Making tomorrow's medicines

Contract biomanufacturing is turning into big business for Cobra Biomanufacturing. The company recently announced the signing of an agreement with Hawaii Biotech, of the US, to manufacture and supply material for clinical trials of vaccines against Dengue fever and West Nile disease.

Commenting on the agreement, Dr David Thatcher, ceo of Cobra, said: "this is a significant programme for Cobra and we are thrilled to have been selected by Hawaii Biotech. The announcement is a valuable endorsement of our ability to manufacture protein vaccine products for US clinical trials and demonstrates our continued ability to penetrate the North American biopharmaceutical market."

Providing services Cobra is a supplier of innovative manufacturing solutions to the pharmaceutical industry; largely biotech companies. It has a core competency in manufacturing gene therapy products, with a worldwide reputation in that area, that has expanded significantly to therapeutic proteins and virus manufacture for early clinical trials. Founded in June 2002, the company was then the manufacturing division of a gene therapy company called Cobra Therapeutics. The name has nothing to do with snakes: it stands for Clinical Oncology Birmingham Research Associates, and was set up as a gene therapy for cancer platform, being a typical VC-backed r&d company, founded in 1992. However, at that time there were no opportunities for outsourcing the manufacture of these sorts of products, and by 1998, although everything was set to go in the manufacturing division, there were no products to manufacture, which led Thatcher to lead a team and go out and sell its services to the wider biotech community. "We have been very successful at that, doubling revenues year-on-year ever since that time. For the first eight years of its existence, the contract manufacturing side had very little visibility within the company, but by 2002 the 'cuckoo' had kicked the r&d egg out of the nest," he said. The core competency of Cobra is in providing manufacturing services for DNA, therapeutic proteins and virus products. Most of the technical staff are from a protein background. To meet the growing demand for such contract services the company doubled its capacity when the Oxford site came on stream. This followed a nine-month refurbishment of an old British Biotech site, which Thatcher said was a better alternative to a two-year wait for a new facility on a green field site. At a cost of around £7m, the facility is certainly impressive.

Challenges ahead The challenge of turning an old facility into a state-of-the-art sterile unit should not be underestimated, as Amanda Weiss, Cobra's associate director of fermentation, explained on a tour of the site. "There used to be three fermentation labs and the associated processing areas downstairs. What we did was to rip out the whole of upstairs, but to keep the clean areas, make them slightly bigger, and introduce our own inoculation rooms. "We now have a mirror image facility that will hold 130-litre microbial fermenters and a 140-litre mammalian fermenter with associated chromatography area; a communal wash-up; autoclave and prep area in the middle." The facility is validated for cGMP manufacture of proteins, both mammalian and microbial, plasmid DNA, virus and live cell products. In fact there are three independent cGMP suites, each with inoculum preparation, fermentation and downstream processing. The fermentation halls are Class 100,000, while the associated inoculum preparation rooms are Class 10,000 as are the DSP purification labs. As Weiss said: "the wash-up area and media-prep area are also Class 100,000. However, when an operator leaves the wash-up area to go into either of the fermentation streams, there has to be a change so that those areas remain segregated." The addition of the two microbial fermentation suites facilitates the production of plasmid DNA and microbial vaccines, as well as the expression of recombinant therapeutic proteins. Smaller units of 7.5 litres and 30 litres enable clients to develop their microbial fermentation processes on a cost-effective basis, and development progress includes those for gene therapies and vaccines. The third suite, which houses animal cell bioreactors of 30 and 140 litres, provides the capacity for the production of mammalian protein therapeutics, viruses for gene therapies and immuno-therapeutics. Such volumes enable scale-up from Phase I to Phase III production and the market supply of virus products. To further increase its quality capabilities and strengthen compliance with the latest EC clinical trials directive, Cobra appointed Nick Hill as director of quality at Oxford. He will act as Qualified Person (QP). "Nick's appointment follows the commissioning of our new cGMP biomanufacturing facility in Oxford," commented Thatcher.