All aspects of Production are performed in MHRA-accredited cleanrooms to GMP standards. Dedicated, highly-trained staff are responsible for maintaining the cleanliness of the rooms, as well as ensuring all equipment is routinely serviced and calibrated. The cleanrooms comprise 9 separate work areas, conforming to EU GMP Grades C and D, in which Microbiological Safety Cabinets and a pharmaceutical isolator conforming to EU GMP Grade A standards for microbial and particulate cleanliness are sited. The cleanrooms are certified annually to ensure that the number of air changes and particles remain within specification for their grade. Routine environmental monitoring is also undertaken to ensure that the rooms adhere to appropriate GMP standards; environmental monitoring during all manipulations takes place to demonstrate that work areas achieve the required grade of cleanliness. Rooms are released for use by Quality Assurance before any critical work takes place.
The CBF has a dedicated cleanroom for the production of master and working cell banks. Once the banks have been checked for sterility, they are stored in a liquid nitrogen freezer in vapour phase before being sent to a Contract Testing Organisation for full testing. A number of vials from all critical cell banks are archived off site at an approved storage facility.
The CBF has the capacity to propagate cells and virus with the aid of several key pieces of equipment, including multiple Microbiological Safety Cabinets, shaking incubators, and floor standing low-speed centrifuges. This allows for simultaneous expansion and harvest throughout the process, thereby minimising down time. Cellular DNA removal treatments may be performed, after which the lysed cell suspension containing the virus is clarified and frozen, until ready for downstream processing.
Once the cells and virus have been harvested and clarified, the intact virus particles must be purified from the contaminating cellular debris and empty viral capsids through a series of ultracentrifugation or chromatography steps and ultimately, a desalting and formulation process to ensure the virus is in a stable formulation buffer until it is ready to be aseptically filled.
The CBF has a dedicated EU GMP Grade C filling room where manual fills are carried out in a EU GMP Grade A pharmaceutical isolator. Filling operators are qualified by performing media simulation fills in triplicate and are re-qualified every six months. Adjacent to the filling room is a EU GMP Grade D Inspection and Labelling room, where filled and crimped vials are passed to the Quality Assurance team who perform the initial inspection and labelling.