The 1,500 sq. ft. facility is located on the main campus of Nationwide Children’s Hospital within the Center for Gene Therapy on the 3rd floor of Research Building II. Clinical products suitable for Phase I and Phase II clinical studies will be produced in this aseptic processing facility compliant with FDA regulations (CFR 21 Part 11, 210, and 211), that will ensure the safety, identity, purity and strength of the manufactured biologic. All vectors will be manufactured using cGMP and follow a linear flow of unit operations from scale-up of producer cells in single use Corning Cell Cubes or Stacks to manual final fill operations.
The CMF design incorporates uni-directional process, material, personnel and waste flows that are aided by electronic door interlocks to promote uni-directional flow. Controlled access is achieved using an electronic card key system. Environmental control within the facility is achieved using dedicated HVAC units that provide an ISO class 7 clean-room environment through a cascading system of room pressure differentials that allow air to flow from the cleanest room (Purification and Cell Bank Isolation Suites) to other rooms in the facility and is monitored and controlled in real-time using a Johnson Controls system.
CMF processes are directed by over 100 Standard operating procedures (SOPs) and Master Batch Record (MBRs) documents. This regulatory compliant document structure ensures that management-approved procedures are followed to ensure the integrity, reproducibility, and quality of data. SOPs and MBRs serve multipurpose functions: (i) they reduce the introduction of errors and variables by ensuring the consistent use of appropriate procedures; (i) communicate to the necessary people (e.g., client, project personnel) how work is to be conducted; (iii) increase the effectiveness of training by clearly and consistently communicating the approved method of performing a procedure, (iv) provide a historical record of technical procedures, and (v) provide a basis for data comparability. SOPs govern the use, maintenance, and calibration of equipment, analytical procedures, chain-of-custody procedures, data management and documentation procedures, and records management.
The CMF is supported by the Quality Control Laboratory (QC) which schedules and performs analyses as directed by Master Process Plans (In-Process Testing and Release Testing) and Stability Protocols. QC Lab equipment capabilities include qPCR Instrumentation, UV/VIS Plate Reader, Micro-volume UV/VIS Spectrophotometer, CO2 and Standard Incubators, Biosafety Cabinets, and Gel Documentation System w/ image densitometry. This allows the QC Lab to perform a wide range of assays including but not limited to Sterility, Environmental Monitoring, qPCR for product titration and contaminating DNA, In-Vivo based assays, ELISA, Colorimetric Protein Assays, and Electrophoresis Purity assays. QC also writes material specifications and inspects and quarantines materials used in manufacturing. QC directs the environmental monitoring (EM) program to ensure that the CMF operates within prescribed limits of viable and non-viable particulates within the facility.
The CMF is also supported by Quality Assurance unit (QAU) which assures that the standards for clinical manufacturing quality including facilities, equipment, personnel training, and work performance is being attained, and if not, to identify and report the areas that need improvement to meet those standards. This goal is accomplished through audits, inspections, and reviews. Quality Assurance reports quality issues to the Director, Clinical Manufacturing so that corrective action can be implemented at the appropriate level. Organizationally, the QA reports to the Director of Research Compliance and Integrity and is totally independent of manufacturing technical groups and staff. In addition, the QA is authorized to elevate manufacturing quality concerns to appropriate management levels. The QAU also serves as the controlled document administrator to maintain proper control over the document version and revision process.