Analysis: vaccine production: Biosecurity measures in handling live viruses must be followed to the letter, writes Dr Seamus Lennon
Evidence at present indicates that the outbreak of foot-and-mouth disease in England may have originated either in a nearby facility that manufactures a vaccine against this highly contagious disease or from the adjacent government-run Pirbright research laboratory.
The vaccine facility is operated by Merial, which is a joint venture between two major pharmaceutical companies - Merck and Sanofi Avensis. Merial hold a license issued by the UK authorities to manufacture a vaccine against foot-and-mouth disease.
The manufacture of a virus vaccine is a high-risk activity and involves using live virus material. Thus, any such facility must have in place a range of measures aimed at preventing any escape of virus.
This is especially true where the virus being handled is an exotic virus - ie not normally found in that country. In these situations, the control measures for the use of such a virus are even more stringent.
The classical production method for a virus vaccine is to firstly grow the virus up to a sufficiently large scale. Viruses are grown by infecting cultured animal cells with a small volume of virus, and this mix is then incubated for a number of days. The virus invades an animal cell, replicates, and releases virus particles which infect more cells, and so on. At the end of the incubation period, the culture vessel will contain dead animal cells and millions of live virus particles. This fluid is harvested, clarified and the virus is then killed or inactivated using a suitable chemical. This inactivated virus material can then be used to produce a vaccine.
The entire production process can take three to four weeks, and there are many stages during the process that involve handling live virus. Furthermore, a separate quality control laboratory will test to ensure the purity and potency of the vaccine, and these procedures also necessitate the use of live virus material.
The operation of a vaccine manufacturing facility is subject to EU guidelines, and each facility is regularly inspected by the relevant competent authority to ensure compliance with these guidelines. Similar controls are used by research labs that use exotic viruses.
A company must take numerous precautions to prevent the escape of virus from their facility. For example, all employees would don a company uniform when entering the facility, and this uniform would never leave the facility - laundering facilities would be located on site.
Before working with the virus, a further disposable sterile uniform is put on, and workers would shower after working with live virus. Everything that comes into contact with virus - the sterile uniform, containers, etc - is sterilised using steam sterilisation before being removed from the facility.
The building itself is designed to block the escape of the virus. The virus is only handled within a special cabinet designed to contain all air, and this cabinet itself is located in a room which operates at negative air pressure - ensuring that no air escapes from the room.
All exhaust air from the cabinet and the room is filtered at least twice through specially designed filters before it leaves the facility.
All waste water is also sterilised before it is released to sewer. All rooms where live virus is used are cleaned with special disinfectants regularly and may also be fumigated using formaldehyde.
All the above controls also serve another important requirement: to maintain a sterile production facility and hence ensure that no bacteria or extraneous viruses contaminate the production process. Similar controls would also exist in the quality control facility.
Despite all the above checks in place, it appears that some control broke down that resulted in the escape of live virus from the facility.
The most likely cause of such a breakdown in biosecurity is human - the failure to follow procedures to the letter.
Alternatively, equipment failure is often linked to biosecurity problems: for example, a leak could develop in a filter normally designed to prevent transmission of virus.
While guidelines call for frequent testing of all equipment, problems can arise with equipment which are not immediately apparent to personnel.
A review of all biosecurity measures is currently under way at the Merial and Pirbright facilities, and this review may identify the possible source of the virus release. However, due to the complexity of the processes involved, it may be that the actual source is never identified.
In recent years the incidence of accidental foot-and-mouth virus release from a research or vaccine-manufacturing facility has been rare, with only one case reported since 1990 - when a foot-and-mouth outbreak in Russia in 1993 was linked to a research institute that handled the live virus.
More frequently, biosecurity lapses occur from the outside environment into the facility. For example, a vaccine manufacturing facility operated by Chiron in Liverpool was closed in 2004 due to bacterial contamination of the vaccine product.
There is one other biosecurity measure which is used in the United States. There the use of foot-and-mouth virus, along with other exotic viruses, is restricted to the Plum Island research facility, which is two miles off the far eastern tip of Long Island, New York. This ensures that a large safety cordon exists should any virus accidentally be released from that facility.
• Dr Seamus Lennonis head of the Department of Life and Physical Sciences in the Galway Mayo Institute of Technology and previously worked in a number of vaccine manufacturing facilities.