All aspects of Production are performed in MHRA-accredited clean rooms to GMP standards. Dedicated, highly-trained staff are responsible for maintaining the cleanliness of the room, as well as ensuring all equipment is routinely serviced and calibrated. The clean rooms comprise 9 separate work areas and 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 also 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 clean room for the production of master and working cell banks. Once the banks have been checked for sterility and mycoplasma status, they are stored in a liquid nitrogen freezer in vapour phase. A number of vials from all critical cell banks are archived off site at approved storage facilities.
The CBF has the capacity to propagate cells and virus to large scale with the aid of several key pieces of equipment, such as multiple Microbiological Safety Cabinets, shaker incubators, roller incubators and floor standing low-speed centrifuges. The combination of these pieces of equipment allows for simultaneous expansion and harvest throughout the process, thereby minimising down time. Various cellular DNA removal treatments may be performed, after which the cell suspension 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 capsids through a series of ultracentrifugation or chromatography steps and ultimately, a desalting process to remove residual caesium chloride and to ensure the virus is in a stable formulation buffer until it is ready to be aspetically filled.
The CBF has a dedicated filling room where manual fills are carried out in a Grade A pharmaceutical isolator. Continuous particulate monitoring in the Grade A area is performed. Filling operators are qualified by performing media simulation fills in triplicate and must be re-qualified every year. Adjacent to the filling room is a product inspection room, where filled and crimped vials are passed to the Quality Assurance team who perform the initial inspection and labelling.