MSD Biologics Advanced Biologics Centre, United Kingdom
Avecia Biotechnology announced a $100m investment in a new advanced centre for biologics manufacture in Billingham, UK, in February 2002. Construction of the Advanced Biologics Centre in the northeast of England commenced on 25 March 2002. It remained on schedule and the first phase was completed and in production in late September 2003. A new site in Canada had also been considered.
The plant was constructed in two phases and has 40,000l of manufacturing capacity for the production of protein biologics from microbial cell lines. The first phase included the commissioning of two 5,000l bioreactors with independent separation and purification suites to allow multi-product manufacture.
The second phase project was based around the addition of two 15,000l bioreactors and associated independent separation and purification streams. The additional capacity was on-line and in full production by 2006. The fully operational facility is now capable of running four large-scale manufacturing campaigns simultaneously.
In February 2010, Avecia Biotechnology was acquired by MSD Biologics. MSD subsequently merged with Diosynth Biotechnology to form the MSD BioManufacturing Network. Fujifilm Corporation will acquire the MSD BioManufacturing Network as part of a definitive agreement signed between Fujifilm and Merck on 28 February 2010.
Fujifilm will acquire all equity interests of Diosynth Biotechnology and MSD Biologics (UK), the two wholly owned subsidiaries of Merck that own the assets of the MSD BioManufacturing Network. MSD will, however, continue with limited development and production activities with both the companies.
Contractors and construction
The contractor responsible for engineering, procurement and project management was WS Atkins, based in Leeds, UK. The architectural design services were provided by Clean Design, based in Stockton, UK. The two 5,000l bioreactors were designed and constructed in Switzerland by BioEngineering and were delivered on-site ready for installation on 7 October 2002.
The 10km of stainless steel pipework required for the first phase was installed in early June 2003. An integrated qualification team was formed by Avecia and WS Atkins and located on-site in June 2003.
Technical specification and facilities
The new plant consists of a 62,000ft² process building, a 15,000ft² GMP warehouse, an additional 8,000ft² for support areas and an additional 30,000ft².
The Billingham site already has an existing plant with 100/1,000l capacity bioreactors to provide smaller scale quantities of products for use in early stage clinical trials.
The new plant facilities allow transfer of processes to large-scale manufacture and the older plant can assume a process development role.
The new facilities include eight process suites equipped with independent air handling systems and Streamline technology (Chinook Engineering) for air quality monitoring. The process suites are equipped with ultra-pure water (USP24), clean steam for CIP and SIP procedures, effluent collection and inactivation facilities and the capability to add methanol, oxygen, ammonia, nitrogen, acid or alkali to ferments as required by process methodology.
The equipment includes two independent streams with 50l to 500l and 5,000l capacity. There will be a 10,000l fold/refold system for peptide processing and all the required facilities for downstream processing such as centrifugation, ultra-filtration, homogenisation and chromatography. There are also five quality control laboratories, which were completed and equipped during the summer of 2003.
Progress of validation
The first phase entered production in September 2003. An Avecia progress report, dated 3 July 2003, showed that nearly all the equipment was in place. Factory Acceptance Tests (FAT) have been carried out successfully on downstream processing equipment such as centrifuges, bioprocess controllers and ultra-filtration facilities during summer 2003.
Other plant systems which underwent commissioning during the same timescale were water purification, pure steam generation, cold rooms, product freezer, chilled water and process and instrument air systems. A Site Acceptance Test (SAT) was successfully carried out and passed in March 2003.
Government grants and employment
The Avecia investment in the plant at Billingham was supported by a government grant of £6.5m from the Department of Trade and Industry. The plant has brought over 300 science-based jobs to the northeast of England. The plant construction and support services to the plant have also provided much-needed employment.
The facility has been established as a major contract manufacturer and developer for the UK biopharmaceutical market. In June 2008, Avecia agreed a collaboration with Italian company MolMed for the production of the investigational drug ARENEGYR (NGR-hTNFa), a vascular tumour necrosis factor-alpha agent which is a peptide/cytokine complex that actively targets tumour vasculature.
Avecia has agreed to optimise the drug manufacturing process and provide scale-up for the cGMP production for the Phase III clinical trials at Billingham.
Avecia was closely involved in the production of biodefence vaccines at Billingham and in March 2008 sold off its biodefence vaccines business to PharmAthene of the US for $40m.
This unit and the workforce is still based at the Billingham site. The work involves the development of an rPA anthrax vaccine and a plague vaccine for which a $220m US National Institute of Health grant has been granted.