Following closure of the main laboratory at its Pirbright site, the UK’s Institute for Animal Health is building a new high containment laboratory on the same site for much needed research into farm animal pathogens.
The Institute for Animal Health (IAH) in Surrey, UK has recently received the licence to begin work in a newly-built interim SAPO (Specified Animal Pathogens Order 1998) containment level 4 laboratory, known as IS4L for short. This allows the scientists working at the Institute to carry out research on farm animal pathogens that require the highest level of containment. These include foot-and-mouth disease, African swine fever and African horse sickness, among others.
IS4L has been put in place to allow work to continue following closure of the main laboratory at IAH’s Pirbright site, which is no longer suitable for high containment work. A new £100m high containment laboratory is currently being built on the same site and is expected to be ready in early 2014. Until then, IS4L has to be the workhorse of IAH’s high containment research.
Completed within a budget of £10m, which was provided by the UK Biotechnology and Biological Sciences Research Council (BBSRC) and the UK government’s Department for the Environment, Food and Rural Affairs (Defra), IS4L is an unusual building with very specialised use. Being able to work in this high-tech environment allows IAH to contribute significantly to economic and food security through the study of some of the world’s most important virus diseases of farm animals.
IAH is not just interested in existing pathogens, but also in being prepared for what might come next. According to Head of Estates and Engineering, Dr Michael Johnson, over the last 10 years 80% of all new pathogens that have affected humans arose out of animal populations. It seems likely that this process will continue to occur and IS4L provides the best facility available to be able to answer questions about the emergence of new diseases.
Over the last 10 years 80% of all new pathogens that have affected humans arose out of animal populations
Speaking about the new building, Dr Johnson said: “This means we can work on pathogens in a building that has multiple layers of protection from release of virus to the environment. It is important to have these very high engineering standards in this building. We have the highest level of control, the best seals, and in this building we’ve actually incorporated some world-leading design features.”
Layered approach
When thinking about containment of viruses in IS4L there are several principles in play. One is layering – there are multiple barriers designed to prevent virus from escaping. All virus work is carried out in primary containment, which can take the form of a glovebox or Class III Microbiological Safety Cabinet for the most dangerous of human pathogens. Class II microbiological safety cabinets are the standard primary containment for handling other viruses.
Combined with stringent laboratory procedures, this primary containment setup reduces the chances of virus escaping into a room to a very rare event. Rooms used for zoonotic viruses have an anteroom where laboratory clothing is changed.
IS4L has onion skin layers of containment thanks to progressively negative air pressure. The deeper into the building, the lower the pressure. This means that if any virus were to escape inside a room it would be arrested in the terminal HEPA filters in the room rather than leave the room via the door through which a worker would enter or exit. To support this, the building has an ingenious system of simple non-return dampers that stabilise the pressure cascade and seal if the airflow is lost.
The next important principle is air replacement, which at 15 times per hour is unlikely to impress a cleanroom specialist, but for virus control is a very high standard. There is HEPA filtration on incoming air and double HEPA filtration on outgoing air.
The airtight construction meets the most stringent requirements and the ventilation system is uniquely designed to offer a stable pressure regime in such an airtight building. The ventilation system is continuously monitored by an independent secondary system that prevents over-pressurisation, even if a fault occurs in the main control system.
This secondary pressure monitoring system shows in real time what is happening within the building. This is particularly powerful for spotting slow failures in the air pressure and filtration systems and so ensures the opportunity to intervene well before there is actually a risk of releasing virus to the environment.
The IS4L incorporates some unique design features developed at IAH, including drains that are continuously monitored for their integrity
According to Dr Uwe Mueller-Doblies, the IAH Biorisk Officer, IAH developed the secondary pressure monitoring system to address and overcome single points of failures identified in Hazard and Operability (HAZOP) studies of containment buildings that are inherent in conventional ventilation systems. This added layer of protection is unique for biocontainment facilities at IAH and, according to Dr Michael Johnson, is not used anywhere else.
Clearly it is not just a matter of ensuring airborne virus remains contained: laboratory waste must be dealt with and sometimes it is necessary to remove a piece of equipment or other materials from inside the contained area. The IS4L incorporates some unique design features developed at IAH, including drains that are continuously monitored for their integrity and a new barrier decontamination chamber that controls and logs gaseous decontamination process.
Specialised waste treatment
The drains that leave IS4L are specialised dual contained drains; wherever possible drains are inspectable; and between the laboratories and the effluent treatment plant effluent is transported in a pipe-in-pipe dual contained pipeline that is continuously monitored for potential leaks using pressurised fluorescent dye between the inner and outer pipe. Any drop in pressure immediately triggers the alarm and pipework can be investigated for potential leaks. The fluorescent dye allows the detection of very small leaks in the inner or outer wall of the pipe.
Decontamination of most items can be achieved using a simple and very familiar dunk tank. However, for certain equipment it would be impossible to do this. For example, to dispose of an old computer, the challenge would be to get formaldehyde or similar into every tiny convolution of the design. Instead IAH has installed autoclaves in IS4L that can double as decontamination chambers. These chambers expose equipment to gaseous decontamination with formaldehyde in alternation with vacuum pulses, so as to reach every possible corner in which a virus might hide. All rooms can be individually sealed for decontamination, such that work in the surrounding area can be continued.
The research that is going on in IS4L contributes to IAH’s overall science strategy, which aims to develop better control of viral diseases of livestock and poultry through improved understanding of how each virus causes disease; how the immune systems of farm animals respond to infections; and how viruses spread. This includes viruses that are carried by insects – midges that carry bluetongue virus, for example – and other arthropods, such as ticks. This knowledge enables the development of better ways to diagnose viral infections in farm animals, new and improved vaccines, and can help policy makers and farmers to decide on the most effective approaches to prevent and control outbreaks of diseases such as foot-and-mouth or bird flu.
The UK government and BBSRC have so far committed £200m to redevelopment of the IAH site in Pirbright
To support the world-class research going on at the Institute, the scientists and other staff need specialist modern facilities; the government and BBSRC have so far committed more than £200m to redevelopment of the IAH site in Pirbright, which will update and improve the Institute. IS4L is part of the first stage of redevelopment, which is costing in excess of £100m.
Minister for Universities and Science, David Willetts said: “The UK is a world leader in research into animal diseases, underpinned by the excellent work of BBSRC and the Institute for Animal Health. This significant investment in Pirbright will drive growth, create highly skilled jobs and improve our understanding of diseases that can have devastating effects on our rural economy. Not only is this vital for our agricultural industry but it also helps ensure future global food security.”
This significant investment in Pirbright will drive growth, create highly skilled jobs and improve our understanding of diseases that can have devastating effects on our rural economy
With a second phase of development that is currently in the planning stages, IAH will also be working on new lower containment laboratories and learning all the time about the latest in this specialist area of engineering. This next phase will add new facilities and supporting infrastructure for the work IAH does on diseases that affect poultry and other animals. The containment level 4 lab that will eventually house much of the work going on in IS4L is due to be finished early in 2014 and a second phase of development is expected to be complete in 2016.
