The development of this facility marks a substantial investment for Ortho Clinical Diagnostics (OCD). The company is part of Johnson & Johnson, the world's most comprehensive and broadly based manufacturer of healthcare products and related services for consumer, pharmaceutical and medical devices and diagnostics markets. The new 110,000 square foot facility will, when fully operational, employ more than 350 people in manufacturing operations, quality, regulatory, product support, human resources, finance and information technology.
Located on the Pencoed Technology Park, north-west of Cardiff, the facility will replace the company’s existing Cardiff plant by the end of 2010. The first product was shipped from Pencoed in April 2009, and existing Cardiff staff members are in the process of transferring to the new Pencoed facility. This phased approach is essential due to the extensive regulatory licence procedures necessary to make highly sophisticated diagnostic tests for multiple disease states available to markets worldwide.
Enhanced chemiluminescence chemistry
Today, immunodiagnostic tests from OCD are used as an aid to the diagnosis and management of disease in many clinical categories, including thyroid function, reproductive endocrinology, cardiology, anaemia, metabolism, oncology and infectious disease. The 48 different tests manufactured by OCD in South Wales utilise a proprietary technology, enhanced chemiluminescence (ECL), to provide the essential sensitivity for this type of testing.
First made commercially available for just five tests in 1985, this fast yet ultrasensitive measuring technique enables detection of hormones at extremely low concentrations. A British discovery made by scientists at the Wolfson Research Laboratory, Birmingham University, and developed by a forerunner of OCD (Amersham International), ECL testing opened the way to measuring hormones and other substances in the blood without using radioactive materials. It gave laboratories access to a system that matched the sensitivity of radioimmunoassay, enabling detection of quantities as small as one million millionth of a gram, without the associated risks.
Enhanced chemiluminescence uses purified horseradish peroxidase (HRP) enzyme linked to a wide range of antibodies/antigens. Tonnes of horseradish crop must be harvested to create just grams of the enzyme. The resulting conjugates are then purified before being diluted up to 50,000 times to use as test reagents. These catalyse the oxidation of luminol in combination with an enhancer, 3-chloro 4-hydroxyacetanilide, which generates a light signal. The addition of the enhancer enables the weak signal of conventional luminescence triggered by the presence of the target antigen in the sample to be intensified several hundred times, and the luminescence to be sustained for accurate measurement.
Combined with ECL, MicroWell technology plays a crucial role in delivering excellent assay performance for high-quality results. An assay-specific coating solution (eg streptavidin, antibody or antigen) is applied to each MicroWell using a highly automated system that can coat more than 30 MicroWells every second. A laser sensing system then checks the height of the meniscus in each well before the start of the timed incubation period. This can vary from a few minutes to several hours, and the process is managed by a robotic handling system. The MicroWells are then washed and dried prior to packing in a temperature- and humidity controlled environment.
The sensitivity of OCD’s ECL allows a wide range of immunodiagnostic assays, serum proteins, antibodies and hormones to be developed.
Local expertise, global market
Each year, OCD in South Wales manufactures more than 100 million tests which use ECL. The vast majority of these are shipped to OCD distribution centres in Strasbourg, France and Memphis, Tennessee, for hospital laboratories, public health laboratories and blood banks worldwide.
The manufacture of immunodiagnostic patient tests is necessarily a highly regulated biomedical process, which involves state-of-the-art technology and expert staff. Tight regulation means that OCD has a team of around 60 people at Pencoed continually engaged in quality control, process monitoring and the highly detailed work associated with regulatory submissions.
Even before its new investment in the Pencoed facility, OCD had almost 30 years of manufacturing history in Wales. Today, OCD employees in Wales – of whom around one-third are qualified to degree level and above – have more than 4000 years of collective experience in this highly specialised sector.
John Gethin, Pencoed operations general manager, says: “We undertake collaborative work with research laboratories, and managing that aspect of our business demands highly qualified personnel. Around 9% of our staff have PhDs and we also require high skill levels within the manufacturing process.”
Some of the processes used in the manufacture of immunodiagnostic tests, such as computer-controlled freeze-drying (lyophilisation), dispensing and packaging/labelling, can be found on manufacturing sites in many other sectors; however, other aspects of the manufacturing process at Pencoed are unique.
The production process begins with more than 800 raw materials, ranging from biologicals and chemicals to plastics and packaging, sourced from a global supply base. In terms of price per gram, the most costly of these is over a million times more expensive than gold.
Lean and green
Ortho Clinical Diagnostics began to apply Lean methodology at its original manufacturing facility at Forest Farm, Cardiff, some nine years ago. The results were dramatic: the site now produces twice the volume with similar levels of staff, while at the same time inventory costs have been controlled and customer supply is the best in class.
Having experienced the considerable benefit of applying these principles to its business operations, OCD then went on to establish its own Valumetrix service to share this knowledge with clients seeking to overhaul their clinical laboratory practices.
John Gethin says: “The standardisation involved in the application of Lean is perfect for a regulated environment like ours. It means that we consistently score well in external audits by bodies such as the FDA and ISO, as well as in our frequent internal audits. It has also been of tremendous value as we designed the new facility, enabling us to create what is effectively a huge U-shaped cell for maximum efficiency of product flow.
“The Lean approach is also responsible for some key aspects of production and goods management on the site, such as ‘Kanban’ stock control, which saves costs by keeping inventory to a minimum. Further along the production process, Lean methodology has led us to create in-house ’supermarkets’ of semi-finished goods that can be finished quickly to meet customer demand.” He adds: “From the outset, there has been a place for everything, and everything in its place at both sites; something which kept any disruption associated with the relocation to a minimum.”
Naturally, the design of the new Pencoed facility also reflects OCD’s commitment to environmental responsibility. Waste water from the manufacturing process is recycled to flush toilets, while variable speed drives on the motors that operate air compressors and fans enable them to respond intelligently to changing conditions. High-efficiency lighting incorporates a ‘daylight dimming’ feature that adapts to natural light levels, and there is a high level of insulation throughout the building. Fifteen trees and eight hundred shrubs have also been planted in the grounds.
Advanced systems
The opening of the new facility enables OCD to continue to provide its customers worldwide with advances in diagnostics that improve patient care. Importantly, immunoassays made in South Wales are used by both the VITROS 3600 Immunodiagnostic System and the VITROS 5600 Integrated System launched by OCD last year, as well as by the VITROS ECi/ ECiQ Systems launched in 1997.
The new VITROS 3600 Immunodiagnostic System is a high-volume immunoassay system. Designed for continuous operation and with a large onboard menu capability, it features an advanced microimmunoassay centre. Reagents can be changed while the system is in use, permitting uninterrupted processing of assay results. All stages of the immunodiagnostic process are verified and documented by Intellicheck technology.
The VITROS 5600 Integrated System is an integrated clinical chemistry and immunoassay system, using an elegant combination of proven MicroSlide, MicroTip and MicroWell technologies to deliver the unmatched ease-of-use, reliability and efficiency for which VITROS systems are renowned. It has a sample-centered approach to integration with a single point of access for loading, retrieval and unloading, providing consistent and fast turnaround times, independent of sample and assay mix. As assays are performed without plumbing, drains or fixed probes, there are significant productivity advantages over traditional chemistry systems.
Ortho Clinical Diagnostics’ systems are also used in many parts of the world to screen blood for the presence of infectious disease to ensure the safety of the blood supply.
John Gethin concludes: “We were honoured that HRH The Prince of Wales was available to share in our enthusiasm for bringing innovation and new technologies to Wales, the rest of the UK and our customers worldwide.”