Bavarian Nordic Smallpox Vaccine Facility, Kvistgård, North Zealand, Denmark

The Danish biotech company Bavarian Nordic is to set up a new smallpox vaccine production facility in Kvistgård, North Zealand, Denmark. The new facility is being set up to supply increased demand for smallpox vaccine around the world, following an increased awareness of the possibility of bioterrorism. 30 different governments worldwide have placed orders with the company or made serious enquiries.

Bavarian Nordic has acquired a production facility from the Finnish company Orion Pharma. The 9,000m² facility is situated 30 miles north of Copenhagen on a 26,000m² site. Bavarian Nordic is to make this location its administrative centre as well as its main production facility. The facility is to be completely refitted with brand new plant, equipment and facilities and will then seek both FDA and EMEA validation as a production facility. The total investment will amount to DKK250 million (€33.6 million, $41 million).

The plant will be ready for its refit by mid 2004 and the work should be completed in less than eight months to allow test production (validation series) to be completed by the third quarter of 2005. The plant should then be in full production by the final quarter of 2005, with the ability to produce 120 million doses per year of the new smallpox vaccine. The initial workforce will be 50 employees. There may be filling and packaging facilities established at the plant at a later date and this would require and additional 60 to 80 employees.

CONTRACTOR AND REFITTING

Novo Nordisk Engineering (NNE) has been given the contract to construct the new production facilities inside the acquired building. The production plant will be used for the production of a smallpox vaccine and possibly vaccines against other infectious diseases should the need arise. NNE is to assist Bavarian Nordic with the preparation of regulatory approvals for an assessment of the production facility's impact on the environment, the Environmental Impact Assessment (EIA) report. Following approval of the EIA report construction can begin.

The facility will include 1,100m² of Class B and C cleanrooms, tank farm storage facilities, two bioreactors (500 litre and 1,200 litre volumes) and the associated downstream processing facilities, along with steam on-line for clean in place (CIP) activities, and sterile water and water for injection for cleaning and producing batches of media for culture respectively. The vaccine production will be fully current Good Manufacturing Practice (cGMP) compliant and adhere to the current biotechnology safety rules for containment of the production process to protect the environment.

NNE has also been contracted to carry out a cleaning validation in case of a contamination of production from previous activities at the plant. This is required as part of the cGMP compliance validation. NNE will also reconstruct an administration block and 400m² of laboratory buildings for QC/QA activities.

BAVARIAN NORDIC VACCINE

In the search for a vaccine against HIV Bavarian Nordic came across a new type of MVA vaccine against smallpox, which it has tested and produced for three years. The Modified Vaccinia Ankara (MVA-BN) is Bavarian Nordic's lead vaccine vector and is based on an attenuated poxvirus.

Recombinant MVA-BN vaccines have a number of important characteristics including a high expression of antigens in target cells. They are also potent inducers of Cytotoxic T Lymphocyte (CTL) and antibody responses and have a high efficacy in humans. The MVA-BN vaccines are safer than other Vaccinia viruses since they are highly attenuated and do not replicate in mammalian cells. The new MVA-BN vaccine is well tolerated in immune compromised patients, is serum-free, has a high titre production and may be stored by freeze drying at 4°C.

The new MVA-BN vaccine is to be marketed under the name IMAVUNE and is currently in Phase II clinical trials, along with another similar vaccine based upon the MVA-BN vector to combat HIV. The smallpox vaccine was granted an Investigational New Drug (IND) designation in May 2004 by the FDA and this means that the drug is available for sale to governments such as the US, Germany, UK and Greece, which are stockpiling smallpox vaccines at the current time but are not available for general release until late 2005. At the current time, Impfstoffwerk Dessau-Tornau (IDT) manufacture the virus for Bavarian Nordic in Germany.

NEW SAFER VACCINE

Clinical studies have compared traditional Vaccinia smallpox vaccines, such as Dryax manufactured by Wyeth-Ayerst, with the Bavarian Nordic MVA-BN third generation smallpox vaccine IMMAVUNE and have found there are far fewer side effects. The new vaccine is safe to be given to patients in known high-risk groups such as immune compromised, elderly, pregnant and young patients, along with those suffering from atopic dermatitis. The previous vaccines would elicit a very severe response in, or be dangerous to, these high-risk patients. The US government is considering using this 'safer' vaccine for the entire nation. Bavarian Nordic is counting on winning a US government order of 30 million doses, which is due to be announced during the first half of 2004.

In 2003 Bavarian Nordic's smallpox vaccine turnover was DKK360 million. The company plans to collaborate with commercial partners for late stage development of its clinical products and for international marketing. The company has worldwide partners including Chiron and Epimmune (US), Gerolymatos (Greece), IDT (Germany) and Vaccine Solutions of Australia.

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