The company is developing its vaccine Imvamune as an alternative for people contra-indicated to traditional smallpox vaccines, so the regulatory authorisation applies to the manufacturing, analysis and release of such smallpox vaccines for use in clinical trials and emergency situations.
Although the World Health Organisation declared the disease eradicated in 1979, new concerns have emerged in the US about the use of smallpox as an agent for bioterrorism following the terrorist attacks in New York and Washington DC exactly five years ago.
Smallpox has killed more people over the course of history than any other infectious disease and cannot be treated but only be prevented by vaccinations, therefore the US government is eager to stock up and has indicated to Bavarian Nordic it may acquire up to 20m doses of its MVA-based smallpox vaccine.
The firm's manufacturing plant in Kvistgard has been constructed and approved to fulfill the legal requirements for the handling of live micro-organisms, including genetically modified vaccines.
While Imvamune is classified as a Bio Safety Level-1 (BSL-1) vaccine, the company introduced its own additional requirements in the design and construction resulting in a facility that complies with the more restrictive BSL-2 regulations.
Bavarian Nordic has decided to place the fill and final treatment of its vaccines with its partner IDT, which operates a facility designated for filling, inspection, labelling and packaging of sterile vaccines.
Through this partnership, Bavarian Nordic claims it can produce, fill and finish more than 40m doses of Imvamune per year which, without significant investment, can be increased to 60m doses.
Imvamune is administered by injection, much like other modern vaccines today, rather than pricked into the skin with a bifurcated needle as is the case with traditional smallpox vaccines.
In recent pre-clinical trials Imvamune has been shown to generate an immune response in three to four days, faster than conventional vaccines which can take up to two weeks to trigger a response.
What is more, the vaccine virus contained in Imvamune does not proliferate in the body and therefore does not generate the post-vaccination complications associated with traditional smallpox vaccines.
Imvamune is based on a live non-replicating MVA-BN virus which is highly attenuated yet still capable to establish a potent immune response.
Vaccinia viruses re-engineered to express foreign genes are robust vectors for production of recombinant proteins, the most common being a vaccine delivery system for antigens.
Compared to replicating vaccinia viruses, MVA-BN provides similar or higher levels of recombinant gene expression even in non-permissive cells.
The replication of all other MVA strains in mammalian cell lines raises concerns regarding their safety, particularly if they were to be used to vaccinate people who are immune-compromised.
With MVA-BN however, the cell replication cycle is blocked at a very late stage which ensures that new viruses are not generated and released, so side-effects normally associated with replicating vaccinia viruses do not appear with MVA-BN.
The virus strain has been under development by Bavarian Nordic as both a safe smallpox vaccine and as the platform vector technology in the company's vaccine programmes against HIV, Dengue fever, Japanese encephalitis and cancer.
The company initiated three Phase II trials for Imvamune earlier this year, including a trial in HIV-infected persons with a more advanced stage of the disease, a second trial with healthy subjects, and a third trial in subjects with atopic dermatitis.
Bavarian Nordic's advanced clinical development programme has been further expedited by the US Food and Drug Administration's grant of fast-track status for Imvamune, the first-ever smallpox vaccine candidate to be given this designation.