Biosafety Facilities: War on terror gives rise to new
Increased funding for research into treatments, antidotes and vaccines against bioterrorism agents has sparked a building boom for biosafety facilities
BY BETSY ZIOBRON
When we think of cleanrooms, we think of controlled manufacturing environments utilizing contamination control processes to remove small particles of dust and debris that can wreak havoc on circuitry and electronics. But the war on terror has given rise to a different type of "clean" facility where contamination control takes on a whole new meaning.
Following 9/11 and the subsequent anthrax attacks, increases in homeland security funding have given rise to Biosafety Level 3 (BSL-3) laboratories for clinical, diagnostic, research or production work with agents that may cause serious or potentially lethal disease. Much of the funding is channeled through the National Institute of Allergy and Infectious Diseases (NIAID) with at least a dozen BSL-3 facilities in planning or development stages at various universities throughout the nation.
In October 2003, a new BSL-3 lab opened in Los Alamos, N.M., and in May 2004, the Food Safety and Inspection Service (FSIS) opened a $1.65 million BSL-3 lab in Athens, Ga. "As part of our efforts to enhance homeland security, USDA has implemented an extensive program to secure American agricultural production and protect consumers," says Agriculture Secretary Ann M. Veneman regarding the Athens facility. "This new lab will enhance our surveillance program, while expanding our nation's capability to respond quickly to unforeseen events."
CDC scientist showers in a protective suite before leaving a Biosafety Level 4 laboratory in Atlanta, Georgia, USA. Source: CDC
As part of the antiterrorism infrastructure, President Bush signed the Project BioShield Act on July 21, 2004. Project BioShield is a $5.6 billion, 10-year program that expands both public- and private-sector research incentives to develop treatments, antidotes and vaccines against possible bioterrorism agents. This latest funding has sparked a building boom among public and private companies with proposals to build more than 35 new biosafety facilities. "Large commercial pharmaceutical companies were not interested in this work before because they couldn't make money working on vaccines and antidotes for diseases that don't even exist in our country," says Thomas R. Reynolds, executive vice president science and technology at Commonwealth Biotechnologies Inc. (CBI), which recently announced completion of its new BSL-3 virology lab. "But now that the government is funding this work through Project BioShield, I expect we'll see a lot more of it taking place in the commercial sector."
While biosafety labs are not classified as cleanrooms per se, both require strict policies and procedures and a unified commitment by everyone that enters. Accredited and audited by the Centers for Disease Control (CDC), biosafety laboratories range from BSL-1 to BSL-4, much like cleanrooms range from Class 10,000 to Class 1.
BSL-1 is suitable for work involving common agents not known to consistently cause disease in healthy adult humans. BSL-2 is similar to BSL-1 but involves agents of moderate potential hazard to personnel and the environment. BSL-3 involves agents that may cause serious or potentially lethal disease. A BSL-4 facility is required for work involving dangerous and exotic agents that pose a high risk of infection and life-threatening disease. "Diseases for which there is no medical treatment or cure are typically dealt with in a BSL-4 lab," says Reynolds. "Only a handful of BSL-4 facilities exist at well-guarded sites and bases throughout the country, many of which keep their location confidential." Workers in a BSL-4 lab are required to shower when leaving the facility.
Deborah Cannon of the CDC's Special Pathogens Branch processes SARS specimens. Photo by: James Gathany
The underlying difference between a biosafety lab and a cleanroom is the contamination focus. Where cleanrooms utilize contamination control to protect product, the use of contamination control practices in biosafety labs is to protect workers and prevent microorganisms from entering the environment. However, because it's imperative to achieve quality results in the lab, the experiments must also be protected from contamination.
"We utilize the principles of working in a cleanroom where the air must be pure with no environmental contaminants," says Reynolds. "While the typical cleanroom is concerned with contamination from oil, chemical, dust and debris, we need to prevent bacteria. Much of the work we perform is with tissue cultures, which is easily contaminated by bacteria." Techniques deployed in the biosafety lab to ensure quality results include antibiotics in the medium, filtration, sterilization and basic decontamination practices.
Like a cleanroom environment, the main piece of contamination equipment is the exhaust hood using HEPA filtration. Class II, type B biological safety fume hoods utilize double HEPA filters and vent 100 percent of the air entering the hood to the outside of the building. These exhaust systems are typically completely isolated from the rest of the facility, and the air is never recycled.
In the biosafety lab, autoclaves are used to sterilize equipment and biological waste. "Nothing is removed from the BSL-3 lab that has not been autoclaved," says Reynolds. "There's nothing that the autoclave can't sterilize, and we test for that by autoclaving test containers and then ensuring that they can no longer be cultured." Once biological waste is autoclaved, a haz-mat collection group properly removes it from the premises.
"We conduct surface decontamination on a daily basis and on anything coming in and out of the laboratory," says Reynolds. "It is very much like a typical cleanroom in that everything is done under extremely strict guidelines using a standard operating procedure that includes both a safety manual and a quality manual."
Like those in cleanroom environments, workers in the biosafety lab are required to wear protective clothing, including sterile disposable gowns that cover the entire body, gloves, eye protection and, in some cases, respirators. Passage to the laboratory is through a series of two self-closing doors, and the sterile passageway often includes a clothes change room where workers dress in and out. The disposable clothing is autoclaved along with other biological waste.
"We're interested in keeping people safe, and the people that work in our BSL-3 facility come here because they want to do this type of work—it is their intellectual interest," says Reynolds. "It's really no different than the risks faced by emergency room physicians on a daily basis, and we take the necessary precautions to protect ourselves."
Personnel working in the BSL-3 lab are often vaccinated against the very disease-causing agent they are working with, and all are scientifically well versed in the characteristics of the organisms. The CDC monitors the number of lab-transmitted diseases each year, but cases are rare. "We've never had anyone become infected at our facility, and that's partly due to having extremely good safety practices," says Reynolds. "We have a medical monitoring program through the nearby hospital for all of our workers." CBI's medical monitoring program includes having local doctors aware of the various organisms and infectious diseases being worked on and who are responsible for administering vaccines. Each worker is monitored regularly by the doctors and whenever sickness occurs.
Other requirements of a BSL-3 lab include security and limited access with key cards, hand washing and safe handling requirements, insect and rodent control, hazard warning signs, construction that allows easy cleaning and decontamination, eyewash stations, showers and thorough documentation.
"This is good work we're doing here. It's an opportunity to make an impact, and it's patriotic," says Reynolds. "If you're a scientist interested in pathogenic organisms, why not do work that provides some good for our country and the world?"
Work in progress
A 45-person company, CBI was established in 1992. The company built its first BSL-3 laboratory in 1997, and began working with pathogenic agents in 2000. In July 2004, they completed a new virology BSL-3 laboratory commensurate with the start of two contracts for the production of select agent viruses and assay of clinical samples stemming from a human trial of a vaccine targeting a select agent virus. "By expanding our facility to include a virology BSL-3 lab in addition to a bacteriology lab, we are now able to separate functions," explains Reynolds. "Viruses and bacteria are handled differently. Previously with one lab, we had to decontaminate in order to start virology work. Now we perform both types of work simultaneously."
CBI currently has biodefense contracts with both federal agencies and private companies involving analyses for select agent pathogens, detection of bioagents, including ricin and anthrax samples taken from mail sorting facilities, and vaccine development. CBI has also teamed up with DynPort Vaccine Company LLC, which is responsible for developing many of the vaccines for select agents. "We're working in vaccine development by providing tests for human clinical trials that determine vaccination response," explains Reynolds. "In order to accept human samples, our BSL-3 lab must also operate under CLIA." CLIA is the Clinical Laboratory Improvement Amendments through which all lab testing performed on humans in the U.S. is regulated. "We have the capabilities to do a lot of different things, and our reputation in biodefense is now well established," says Reynolds. "Because we are for-profit and small, we have the ability to get work done quickly and cost efficiently."
A scientist wearing a protective suit with helmet and face mask is seated at a biological safety fume hood as he conducts his studies. Photo by: James Gathany
CBI also recently announced that it has initiated the sale of biodefense reagents. Under previous contracts from DynPort, CBI developed methods of expression and purification of proteins associated with select agent pathogens and antibodies directed against those same proteins. Under license from DynPort, CBI is producing and selling these proteins and antibodies to investigators in the biodefense community. "CBI has been working steadily towards this product line for the past year, ever since our first production contract from DynPort," says Robert B. Harris, Ph.D., president and CEO. "It is essential that investigators in biodefense related work have access to all the necessary reagents and that these investigators work with common reagents so that the scientific community can evaluate the results."
One of the few public for-profit companies involved in bioterrorism defense work, CBI foresees many more contracts and laboratory expansion in the future. "There's a lot of funding, and we're hoping for a small portion of that. Having the new virology lab is key to making us more attractive to new potential clients," says Reynolds. "There's a growing demand in the biodefense sector for these services, and we're planning a further expansion of the BSL-3 suite to include a production bacteriology laboratory."
With the funding available, we can expect to see many more of these "clean" biosafety laboratories popping up around the country. Unfortunately, the times we live in call for this type of work, but it's work that is vital to maintaining our country's safety, defense and freedom.
The following resources provide more information on biosafety labs:
- Commonwealth Biotechnologies Inc., www.cbi-biotech.com
- Biosafety in Biomedical and Microbiological Laboratories 4th Edition, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, and National Institutes of Health. Available at http://bmbl.od.nih.gov.
- Biodefense Program, National Institute of Allergy and Infectious Diseases, www.niaid.nih.gov
- Centers for Disease Control and Prevention, www.cdc.gov.