Even a low-risk pathogen in the wrong hands can be very dangerous. People have died from African Horse Sickness because they have inhaled a freeze-dried virus preparation. Normally, the virus would never harm a human, but it can be deadly in the wrong configuration. The design must consider the range of pathogens and protocols that best suit each facility.

The Institute for Animal Health (IAH), a world leader for research on infectious diseases of livestock, operates sites in the United Kingdom, including Compton Laboratory in Berkshire that works on enzootic parasites, bacteria, and viruses with an emphasis on zoonoses; and the Pirbright Laboratory that works on exotic viruses and houses reference laboratories for the World Organization for Animal Health (OIE), the Food and Agricultural Organisation of the United Nations, and the EU Community Reference Laboratories, including the World Reference Lab for Foot and Mouth Disease.

“Our facilities are quite dated and the accommodations required for the animals require a giant overhead,” notes Uwe Ulex Mueller-Doblies, head of biosecurity at the IAH. “We were forced to come up with a strategy for new facilities where we can bring programs together, make them more efficient, and reduce our overhead costs.”

Discussing pathogen-inherent hazards must include information about host range, infectious dose, infection routes, regulatory and quality assurance requirements, pathogen inactivation profiles, pathogen tenacity, and whether they are exotic or endemic/enzootic. Protocol-inherent risks include aerosolization, primary containment constraints, contaminated equipment, pathogen inactivation steps, and material compatibility constraints.

Human health hazards, environmental contamination, and the risks of exposure to livestock must be considered when deciding what containment levels and types of barriers are necessary. Exposure risk levels determine the type of virus containment that is necessary.

The IAH uses a scale to show the risk levels and the type of containment required. The levels range from zero through four. The zero level pertains to amenity areas, such as where food is located, which must be hygienic and kept extremely clean. Exposure risk level one (ERL1) includes uninfected experimental laboratories where there is no work taking place with infectious viruses. At the ERL1 level, surfaces must be disinfected, as well.

Work taking place at the ERL2 involves standard low-risk work done in a Class II safety cabinet. Virus vials are open, but there is very little aerosolization and it is all contained in the cabinet.

There is a medium risk at ERL3 where primary containment is not feasible. Some of the work is done on an open bench, while some is done in the safety cabinet. ERL4 represents a challenge pertaining to areas, such as infected large animal rooms. At the ERL4 level, there is uncontrolled virus aerosol, which has to be enclosed in primary containment formed by a safety cabinet or an animal room.

“You have to nail down what is happening in each space so that everybody is on the same page because they have to accept that same risk,” notes Mueller-Doblies. “They are all taking a risk, but they have to accept it and that is the challenge to convey. Exposure risks must be matched to the working standards.”

The definitions of certain terms have to be agreed upon and clear to all employees working in a facility. “Containment zone” defines an area comprised of risk spaces, permitting unrestricted human involvement which is separated from other zones by a barrier. “Risk space” is a room or lab suite where the overall risk from the manipulation of a particular pathogen is managed through a common set of protocols. Barriers restrict human and material flow between containment zones.

If one assigns a pathogen to human health and an environmental hazard group, one can easily end up with 10 to 20 different containment requirements even in a relatively small facility. To reduce the complexity, five levels of risk spaces were created by the IAH, depending on what pathogens and what procedures are performed in certain areas of a facility. Risk space zero, or RS0, pertains to inside amenities, like a cafeteria, and do not require any personal protective clothing.

RS1 focuses on open-plan labs and lab coats are mandatory in these areas. RS2 pertains to labs with Class II biological safety cabinets and virus gowns and gloves are worn as protective equipment for virus handling procedures. RS3 involves labs with Class II or Class III safety cabinets and requires anyone entering the area to wear a gown, gloves, overshoes, and a face mask in the small animal and poultry areas, as well as PVC overalls in the large animal spaces. RS4 refers to labs with Class III or cabinet line safety cabinets. Gowns, gloves, and overshoes are required for RS4 small animal labs, while sealed positive-pressure suits are needed for RS4 large animal areas.

“We took the view that no lab is directly joined to a primary containment animal room,” says Mueller-Doblies. “It needs its own barrier to distinctly segregate primary and secondary containment spaces. The contamination challenge in a room housing loose animals is in orders of magnitude higher than in a laboratory, and a lot of laboratory equipment would not be fit for appropriate decontamination.”

T.C.