Development Programme:
July to December 2003
The foundations for the GMP facility were laid in early July and the building lifted into position on 30th of the month. This was a mammoth task, as each module had to be craned into position over a two storey building surrounded by trees and laid on its supporting piles. Though each unit weighed over 9 tons, the precision of the lift was such that the building was within 2 mm of its allotted position at the end of that day. Once in place the units were bolted together and work started on fitting out the shell. Much of the initial work on the electrical and air ducting systems had been undertaken prior to installation at NIBSC and work was able to proceed rapidly on fitting the internal sealed shell the completing these systems.
During August and September much of the heavy plant required to run the air handling system or HVAC - the air supply and extract fans and associated air filtration plant (commonly known as Air Handling Units or AHUs) – were installed in the plant room and linked to the ductwork (LINK TO PICTURE). In all 4 AHUs are employed within the cleanrooms to provide ultra-clean, HEPA-filtered, pressurised air. This air is fed to each laboratory and its associated airlock/change by an individual AHU through separate ductwork. This prevents air from one laboratory from mingling with that from another. There are three laboratories for cell processing within the facility, permitting up to three cell lines to be banked at any one time. The provision of a separate, re-circulating air supply to each laboratory thus ensures that there is no likelihood of airborne cross-contamination between laboratories.
The fourth AHU supplies air to the clean corridor and the outer airlocks which provide controlled access between the cleanrooms and the outside environment. Together, these four AHUs provide a pressure cascade through the facility. This ensures that air leaks outwards at all times: from the high pressure environment of the laboratories through the intermediate pressure of the clean corridor to the lower pressure airlocks/change. Thus the cell lines are continually protected from bacteria and other potential contaminants present in the outside environment.
In late September, the electric system was connected to the main NIBSC system through an Uninterruptible Power Supply (UPS). This provides emergency power to critical circuits such as the air supply, facility monitoring and alarm systems and incubators in the event of a failure of the mains supply. Also installed during this time was the vacuum insulated pipe-work and operating valves for the liquid nitrogen storage refrigerators. Stem Cell lines like many other cells and tissues can be stored at very low temperatures without loss of function. This is done in specially designed storage vessels that use liquid nitrogen, an ultra-cold liquefied gas, to keep the cells at temperatures below -180°C. Cells can be stored indefinitely in the chilled gas above the liquid phase and still retain their function if properly thawed.
Between October and December, the control, monitoring and alarm systems for the HVAC were installed and commissioned. The AHUs were switched on and the cleanrooms pressurised in late November. Once the ultra-pure, pressurised air supply was operational much of the equipment for cell banking could be installed and commissioned. This included Class II microbiological safety cabinets which provide the Grade A air environment necessary for the production of GMP-compliant cell banks. Also installed during this period were the liquid nitrogen storage refrigerators used to store the cell lines and the liquid nitrogen supply tanks holding the liquid nitrogen itself. The system provides automatic supply to and alarm monitoring of refrigerators to prevent any accidental thawing and loss of precious cell lines during storage.
A key issue in providing a GMP-compliant facility is demonstrating that the facilities and equipment are demonstrably fit for the purpose for which they are designed. This is a key element in quality assurance for Good Manufacturing Practice (GMP). In order to assess and record all components within the facility and the construction of the facility itself, the Bank has employed independent, specialist consultants (Jacobs Engineering) to work with the Bank and its main contractor (Clean Modules Ltd) and oversee the process of validation. The process involves the generation of qualification documentation (IQ, OQ and PQ – standing for Installation, Operation and Performance Qualification respectively) for each system and item of equipment that impacts on the banking of “Clinical Grade”, and therefore GMP-compliant cell lines (LINK TO PHOTO). The generation of the documentation involved hundreds of hours of work by Jacobs Engineering, NIBSC and the UKSCB to provide a series of documents that would demonstrate that the facility and equipment provided by the suppliers met the bank’s specification, operated in the way the suppliers intended and performed satisfactorily when used in the manner required by the Bank. This work, together with the process of building the Banks documented Quality system began in March 2003 and continued throughout the year.