Elan Pharma is a biopharmaceutical company working in the development of drugs for the treatment of a wide range of therapeutic areas. The company has an established manufacturing and research facility at Athlone in the Republic of Ireland, which underwent a significant revamp in recent years (completed in June 2003). This cost in excess of €200m.
The investment of €200m in Athlone was an indication of a change in direction of the company to focus more on biopharmaceuticals. In June 2004 the construction of a new secondary pharmaceutical facility was started at the site in order to provide more capacity for the sterile finishing and filling of new drugs (biopharmaceuticals).
The company employs 550 personnel at the Athlone site and seems to have recovered from the financial problems it has seen since 2003–04. The new €35m biopharmaceutical plant started in June 2004 and completed in the third quarter of 2005 created 120 new jobs. The Ireland Development Authority (IDA) gave their support to the project along with the local county council (Roscommon County Council).
STERILE FILL AND FINISH FACILITY
The new secondary pharmaceutical facility (sterile fill and finish) is a 14,000m³ three-storey building which will be used for the production of oral solid dosage forms and also for the filling of vials. The project and construction manager for the project was Project Management Ltd (PM). The new facility was also accompanied by site infrastructure improvements including:
- New energy centre
- New thermal oxidiser
- Refit of the NCD suite
- Pivotal suite upgrade
- Solvent tank farm upgrade and expansion
The secondary pharmaceutical facility is a steel-framed, cladded, three-floor building, with an adjoining single-storey warehouse. The lower floor comprises utility areas, offices, garbing rooms and a final product inspection area.
All processing takes place on the second level. This includes component preparation and vial processing, which consists of washing, sterilising, filling, stoppering, capping and printing the batch number on the vial cap.
The warehouse block includes cold rooms for product storage and a raw material dispensing area. The facility was structurally complete by May 2005 and then underwent necessary validation and qualification processes, becoming ready for use in September 2005.
The new facility was constructed by the Irish construction company SIAC Construction. The company were responsible for all aspects of the construction including steel fabrication and erection and the pipe rack steelwork. In addition SIAC installed Kingspan composite cladding panels externally, a Levolux louvre system, Kawneer double glazed curtain walling and all roller shutter and steel external doors.
STATE-OF-THE-ART VISIBLE CLEANROOMS
The fill and finish processes occur almost exclusively within class 100,000 cleanrooms. It is well recognised within the industry that one of the greatest potential hazards to product contamination in a sterile filling operation arises from humans within the cleanroom. The Elan design (by PM) required the cleanrooms to be highly visible internally from the outside so that the need for personnel to enter the cleanroom is minimised.
Daldrop & Huber, the cleanroom builder, provided glass walls and doors. IMA, the filling line vendor, supplied a filling machine that was able to be mounted against a wall.
The design includes several full-height glass walls on a circulation corridor around the processing floor and two ‘inspection’ corridors with full-length glass walls. The inspection corridors penetrate deep into the cleanroom area but are not part of the cleanroom and are, therefore, accessible without having to enter it.
Visitors in the inspection corridor can see all operations at close quarters without having to enter the cleanrooms. The distance from an observer’s eye to the filling needles is less than 500mm. To a regulatory inspector, this provides an unparalleled level of visibility. Frequently, in such facilities, inspectors have to inspect operations from a distant window or by remote camera.
An alternative is to go through the facility’s in-house training and validation programme to permit entry to the cleanroom, a process which can take a week or longer to complete. The same benefit applies to supervisory staff, as they can observe and communicate with cleanroom staff without having to enter.
The machines positioned against the wall allow maintenance to be carried out from the outside.
A 100% check weigh feature on the filling line ensures that each vial is weighed before and after filling to provide absolute assurance that every vial has the correct quantity of product. This reduces the need for interrupting the fill operation and any associated risk of accidental contamination.
COMMUNICATION WITHIN THE CLEANROOM
An important principal in aseptic manufacturing is to reduce operator movement and especially hand contact of any kind. To this end, Project Management designed a wireless communication system into the cleanroom fabric. The system, more traditionally used in TV studios and theatres, allows operators and supervisors in different rooms to communicate without ever having to touch a keypad or switch.
NEW DRUGS AT ELAN
One of the new drugs to be filled and finished at the new facility will be the capsule form of Duloxetine Hydrochloride (Cymbalta, Xeristar). Duloxetine is a one of a new class of antidepressant drugs, called dual uptake inhibitors, being used to treat panic and anxiety disorders, major depression and Diabetic Peripheral Neuropathic Pain (DPNP).
The new drug is in a class of Serotonin and Noradrenaline Reuptake Inhibitors (SNRI). The Duloxetine manufacturing contract was awarded to Elan by Eli Lilly in June 2004 (contract started in mid-2005).