The CVPF is a unit within the Division of Transfusion Medicine and Therapeutic Pathology in the Department of Pathology and Laboratory Medicine at the University of Pennsylvania. The CVPF is accredited by the Foundation for the Accreditation of Cellular Therapy (FACT). The CVPF is a university shared-core resource that supports cellular therapy clinical trials which include manufacture of activated and expanded T lymphocytes, dendritic cells, mesenchymal stem cells, and lentiviral vector and RNA gene-modified T lymphocytes, among others to support investigators at UPenn and collaborating institutions.

CVPF consists of three manufacturing facilities: Maloney, Ravdin, and the Center for Advanced Cellular Therapies (CACT). The three manufacturing spaces share the same Quality Control Laboratory unit, and the Quality Assurance unit, who leads the CVPF Quality Management System and releases all manufactured products at CVPF. The CVPF manufacturing facilities are designed to maximize isolation of the cell and vaccine processing from other building areas, utilities, and activities. Access to the CVPF cleanroom areas is restricted via card-access and/or key lock access leading to a dedicated gown-in entrance. The Air Handler Units (AHU) serving each facility provide 100% outdoor air filtered by high efficiency particulate air (HEPA) filters. They operate as constant supply air-volume systems to maintain constant airflow to the spaces in the manufacturing suites, and to maintain cleanroom classifications.

CVPF-Maloney
The Maloney Facility of CVPF is located on the sixth floor of the Maloney Building of the Hospital of the University of Pennsylvania (HUP). CVPF-Maloney opened in 2005 and consists of 1,880 square feet (ft2). As of July 1, 2016, the facility has six active processing rooms and a media preparation room, along with dedicated gown-in and gown-out entrances. Two of the six processing rooms are prioritized for HIV processing. The Maloney manufacturing suite is class 100,000 (ISO 8) and processing is performed in class 100 (ISO 5) Biological Safety Cabinets (BSCs).

CVPF-Ravdin
The Ravdin Facility of CVPF is located in approximately 2,000ft² of space on the third floor of the Ravdin Pavilion at HUP. CVPF-Ravdin is in direct proximity to the apheresis cell collection and infusion unit, the autologous and allogeneic blood donor center, the blood bank, and the stem cell processing facility that supports the clinical transplantation service. The facility consists of seven processing rooms, a gown-in/gown-out room, a media preparation and storage room. The interior hallway and common areas are class 100,000 (ISO 8) and the individual cell processing rooms are class 10,000 (ISO 7). Processing is performed in class 100 (ISO 5) BSCs.

CVPF-CACT
The CACT Facility of CVPF is the newest manufacturing facility, opened in July 2016 and located on the ninth floor in the newly built South Tower building, adjacent to the Smilow Translational Research Center on the University of Pennsylvania’s campus. The CVPF-CACT cleanroom manufacturing space consists of eight processing cleanrooms, an automation room, a media prep room, and gown-in/gown-out rooms. The interior hallway and common areas are class 100,000 (ISO 8) and the individual cell processing rooms are class 10,000 (ISO 7). The CVPF-CACT footprint of the clean room manufacturing area is approximately 4,500 ft². Processing is performed in class 100 (ISO 5) BSCs.

Quality Control Laboratory
The CVPF-CACT facility also contains the Quality Control (QC) laboratory space that also serves Maloney and Ravdin. The QC lab supports investigational product scale up, validation, and clinical manufacturing by qualifiying critical reagents including media to release for use in clinical manufacturing and performs analytical testing for in process and product release requirements that include sample characterization via FACS analysis, testing for mycoplasma and endotoxin, and sterility testing.

Critical Equipment Monitoring and Maintenance
Critical equipment in the CVPF is monitored continuously by the Rees Centron Environmental Monitoring System that is password protected and can be accessed remotely to provide information on the status of critical equipment, for example, incubators and freezers. The Rees sensors record parameters once every 15 minutes and will alarm if these parameters reach conditions outside of the pre-established acceptance criteria. All three facilities are cleaned at predetermined frequencies by trained staff, according to approved internal procedures. Critical cell processing equipment, such as Biological Safety Cabinets, is disinfected before and after each use, and ancillary equipment is cleaned after use, such as scales, and water baths. Common processing equipment is stored in a cleanroom central area and brought into culture rooms as needed. Single use disposable tubing sets are utilized to process the cells to reduce the risk of cross-contamination. Closed system processing steps are used whenever technically feasible. Finally, viable and non-viable Environmental Monitoring is performed at all three facilities.

Name of equipment
20/50 EHT Bioreactor	4' laminar flow hood
5' laminar flow hood	6' laminar flow hood
BACTEC© 9050 Blood Culturing System	BACTEC© FX Blood Culture System
Baxter MaxSep Magnetic Separator	Centrifuge, Microcentrifuge
Centrifuge, Sorvall Bifuge Primo R	Centrifuge, Sorvall Legend RT
Centrifuge, Sorvall Legend XTR	Centrifuge, Sorvall RC3B-plus
Coulter M3 Cell Counter/Sizer	Coulter M4 Cell Counter/Sizer
Counterflow Centrifugation Elutriator	Digital balance
Filtered potable water	Flow cytometer, BD LSRFortessa
Flow cytometer, FACS Calibur with Cellquest software	Freezer, (-)30 °C
Freezer, (-)40 °C	Freezer, (-)80 °C
Freezer, Controlled Rate	Haemonetics Cell Saver 5 Autologous Blood Recovery System
HEPA filtered CO2 incubator	LN2 Freezer
LN2 Manifold Changeover	Microscope
Miltenyi CliniMACS Magnetic Separator	Plate Washer
REES monitoring system, server based (number of points monitored is indicated in parentheses)**	Refrigerator
Sebra Heat Sealer	Spectrophotometer
Table top CO2 incubators	Terumo Sterile Connect Device
Total Air Particle Counter	Viable Air Particle Sampler
Waterbath	WAVE 2/10 Bioreactor