"The bottom line is, if you accept the money you need to adhere to all the regulations associated with it," says Stephanie Steppe, director of health science academic services and facilities at the University of Washington. "You need to think about those things before you ever apply for the grant."

Three years ago, the University of Washington applied to host the WWAMI Regional Center of Excellence (RCE) for Biodefense & Emerging Infectious Diseases Research, one of only eight in the country and the only one west of the Mississippi River. WWAMI refers to the five-state consortium including Washington, Wyoming, Alaska, Montana, and Idaho.

An RCE pulls together researchers who are working in emerging infectious diseases. Institutions draft joint operating agreements and submit a grant application to become an RCE. The University of Washington has joined forces with the universities of Montana, Idaho, and Alaska at Fairbanks; Seattle's Fred Hutchinson Cancer Research Center, Harborview Medical Center; the Institute for Systems Biology; the Veteran's Administration in Puget Sound; and the Rocky Mountain Laboratories in Montana, run by the NIH's National Institute of Allergy and Infectious Diseases.

"We created a think tank," says Steppe. "We each do research in our local labs and come together at least quarterly to exchange information.

"Many university faculty are doing research in a silo," she says. "They will have their own staff; they will have their own research expertise. When you are talking about Regional Centers, you need to think about collaboration versus competition."

In order to conduct key RCE research, a laboratory must meet federal qualifications to handle select agents, which are defined by the Centers for Disease Control's Select Agent Program as "biologic agents and toxins that pose a severe threat to public health and safety."

"We became an RCE two years ago, and the impact to the University of Washington by accepting the $50-million grant is extensive," says Steppe.

Substantial Upfront Investment

The University of Washington receives more federal grants and contracts than any other public institution in the United States, says Steppe, but even they were surprised by the process involved in becoming an RCE.

The first step in deciding whether or not to pursue one of these grants was to asses the state of their lab facilities. The University of Washington already has several separate BSL-3 laboratories, so it did not need to build new ones for the RCE. Steppe manages what she calls the "adventure" of a building containing three million gsf of space, with 13 separate fire zones. Of that, 7,000 asf are now designated for the RCE, including three BSL-3 labs and three BSL-2 labs, two animal labs, and various support spaces.

"There were researchers in those laboratories already that were not part of the RCE," she says. "We had to shift researchers around, which was not particularly pleasant, but we got through it."

It is also important to understand the level of administrative support this kind of research requires, cautions Steppe.

The University first organized a team to prepare the application. That team met almost weekly for three years to go over all the critical issues related to the RCE, first regarding the application, then implementing the grant, and eventually administering the RCE itself.

"Conservatively, we have spent $250,000 worth of salary not paid by the grant itself in order to make this program work," says Steppe. "Can your institution afford that?"

A large part of the administration is focused on complying with the complex laws regulating the biohazard industry, including the Anti-terrorism and Effective Death Penalty Act of 1996; the USA Patriot Act of 2001; the Public Health Security and Bioterrorism Preparedness Response Act of 2002; and, most significantly, 42CRF Parts 72 and 73—Possession, Use, and Transfer of Select Agents and Toxins.

Keeping an eye on all this is the designated Responsible Official (RO). In the case of the University of Washington, it is the director of environmental health and safety, who works with two alternates to assure compliance at all University facilities. Other institutions might appoint other individuals, such as the vice president of research, to fill this critical role. How that position is filled depends on the size and configuration of the institution, says Steppe.

"These ROs definitely take their job seriously," she says. "They personally face a potential $250,000 fine and five years in prison" for willful oversights and violations.

The RCE research process also must involve a concerted community outreach campaign. Steppe advises institutions to begin that campaign soon after applying for the grant, even before the application is funded.

"Responding to the community after the fact can be difficult and embarrassing for the institution, if the community feels the institution is keeping secrets. This gap in time allows a lot of unwarranted fears to come forth from the community," she says.

Satisfying Everyone

One frustration for the University has been determining appropriate processes to meet the expectations of many agencies with differing jurisdictions, such as the NIH, the Office of the Inspector General, the CDC, the FBI, the Department of Justice, and the U.S. Attorney General's Office. To aid in complying with these various issues, the University hired a consultant who specializes in certification of similar facilities. Many renovation costs were generated directly by the findings of the certifying agent, and the University spent close to $1 million satisfying all their infrastructure, security, and procedural requirements.

"Those facilities—which had been functioning as BSL-2 and BSL-3 laboratories and were being tested every year—were now defined as not functioning to the level that is appropriate for select agent research," says Steppe.

For example, one set of BSL-3 labs each contained local air conditioning units in the ceiling.

"The certifying agent saw them as 're-circulating air,' which was not literally true, but we requested modification to the HVAC system to satisfy that concern," says Steppe.

"Then the CDC inspectors told us to replace all the wooden casework with metal casework, but I found out later at a Tradeline conference that the CDC uses wooden casework in their own BSL-3 labs," she says. "The certifying agent also told us to take out the ping-pong indicators we used as a secondary visual back-up for negative air pressure, and it turns out that the ones we are removing are the same model that the CDC uses."

Steppe cautions institutions to weigh the decision about whether to hire a certifying agent or a commissioning agent. A certifying agent, who is normally less expensive to hire, will inspect a facility and point out a facility's inadequacies, but might not provide the detailed design necessary to rectify all the problems. A commissioning agent, on the other hand, might be worth the added expense because that company will help redesign or resolve any issues that arise during renovation and inspections.

Culture Shock

Security regulations regarding select agents can cause the most upheaval in an institution. The University of Washington already employed proximity card access and photo I.D.s in many of their facilities. Following a security assessment conducted by the CDC and the chief of the University's own police department, the system was enhanced with the addition of biometrics.

Every person working in a facility containing select agents—from the primary investigators to the custodial staff—must significantly modify their work activities.

The University used to be free to hire whomever it found qualified. Now anyone who has unsupervised access to the RCE must undergo an extensive FBI risk assessment and background check. Steppe says it took her four months to get clearance, while others may take as long as six months. Some people may never gain that access based solely on their country of origin, as stipulated by the USA Patriot Act, even if they have worked for the University for years.

"Universities have been known to return federal dollars because they do not want to deal with some of the aspects of the USA Patriot Act," says Steppe. "It could limit careers of individuals who might have come to your university from one of the seven countries listed in the Act."

Human resources must also be involved in developing procedures for these new employee questions and records that contain information about whether an individual is a convicted felon, has ever been dishonorably discharged from the military, or was institutionalized for mental reasons.

"Under current personnel guidelines, the supervisor cannot know this information about their employee, so it cannot be kept in the regular human resources file," explains Steppe. "We have had to develop an entirely new process for that paperwork, who has access to it, and who physically stores it."

Once hired, researchers need to be vigilant about following procedures for monitoring access privileges and handling select agents.

"Our faculty are having difficulty adjusting to that," says Steppe. "A university is all about free ideas, free access, and free movement. The ones who are part of the RCE recognize that they have to think about how they move through the corridors, who they talk to, and what they talk to them about. They are not working in secret, yet normal exchange of intellectual property is happening in a different environment. Some people buy into it; some people do not."

Administrators face additional paperwork and the same atmosphere of reticence. For example, building operating procedures that used to be kept only by the facilities managers must now be duplicated and kept in the RCE labs themselves.

The maintenance staff who will work in buildings containing select agents also must alter their procedures.

"They don't get to open the door with their set of grand master keys, walk in, change the light bulb, and walk out," says Steppe.

Obtaining FBI clearance for all maintenance, alterations, and custodial staff is not feasible, says Steppe. Instead, it makes more sense to establish procedures for escorting these critical workers whenever they need to be in the RCE. They are never left alone, and they never work after hours unless they are accompanied by an authorized individual. Guests and vendors must be escorted, as well, if they are to be in the labs at all.

You Never Work Alone

This heightened level of activity within the facility extends into the greater community. In addition to the police, the university must also ensure that they have a strong relationship with the local fire department and emergency medical personnel, while balancing the need for discretion with the need to share vital information.

"That is a conflict we continue to address each day as we interpret and reinterpret all of the regulations," says Steppe. "In the event of an emergency or release, there are a lot of people who are going to get involved very quickly."

That list includes the local emergency rooms.

"You don't just walk into your local ER and say, 'Hi, I'm from the Regional Center of Excellence. We are doing research with pestis,' and expect the emergency personnel to know what to do with an individual who has been exposed to pestis."

Undaunted by this process, the University of Washington has applied for a construction grant to build a Regional Biocontainment Laboratory (RBL), which would add further research and development components to the existing allergy and infectious diseases program. The NIH funds the construction of RBLs (with BSL-2 and BSL-3 capabilities), and National Biocontainment Laboratories (with BSL-4s) for research and training in biodefense and emerging infectious diseases. If approved, the project will require the University to build a $64-million facility with a $25-million NIH grant, $8.3 million from the University, and the rest from other sources. The University expects to hear in September if it has been approved for the grant.

By Lisa Wesel

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