qualification (EMPQ).

To support the EMPQ, room equipment was installed and qualified, and both particle counters and microbial air samplers were validated. These activities increased staffing demands and put pressure on the document approval workflow. We managed the impact through detailed scheduling, priority-based sequencing, and flexible work hours.

Key Project Take Aways

• Timely communication
• Detailed TOP’s

In working with the client, the Transcat Validation team executed the expansion commission, equipment qualifications, and Building Monitoring System (BMS). Services performed included:

• New BMS software with historian qualification (IQ/OQ/PQ)
• Coldbox (2°C-8°C) storage
• Warehouse storage (Room Temperature) with MKT calculations
• IQ/OQ of Cyro storage area and equipment
• New facility expansion, including nine manufacturing rooms and support areas
• Clean gas utilities such as nitrogen, oxygen, carbon dioxide, and clean compressed air
• IQ/OQ of Bio-Safety Cabinets, Incubators, Particle Monitoring systems, Air samplers, centrifuges, temperature baths, NC-200’s, PCR’s, cell counters, etc.
• Area SOP and Procedural verifications

The facility Commissioning qualification was completed successfully, and the validation packages were presented to regulatory agencies without observation.

Efficiency Benefits

• Single regulatory submission for new area (no observations)
• Allowed for the successful completion of the EMPQ
• Verified workflow streams before commercial production
• Daily EM and Training report for Production
• Allowed accurate scheduling for new production areas

Quality Improvements

• New modern production areas meeting all regulatory requirements
• Expanded single batch production due to increased incubator capacity