08/02/07

Before and after: (Left) a typical room with Georgian windows in UCHL’s building and (Right) the refurbished interior with same window in background

Close collaboration between the central London hospital’s pharmacists and Clean Room Construction (CRC) project team has resulted in a modern facility which is regarded as a key element of the National Health Service’s strategy to develop better pharmaceutical manufacturing within hospital pharmacies. The hospital pharmacy was awarded a government grant to create the facility in a bid to overcome shortage problems associated with the commercial supply of drugs.

Diagnosis

Demand for pharmacy aseptic services is growing, partly due to the support required for the hospital’s important clinical work in the areas of intensive care, surgery, gastroenterology, cancer, paediatrics and neonatology. The demand is likely to increase further with the expected publication of National Patient Safety Agency guidelines on promoting the safe use of injectable medicines in the spring.

The brief from UCHL focussed on the need to bring all the pharmacy manufacturing and quality control facilities on to one site and to create a modern aseptic dispensing facility.

Prescription

Although the aseptic unit design might have included hydrogen peroxide gassing (a sanitisation process capable of Log 6 spore reduction), it was clear early on that the budget would not allow this approach. Space in the hospital was even more scarce with the old basement staff canteen identified for the new tablet manufacturing unit (120m_) and the 4th floor of the building (900 m_) earmarked for the aseptic and repack units.

Ian Isted, CRC’s projects manager, said: “The project presented many challenges for our team to overcome. It was an old hospital in central London and the site was occupied. As well as working with very restrictive heights and at two levels, a basement and a fourth floor, we were up against a tight deadline and budget constraints. Internal pillars, two stairwells and lift shafts also had to be accommodated in the design for the new facility.”

A former central corridor with rooms on each side has now been turned into grade C preparation cleanrooms which are served by Grade D support areas on one side and grade B dispensing cleanrooms on the other. A central lift shaft and stairwell split the middle part of the building into two separate areas. The result was a design for two separate aseptic facilities, each with a dedicated HVAC, effectively segregating the aseptic dispensing of chemotherapy drugs from other non-cytotoxic medicines. The support offices and plant room have been located between the two aseptic facilities.

A second stairwell has separated the aseptic facilities from non-sterile manufacturing, comprising grade D clean areas for repacking and over-labelling medicines, and dedicated rooms for the preparation of medicines for internal use, such as mixtures and suspensions, and external use, such as creams and ointments.

The tablet manufacturing facility has a grade D process area with dust control booths in the process room, providing dedicated areas for weighing, mixing and granulation and compression. The booths, manufactured by CPS Extract, re-circulate, through safe change filters and ceiling HEPA (H14) filters, 1,200 air changes per hour. These changes are designed to control air borne dust, within a safe working zone, to below 100µg/m_. Since alcohol is used in one of the granulation stages, detectors have been installed in the booths to alarm if alcohol vapour exceeds 25 per cent of the lower explosion limit.

Principal pharmacist Tony Murphy says: “We opted for class II biological safety cabinets rather than isolators as grade A work zones for the dispensing of cytotoxic, antibiotic, antifungal and antiviral injections. Visits to large commercial aseptic dispensing units which used unidirectional air-flow workstations and good work practices in well-controlled environments showed us that a classical design would achieve exceptionally good microbiological control. In addition to staff training and validation, the key is good workflow and segregation of processes.

Left: Blending and mixing equipment in the Grade D tableting suite. Right: A combined stainless steel pass through and trolley hatch into a Grade D area.

Segregation of processes

Three stages of garment change lead into the production areas:

1) Cleanroom labcoat for grade D support areas;
2) Sterile two-piece cleanroom garment with clogs for the grade C preparation areas;
3) Sterile grade B cleanroom coverall (donned over the grade C garment) and overboots for the grade B cleanrooms.

Store areas connect to grade D assembly rooms via trolley hatches. The assembly areas hold no more than two to three days stock. Following assembly checks, components are sprayed with 70 per cent alcohol and wiped before transferring through hatches into the grade C preparation area. In the grade C area components are sprayed with 70 per cent alcohol and wiped before transferring through hatches into the grade B cleanrooms. Dispensed medicines are transferred through hatches into the grade C area for inspection and then into a grade D final check room prior to release.

Vinyl cladding has been used for floors, walls and ceilings in the grade B and C cleanrooms and change areas. A Facility Monitoring System (FMS) has been installed to continuously measure room air particle counts in the grade B cleanrooms, with sample points in all other areas. The FMS also monitors room pressure differentials and refrigerator temperatures.

Remedy

Isted concludes: “The completed facility encompasses four zones of air conditioning, automatic room pressure and particle monitoring as well as robust services. Power cuts are frequent occurrences in old buildings and the services are designed to cope with this sort of disruption to maintain a clean environment.

“A challenging environment like this requires a genuine commitment to a partnership approach from the outset. The CRC team worked closely with the pharmacists to ensure that we created a customer-specific solution. The cooperation and support we received from principal pharmacist Tony Murphy and his team was crucial to the design and construction of a first class facility which meets all the customers’ needs.”

Murphy adds: “The professional approach adopted by Clean Room Construction for this complex design and build project has led to the production of an impressive facility here at University College Hospital London.”

Microbiological testing is now under way and it is hoped that aseptic preparation can begin in March. Aseptic preparation requires regular external audit by pharmacy QA specialists. However, the UCLH pharmacy team plan to manufacture medicines for which a licence is needed. This ‘specials licence’ is required when medicines are manufactured as ‘a batch’ for more than one patient, when the expiry period on the product exceeds seven days (sterile medicines)/28 days (non-sterile medicines), or when the medicine is prepared for another hospital. While the majority of injections are administered within 72 hours of preparation, there are instances when patients need home therapy requiring the manufacture of injections in advance of use.

Licensed manufacture is expected to begin in May 2007.