5

PATHS FROM ASSESSMENTS TO FUNCTIONAL LABS (BREAKOUT SESSIONS)

While the Chapter 3 examined assessments broadly, this session provided specific examples of the process by which countries and corporations decide where and when to build labs, the degree to which their original objectives have been achieved, and the lessons they have learned from their experiences.

In order to inform discussions, each breakout session started with several short talks highlighting containment lab facilities in one geographic region. Each speaker focused mainly on a single lab and described that lab’s strengths, ongoing efforts to sustain and improve capabilities, and key obstacles that had been successfully overcome. Topics discussed included how well each lab is fulfilling its original research and public health goals; where each lab is situated within country and regional networks; whether initial and on-going costs and funding have been as expected; and ongoing laboratory biosafety, biosecurity, and maintenance efforts.

During the discussions, participants in each breakout session were asked to consider a number of questions about the accuracy and completeness of the original needs assessment:

1.   How well are labs fulfilling their original research and public health goals?

2.   Did design, construction, and commissioning proceed as expected? Did the initial assessments consider all the relevant issues? How were difficulties overcome? With the benefit of hindsight, what could have been done differently?

3.   Are costs as expected? Was initial and on-going funding as expected? How involved are donors? How are labs affecting the local economy?

4.   How well are labs recruiting and retaining qualified scientific and engineering staff?

5.   What steps are labs taking to provide the desired levels of biosafety and biosecurity?

6.   How are local communities receiving labs?

BREAKOUT SESSION 1: EASTERN ASIA
Chair: Leila dos Santos Macedo
Rapporteur: Fran Sharples

Leila dos Santos Macedo (Brazilian Biosafety Association [ANBio], Brazil) opened the session by reiterating the observation from earlier sessions that East Asia is a hotbed of emerging and re-emerging infectious diseases. Participants then heard talks describing labs in South Korea and Thailand.

BREAKOUT SESSION PRESENTATIONS

Meeting International Biosafety and Biocontainment Standards in Low-resource Settings: The Southeast Asian Experience

Stuart Blacksell (Mahidol Oxford Tropical Medicine Research Unit [MORU]) described challenges MORU has experienced in Southeast Asia.



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5 PATHS FROM ASSESSMENTS TO FUNCTIONAL LABS (BREAKOUT SESSIONS) While the Chapter 3 examined assessments broadly, this session provided specific examples of the process by which countries and corporations decide where and when to build labs, the degree to which their original objectives have been achieved, and the lessons they have learned from their experiences. In order to inform discussions, each breakout session started with several short talks highlighting containment lab facilities in one geographic region. Each speaker focused mainly on a single lab and described that lab’s strengths, ongoing efforts to sustain and improve capabilities, and key obstacles that had been successfully overcome. Topics discussed included how well each lab is fulfilling its original research and public health goals; where each lab is situated within country and regional networks; whether initial and on-going costs and funding have been as expected; and ongoing laboratory biosafety, biosecurity, and maintenance efforts. During the discussions, participants in each breakout session were asked to consider a number of questions about the accuracy and completeness of the original needs assessment: 1. How well are labs fulfilling their original research and public health goals? 2. Did design, construction, and commissioning proceed as expected? Did the initial assessments consider all the relevant issues? How were difficulties overcome? With the benefit of hindsight, what could have been done differently? 3. Are costs as expected? Was initial and on-going funding as expected? How involved are donors? How are labs affecting the local economy? 4. How well are labs recruiting and retaining qualified scientific and engineering staff? 5. What steps are labs taking to provide the desired levels of biosafety and biosecurity? 6. How are local communities receiving labs? BREAKOUT SESSION 1: EASTERN ASIA Chair: Leila dos Santos Macedo Rapporteur: Fran Sharples Leila dos Santos Macedo (Brazilian Biosafety Association [ANBio], Brazil) opened the session by reiterating the observation from earlier sessions that East Asia is a hotbed of emerging and re-emerging infectious diseases. Participants then heard talks describing labs in South Korea and Thailand. BREAKOUT SESSION PRESENTATIONS Meeting International Biosafety and Biocontainment Standards in Low-resource Settings: The Southeast Asian Experience Stuart Blacksell (Mahidol Oxford Tropical Medicine Research Unit [MORU]) described challenges MORU has experienced in Southeast Asia. 39

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40 Biosecurity Challenges Dr. Blacksell started by noting that the world’s population is concentrated in Southeast Asia and that newly emerging diseases (e.g., severe acute respiratory syndrome [SARS] and Nipah), agents of increased virulence (e.g., avian influenza and tuberculosis), and endemic diseases caused by risk group 3 agents drive the region’s diagnostic and research needs. While Southeast Asia has at least 45 BSL-3 labs, Dr. Blacksell explained that running a facility responsibly requires a huge investment of time, people, facilities, and money, and questions exist about standards, management, training, and security for most labs in the region. As an example of the challenges, Dr. Blacksell described his experiences with MORU, which maintains a regional network of field sites and BSL-2 and BSL-3 labs. MORU recently built new labs in Bangkok, Thailand and Vientane, Laos and has three additional labs in Thailand as well as labs in Cambodia and Bangladesh. Historically, the area has lacked a safety culture, so MORU requires a robust induction procedure and documents all training and the resulting competencies of its employees. For its training, MORU utilizes consultants, the United States Department of State Biosecurity Engagement Program (BEP), Sandia National Laboratories, the World Health Organization (WHO), and the Australian Government Overseas Aid Program (AusAID). Training includes dual-use awareness, and labs hold regular refresher training. MORU employs a full time Biosafety Administrator, a 50 percent time Registered Biosafety Professional, and seven biosafety site representatives. To help address the severe regional lack of biosafety experience and fill the required positions, MORU formed a regional twinning partnership with the Australian Animal Health Laboratory. Dr. Blacksell stated that security is a concern and that each lab has a site-specific security plan. Because the lab’s funding includes U.S. money, to obtain access, staff must pass a United States Federal Bureau of Investigation security risk assessment and be a United States Department of Justice ”registered entity.” Where possible (i.e., Thailand), local police also check all staff using national and international databases. In additional to personnel checks, the labs have also invested in physical security. BSL-3 freezers require fingerprint access, and access is restricted to three people; incubators with BSL-3 organisms use coded locks. Additionally, MORU has catalogued 20,000 freezer samples, documenting agent, source, intended use, and quantity using software that creates an audit trail. Audits are conducted every three months. While South Korea and Singapore and to a lesser extent Thailand have well-developed laws governing the safe and secure operation of biocontainment facilities, he observed that most countries in the region either lack national biosafety legislation or have laws that are poorly enforced and understood. MORU is required to follow the host country’s local laws, United Kingdom rules because of their Oxford University affiliation, and Biosafety in Microbiological and Biomedical Laboratories (BMBL) guidelines and United States Select Agent rules to obtain access to U.S. funds. He elaborated that earning Select Agent qualification turned out to be a bigger task than initially expected but that it was ultimately worthwhile both because of the resulting access to funds and because it gave them added confidence in their operation. The application process, which made them examine everything they did, ultimately resulted in good databases, emergency response procedures, and standard operating procedures (SOP) in both English and Thai. Other challenges include mismanagement, finding local services and resources, and limited budgets, particularly for maintenance and training. Additionally, the tropical climate makes it very wasteful to cool and dry air only to ultimately pump it back outside; he suggested that regulators consider allowing recirculation of 85 percent of the air with additional high- efficiency particulate air (HEPA) filtration. Given the complexity of running BSL-3 labs in the area, Dr. Blacksell encouraged people considering new labs to accurately assess their initial expenses, anticipated operational and

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41 Paths from Assessments to Functional Labs maintenance costs, and the associated biosafety and biosecurity risks to determine if a BSL-3 is truly needed or if a BSL-2 with BSL-3 practices might be sufficient to meet their needs. Operating a BSL-3 Facility in Korea: The IVI Experience Soh Jin Lee (International Vaccine Institute [IVI], South Korea) discussed the history and operations of IVI’s BSL-3 facility. IVI is a non-profit, international organization, headquartered in Seoul, South Korea that was created under the auspices of the United Nations Development Program. IVI’s mission is to improve the health of people in developing countries by the development, introduction, and use of new and improved vaccines. Ms. Lee explained that IVI’s BSL-3+ project, which consists of 350 m2 of animal biosafety level (ABSL) -3 and BSL-3 areas, was funded by the South Korean government and was initiated in 2005 before most of the current Korean regulations were passed. Construction started in 2007, and the facility was certified using international standards in 2008. The facility was recertified by the Korean Center for Disease Control and Prevention (KCDC) in 2009. Like the other 19 certified BSL-3 facilities in Korea, IVI requires an annual inspection that includes a shutdown, general decontamination, and new training. IVI also requires reaccreditation every three years by the KCDC. IVI operates in compliance with all relevant Korean laws including the Act on the Prevention and Control of Infectious Diseases, which includes a pathogen tracking system and a list of pathogens under the control of the KCDC; the Act on the Prohibition of Biological or Chemical Weapons and the Control of the Production, Export, and Import of Special Biological or Chemical Agents; the Living Modified Organism Regulations; and the Act on Transnational Transportation of Living Modified Organisms. IVI also has its own internal BSL-3 management system, manuals, SOPs, and training practices. For example, approval of the Institutional Biosafety Committee is required before changing experimental protocols or using new animals or infectious materials, and the General Manager must authorize all new facility users. BSL-3 training is provided to scientists, research assistants, maintenance engineers, and institutional safety committee members. The goal of the training is to give people the confidence and skills to create a safe work environment. The training includes biosafety lectures and general information on biosecurity. It also includes theoretical and practical training on BSL-3 operations, cleaning and decontamination, animal handling, equipment usage, and emergency procedures. The facility is monitored using closed circuit television and an automatic central monitoring system that notifies the appropriate people by text message in the event of an emergency. Biocontainment for Clinical and Research Activities Sunee Sirivichayakul (Chulalongkorn University, Thailand) presented the goals and policies of the Central Biocontainment Lab, which is located in Bangkok, Thailand and is part of Chulalongkorn University and the Thai Red Cross Society. The BSL-3 facility, which has operated since Thailand’s 2008 bird flu epidemic, strives to provide a safe environment for working with biological agents. The facility is particularly interested in agents that threaten national security due to the ease of their transmission or dissemination, high mortality rates, potential for a major public health impact, potential for public panic and social disruption, or requirements for special action for public health preparedness. Dr. Sirivichayakul noted that the lab widely solicits proposals for work and has a number of attractive features including a review group of at least five knowledgeable committee members, one full-time staffer who cares for the facility and its equipment, regular maintenance, and training for new users. Facility rules dictate that no more than three people may work in the

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42 Biosecurity Challenges lab simultaneously, and if only one person is working in the BSL-3, then a second person must be available outside in case of emergency. She observed that one key challenge for the laboratory has been its high operational and maintenance costs, which exist even during those times when the facilities are not heavily used. So far, the Faculty of Medicine has provided funding, and individual users help by bearing the cost of disposable items such as N95 respirators and gowns. BREAKOUT SESSION 2: AFRICA Chair: Michael Ugrumov Rapporteur: Benjamin Rusek This session comprised presentations from three labs in African countries. Two are located in North Africa and one Central Africa, a hotbed for emerging infectious diseases. Although all three are in developing countries, all are well funded through a combination of federal sponsorships, international partnerships, and corporate support. While all engage in research and disease surveillance, the primary function of two of the labs is vaccine production. Following the talks, Michael Ugrumov (Institute of Developmental Biology, Russian Academy of Sciences, Russia) led a discussion between the speakers and the audience on issues introduced during the talks. BREAKOUT SESSION SPRESENTATIONS Biopharma’s Vaccine and Diagnostics Production in Morocco: Current Situation and Future Changes Mehdi El Harrak (Biopharma) described Biopharma’s facilities and capabilities and the role of vaccine production in security. Dr. El Harrak started by explaining that North Africa is a homogeneous epidemiological area and is constantly at risk for the introduction of exotic diseases. The state laboratory Biopharma was created in 1984 to serve as a national center of biotechnology. In that capacity, the facility develops diagnostics for local diseases, performs active surveillance that plays a strategic role in providing early warnings and controlling epidemics, and produces 90% of the vaccines for national veterinary prophylactic campaigns as well as for the private sector and for export. Production techniques include bacterial fermentation, production on specific pathogen- free eggs, conventional cell culture, and suspension cell culture. Biopharma maintains BSL-3 labs that serve a variety of functions: bacterial fermentation, viral vaccine production, quality control, research and development, and animal housing. Dr. El Harrak noted several examples of his facility’s work: • Biopharma developed a live attenuated vaccine for African horse sickness that successfully eliminated the disease locally. • In addition to supplying national prophylactic campaigns against sheep and goat pox, Biopharma has also supplied vaccine campaigns in Libya and Tunisia. Many of the 15 - 25 million vaccine doses produced annually are exported to other African and Middle Eastern countries. • An inactivated camel pox vaccine developed by Biopharma from a local strain has been used in Morocco, Western Sahara, Algeria, Tunisia, Libya, Mauritania, and the Middle East.

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43 Paths from Assessments to Functional Labs • In collaboration with WHO and the Institut Pasteur, Biopharma is developing an inactivated rabies vaccine for a national rabies eradication program. The program aims to vaccinate 70 percent of the dog population, which acts as the vector and reservoir for rabies in North Africa. • Biopharma stockpiles the equivalent of 2 million bovine doses of foot and mouth disease (FMD) vaccine as a concentrated, inactivated antigen that could be manufactured within 48 hours. While Morocco has been free from FMD without vaccination since 2006, Biopharma performs large serological surveys and looks for evidence of FMD virus circulation using enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) tests. • Biopharma stores a national collection of cells, bacteria, and viruses and conducts active surveillance of circulating strains for many diseases to ensure correct vaccine formulations. Dr. El Harrak then described some of Biopharma’s constraints. Many laboratories are in old buildings that require structural improvement. For example, many use centralized rather than terminal HEPA filters, and fluid distribution and waste treatment systems are in poor condition. Also, the facility itself is currently located in a residential area inconsistent with the risk associated with its activities and biosecurity requirements. Biopharma plans to move and build a new laboratory according to international good manufacturing practice (GMP) standards. The new facility will have 1,850 m2; 1,330 m2; and 400 m2 of BSL-3, BSL-2, and clean room space, respectively. Biopharma is also trying to become a World Organisation for Animal Health (OIE) Reference Laboratory for bluetongue disease, sheep pox, African horse sickness, and peste des petits ruminants. Veterinary Serum and Vaccine Research Institute in Egypt: Present and Future Prospects Seham El-Zeedy (Veterinary Serum and Vaccine Research Institute [VSVRI], Egypt) described the past, current, and future efforts of VSVRI to improve animal health in Egypt. Dr. El-Zeedy started her presentation by explaining that VSVRI was established in the Abbassia district of east Cairo in 1903 to produce vaccines and antisera to protect cattle against rinderpest. Since its founding, VSVRI’s mission and facilities have expanded, and the institute now has multiple goals: producing highly effective veterinary vaccines, sera, and diagnostic reagents using both reference and local isolates; producing cost-effective combination vaccines; and conducting research for improved veterinary vaccines, sera, and diagnostic reagents. VSVRI currently produces both live and inactivated vaccines for large animals and poultry as well as a number of antigens and sera. Overall, the facility has over 600 workers including a research team of more than 200 that studies both viral and bacterial pathogens. VSVRI cooperates with the United States Naval Medical Research Unit 3, the United States Biosecurity Engagement Program (BEP), the Food and Agriculture Organization of the United Nations (FAO), OIE, and WHO. She also said that VSVRI uses standard design principles for safety and security. The facilities include primary containment barriers that protect workers from the agents (e.g., gloves, gowns, masks, biological safety cabinets [BSCs], and vaccines), secondary containment barriers that separate the agents and the outside environment (e.g., air tight rooms, showers, sewage treatment, and proper waste disposal), and tertiary containment barriers (e.g., walls, fences, security, and quarantine rules). In the future, Dr. El-Zeedy would like to see increased use of molecular biology for improving vaccines and diagnostic reagents; more innovative veterinary vaccines, sera, and diagnostic reagents; and expanded training on current technologies. Her plans call for the production facilities to be certified according to GMP requirements for veterinary vaccine

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44 Biosecurity Challenges production, and she also expects on-going upgrades to convert an existing laboratory to BSL-3 standards to be completed soon. The new BSL-3 facility is being built in response to Egypt’s avian influenza (AI) outbreaks. Egypt’s first highly pathogenic avian influenza (HPAI) outbreak was announced in February 2007, and the country began vaccination in March 2007 using imported inactivated H5N1 and H5N2 vaccines. As the disease is now endemic and controlling poultry outbreaks is the key to preventing human AI infections, she explained that Egypt needs a national laboratory that can produce vaccines effective against the local AI strains. To meet this need, VSVRI is upgrading an existing laboratory to BSL-3 standards to create the appropriate protection for working with HPAI. The new laboratory will also manufacture FMD vaccine. In preparation for the new BSL-3 facility, VSVRI is developing a training program that will ensure that all personnel meet institutional expectations for working in high-containment labs. In general, all personnel entering the containment facility will receive job-specific training prior to starting work, and all training will be documented. The International Centre of Medical Research of Franceville: A Medical Research Center in the Heart of a Tropical Rainforest Jean-Paul Gonzalez (International Centre of Medical Research of Franceville [CIRMF], Gabon/France) described the history of CIRMF and the work the facility’s unique location makes possible. Dr. Gonzalez started by relaying the history of the CIRMF, which was founded by Omar Bongo, the President of Gabon, in 1974. The facility, which covers 98 acres, became operational in 1979 and added a BSL-3 lab in 1982 for HIV studies. Animal biosafety level (ABSL) -3 primate containment structures followed in 1985, and a BSL-3+ was developed in 1996 to facilitate Ebola research after Ebola outbreaks in Gabon. In 2011 CIRMF began operating a unique BSL-4 glove box1 whose mission is to diagnose and characterize BSL-4 agents on a regional level. Altogether, CIRMF currently has 60 scientists, 1,500 m2 of labs, 2 field stations, a primate center with 450 apes, and living accommodations for scientists on site. It receives funding from the Gabonese government (20 percent), the oil company TOTAL- GABON (65 percent), the French Ministry of Foreign and European Affairs (10 percent), and international institutions (5 percent). Dr. Gonzalez described the work of several of CIRMF’s seven research units: emerging viral diseases, retrovirology, medical parasitology, health ecology, sickle cell disease, medical biology and public health, and primatology. The emerging viral diseases research unit, for example, studies viral biodiversity of the Central African tropical rainforest, the emergence of human viral diseases, and the fundamentals of cross-species transmission. Past work examined the phylogeny and natural history of Ebola, suggesting that fruit bats serve as a reservoir for the virus and then infect both great apes and humans. Work also investigated asymptomatic infections and deep immunosuppression caused by the virus. Research tools and methods include molecular virology, in vivo immunology, human cohort studies, animal trapping, entomology, and field investigations. In general, CIRMF’s field investigations survey 1 Adding to the confusion is the range of design options used in building such facilities. For instance, the maximum containment labs may be self-contained suites accessed through airlocks and decontaminating showers by researchers wearing one-piece, positive-pressure suits with their own life-support systems. On the other hand, some BSL-4 labs may consist of little more than small glove box isolators in which researchers access samples through glove-enclosed portals.See: http://www.engineering.com/Library/ArticlesPage/tabid/85/articleType/ArticleView/articleId/92/Level-4- Containment-Labs.aspx

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45 Paths from Assessments to Functional Labs both of the nearby ecosystems (tropical rainforest and savannah), as each environment has unique pathogens and diseases. Dr. Gonzalez also highlighted the work of the retrovirology unit and the primate center. The retrovirology unit, which uses BSL-3 facilities, has worked on human immunodeficiency virus (HIV) diagnostics and genotyping, simian immunodeficiency virus (SIV) phylogeny and transmission, retrovirus discovery and characterization, and antiviral drug testing. The primate center, whose facilities include an ABSL-3 lab and a surgery room, has studied anti-HIV drug therapies, characterized the physiopathology of SIV in Mandrill monkeys, and developed a vaccine against Chikungunya virus using macaques. Dr. Gonzalez provided additional information about CIRMF during the session on BSL-4 labs (Chapter 8). BREAKOUT SESSION 3: EASTERN EUROPE AND WESTERN ASIA Chair: Greg Smith Rapporteur: Alison Hottes In this session, participants heard talks about containment labs in various stages of their life cycles. Two of the labs have long histories; one is rejuvenating containment facilities that have existed since the lab’s founding, while the other is in the last stage of adding BSL-3 facilities. The other two presentations described new labs being built through collaborations between the host country and a foreign partner to address specific regional needs. One is nearing certification, and the other is stalled in the last portion of the design stage. Greg Smith (Commonwealth Scientific and Industrial Research Organisation, Australian Animal Health Lab, Australia), the session chair, then led a discussion that elaborated on issues introduced during the talks. BREAKOUT SESSION PRESENTATIONS Georgian Central Public Health Reference Laboratory Colonel Arthur Lyons (United States Army Medical Research and Materiel Command, United States) described the mission and facilities of the Georgian Central Public Health Reference Laboratory (CPHRL) and shared lessons learned from each stage of the development process. Colonel Lyons explained that CPHRL, which is a collaboration and partnership between the United States and the Republic of Georgia, seeks to promote public and animal health through infectious disease detection, epidemiological surveillance, and research for the benefit of Georgia, the Caucasus region, and the global community. CPHRL will augment current surveillance and diagnostics initiatives with BSL-3 facilities, genomics capabilities, and a vivarium; serve as the hub of a Central Asia regional network; and engage in research on bacteriophages, wound healing, and vector-borne diseases. CPHRL will focus on capacity building and will collaborate with both national and international partners including the National Center for Disease Control and Public Health; the Laboratory of the Ministry of Agriculture; the George Eliava Institute of Bacteriophage, Microbiology, and Virology; the United States Centers for Disease Control and Prevention (CDC), and the World Health Organization (WHO). Colonel Lyons reported that Georgia and the United States broke ground in 2004, completed construction in 2010, and hope to certify the lab by the end of the 2011. The building (7,500 m2 including 2,500 m2 of lab space) contains two separate BSL-3 laboratory suites: one for animal pathogens and one for human pathogens. The human pathogen lab contains animal-

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46 Biosecurity Challenges holding rooms that can operate at either BSL-2 or BSL-3 levels. The facility also contains BSL- 2 space, a BSL-2 laboratory training suite, and cell culture and media preparation rooms. The surrounding area includes a perimeter fence, an incinerator building, fuel tanks, water tanks, and a natural gas line. The United States Army Medical Research and Materiel Command expects to occupy a portion of CPHRL permanently as a guest of the government of Georgia, and the United States will bring in experts to train Georgians to both establish and maintain operations. Colonel Lyons then shared lessons learned from each stage in the process. He feels that during the planning and coordination stage it is important to: • Obtain political buy-in and involve the appropriate political level, as ultimately, Ministers and politicians will need to budget for the lab and defend it publicly; • Obtain scientific buy-in and have the right partner country scientific personnel begin planning the scientific work and continue planning throughout the construction process to facilitate a quick start-up upon completion; and • Consider starting public awareness outreach. During the design phase, Colonel Lyons recommended the following: • Engage a commissioning agent (preferably 3rd party). • Document the Basis of Design and describe why and when decisions were made; this will help the project team make good decisions during construction. • Realize that personnel changes within program offices and the partner nation government will complicate the task. • Perform a comprehensive utility study. • Design for sustainability, which includes building in access for maintenance and realizing that biocontainment labs generally have high operating costs. He believed that the following advice and insights are useful for the construction phase: • Biocontainment labs are not the same as other complex industrial facilities, so contractors and subcontractors should have appropriate experience with biocontainment labs. • Local availability of specified parts will be limited, and decisions on using alternate parts or waiting for parts from overseas can be critical to success. The commissioning agent can provide critical input on decisions that may impact commissioning and certification. • A dedicated project oversight team should be on-site to ensure quality while helping to maintain cost and schedule. For the commissioning and certification stage, Colonel Lyons recommended scheduling sufficient time (12-18 months minimum) and realizing that the lab certification process in many countries is evolving. Planning a Cost-Effective and Sustainable BSL-3 Ken Ugwu (Global Partnership Program, Canada) described lessons learned during Canada’s recent efforts to engage with the Kyrgyz Republic. Mr. Ugwu opened by saying that as part of its $1 billion commitment to the Global Partnership Against the Spread of Weapons and Materials of Mass Destruction, which includes $100 million for biological non-proliferation, Canada wanted to undertake a large-impact project

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47 Paths from Assessments to Functional Labs in the former Soviet Union. Canada ultimately chose to assist the Kyrgyz Republic, which has endemic diseases of terrorist concern (e.g., plague, anthrax, and foot and mouth disease), a large number of substandard and insecure labs, and numerous poorly documented pathogen collections. Canada and the Kyrgyz Republic ultimately agreed to undertake a comprehensive assistance program including development of national biosafety guidelines, training, a twinning program with Canada’s Winnipeg lab, scientific engagement, help establishing the Biosafety Association for Central Asia and the Caucasus, interim security upgrades, and a new biological containment laboratory. Early on, the Canada/Kyrgyz Biological Laboratory Working Group (BLWG) was formed to oversee all phases of lab design, construction, and operation. The BLWG, which included participants from all Ministries, underwent an extensive education and training program on the complexities of BSL-3 labs, met every 6 weeks in the Kyrgyz Republic, and worked closely with architects and engineers. During the design process, the BLWG also formulated a sustainability and transition plan that made provisions for long-term financing. The BLWG worked with a community liaison group that included representatives from the Kyrgyz community at large, the city of Bishkek, the province of Chui, the Kyrgyz government, non-governmental organizations (NGOs), academics, and the health and agricultural communities. Additionally, an International Peer Review Group provided expert advice. Mr. Ugwu also described a number of steps the project took to combat the local scarcity of technical equipment and expertise in an effort to reduce costs and improve sustainability. As much as possible, the facility was planned in accordance with the capabilities of local trades and used local materials. To that end, the project team identified local factories that could manufacture needed equipment (e.g., high-efficiency particulate air [HEPA] boxes), and the architectural and mechanical team made many visits to investigate local capacities and materials. Mr. Ugwu also presented a number of decisions that were made to both control costs and improve the resulting facility: • To allow flexibility and the consideration of several BSL-3 design options, Canada chose to use WHO guidelines. • The BLWG worked to reduce uncertainty about the desired lab capabilities as uncertainty leads to overdesign and increased upfront and maintenance costs. • Most of the lab space was zoned for BSL-2 work, with BSL-3 space limited to essential functions; architectural and mechanical components of the BSL-2 and support spaces were not over-designed. • The BLWG targeted the most expensive components—mechanical and electrical—for savings. (Structural, architectural, and fixed equipment are comparatively inexpensive.) • Human and animal work was placed in the same building to allow the groups to both share common services and to collaborate. • Instead of building a large vivarium, animal rooms were integrated into the BSL-3 space. Animal containment was designed to use simple filter bonnet cages and flexible isolators instead of a ventilated rack system. While frequent cage changes would be required, the inexpensive labor in the region made the decision economical. • Workflow analysis was used to optimize the flow of people and wastes. Heating, ventilation, and air conditioning (HVAC) and effluent treatment facilities were placed to limit expensive ductwork and piping and to reduce the length of pipes to maintain. • After extensive discussion about ventilation, the BLWG chose a simple volumetric offset flow that creates a “leaky” BSL-3 over the more complex differential pressurization control, which produces an airtight facility. • Type IIB2 BSCs were limited in favor of type IIA2 BSCs.

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48 Biosecurity Challenges Mr. Ugwu concluded by noting that the project is on hold due to Kyrgyz Republic politics. Why We Need a BSL-3 Laboratory at the Pendik Veterinary Control and Research Institute Aysen Gargili (Marmara University, Turkey), delivering a presentation that was prepared in cooperation with Ayse Selma Iyisan (Pendik Veterinary Control and Research Institute, Turkey), described the changes that have taken place at Pendik Veterinary Control and Research Institute in Istanbul, Turkey from its founding in 1894 as a facility for the production of cattle plague serum to its present installation of a BSL-3 lab. Currently the Pendik Institute works under the Turkish Ministry of Agriculture and Rural Affairs (MARA) and has ties with the Food and Agriculture Organization of the United Nations (FAO), World Organisation for Animal Health (OIE), the European Union (EU), and the WHO Mediterranean Zoonoses Control Center. In addition to its research, diagnostics, education, publishing, and project development duties, Pendik Institute also serves as the national reference lab for sheep and goat pox, animal brucellosis, animal mycoplasmosis, anaerobic diseases, Theileria annulata, Marek’s diseases, and the detection of drug residues. Pendik Institute also produces 17 vaccines and 22 serums, antigens, and biological materials. As one of three institutes in Turkey with avian influenza (AI) virus identification capabilities and one of eight with the ability to isolate virus, Pendik Institute has played a major role in detecting and combating AI in Turkey. The first case of AI in Turkey was reported on 5 October 2005 and between 25 December 2005 and 26 February 2007, there were 247 confirmed cases in Turkey of which 246 were highly pathogenic avian influenza (HPAI) H5N1 virus and one of which was H7N1 virus. Overall, 217 outbreaks occurred in domestic poultry and 30 in wild birds. Both OIE and the EU were notified. Overall, Pendik Institute tested 2,278 samples for avian influenza and found 78 positive results. In response to the outbreaks, an EU-funded project implemented by Conseil Santé helped the Turkish MARA and Ministry of Health formulate a coordinated preparedness and response plan.2 The project’s overall objectives were to minimize the threat to humans in Turkey posed by HPAI infection in domestic poultry and other animals, to diminish the burden of disease and loss of productivity, and to improve influenza pandemic preparedness. Specific tasks included developing and improving the regulatory framework, upgrading surveillance programs, strengthening veterinary services, and raising public awareness about good poultry keeping practices and biosecurity measures. As the three labs responsible for virus identification and pathogenicity characterization under the plan (Pendik Institute and labs at Bornova and Etlik) did not meet the safety recommendations for the proposed work, the General Directorate of Protection and Control decided to upgrade them to BSL-3 capabilities using World Bank funds. Currently, the new BSL-3 lab at Pendik Institute is involved in the final stages of staff training and equipment installation. More information about the lab is available in Appendix D. The History and Current Status of the Chumakov Institute of Poliomyelitis and Viral Encephalitides Evgeniy Tkachenko (Chumakov Institute, Russia) described how the Chumakov Institute of Poliomyelitis and Viral Encephalitides has kept its focus aligned with the current public health threats to Russia. 2 Technical Assistance to Avian Influenza Preparedness and Response. Available at: http://www.kkgm.gov.tr/TR_06_AI_SV_new/English/start.htm. Accessed August 29, 2011.

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49 Paths from Assessments to Functional Labs Dr. Tkachenko explained that Chumakov Institute was founded in 1955 within the USSR Academy of Medical Sciences as a center for the study of poliomyelitis. The Institute subsequently produced both inactivated and oral poliomyelitis vaccine. Using oral poliomyelitis vaccine, the USSR started mass immunizations in 1959, and in 2002, WHO declared Russia free of poliomyelitis. Unfortunately, poliovirus has since been reintroduced to Russia, likely from Tajikistan. Chumakov Institute hosts the WHO Regional Reference Polio Laboratory for Russia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Tajikistan, Turkmenistan, Uzbekistan, and Ukraine. In addition to polio vaccine, Chumakov Institute has also produced vaccines against yellow fever, influenza A, hepatitis A, rabies, tick-born encephalitis, Crimean-Congo hemorrhagic fever (CCHF), and measles as well as cell culture media and hantavirus test- systems. As the diseases of epidemiological importance to Russia have changed, Chumakov Institute has modified its research agenda accordingly. For example, Russia now has approximately 3 million carriers of hepatitis B virus, which is currently one of the Institute’s areas of emphasis. The impacts of hemorrhagic fever with renal syndrome, CCHF, and West Nile virus on Russia have also increased recently and are now garnering more scientific attention. Dr. Tkachenko noted that Chumakov Institute has taken a number of steps to maintain and improve its facilities. For example, the Institute recently updated the inventories of its collections of nine virus families that range from hazard groups 2 through 4 in the Russian system. (In the Russian system, hazard group 1 organisms are the most dangerous and hazard group 4 are least dangerous.) Out-of-date infrastructure in the research complex was renovated and a lab for working with hazard group 2 organisms was created and registered according to Russian national safety requirements. The certification was expensive (500,000 rubles) and will soon need to be renewed. As a reminder of how dangerous the work can be, Dr. Tkachenko ended by showing a picture of six researchers, including himself, who had been infected with hantavirus or arenavirus during their research. SYNTHESIS OF BREAKOUT GROUP DISCUSSISONS Throughout the discussion, many participants remarked on the benefits of involving everyone including architects, designers, the lab director, scientists, contractors, certifiers, and the community from the very start and keeping them involved throughout the process. Additionally, individuals made comments on four main topics areas: Planning, Design, and Construction Many participants added to the recommendations offered during the presentations. In deciding whether or not a lab should have BSL-3 capabilities, one person argued that while a country may need to study endemic agents that routinely cause health problems, which typically requires BSL-3 facilities, it may be sufficient to simply diagnose imported diseases using molecular techniques in BSL-2 conditions. Others suggested expecting problems and budgeting for them, involving a workflow specialist, training local craftsmen, and identifying good contractors and project managers through a pre-qualification mechanism. Someone else warned that architectural and engineering consultants, who typically receive a percentage of a facility’s cost, have a strong incentive to overdesign, which can increase both upfront and maintenance costs.

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50 Biosecurity Challenges Maintenance Much of the discussion about maintenance highlighted the difficulties in finding funds and expertise. Several people observed that obtaining money for new labs was much easier than finding money for maintenance, as maintenance is often considered overhead and the return on specific expenditures is often difficult to quantify. One person advocated creating a facility’s maintenance plan as part of the design and construction process, and another observed that there was nothing worse than a good lab in bad condition. Many people expressed the opinion that ideally parts and qualified workers should be available locally but are often not. Several people noted that more countries are now producing their own HEPA filters and components and that many donors are training local technicians to service BSCs. One person indicated that it might be useful to have a group that certifies BSL-3 equipment in Africa, and others suggested requiring suppliers and manufacturers to train local maintenance and engineering personnel as part of their contract. Several people also commented on the often-ignored requirement to certify BSCs annually. One person wondered whether expensive, annual certification was really necessary and wondered if simple tests to detect reduced cabinet function could be devised. Another questioned whether workers, lab managers, or countries themselves should take responsibility for equipment, and asked if countries needed legislation to force annual certification. Certification Many felt that certification was desirable in theory but pointed to a number of practical problems. The largest difficulty reported was in finding qualified certifiers who were independent of those who built and maintain the lab. Several commented on the lack of competent local certifiers and the prohibitive expense in bringing in external certifiers. One person suggested that certification groups should contain multidisciplinary expertise. Another wondered if perhaps WHO or another organization could oversee the certification of these inspectors. A frequently expressed frustration was in determining which standards should be used during a certification. Some proposed certifying against a lab’s written SOPs, regardless of whether or not they conform to external standards. Others noted that for lack of better options, certification is often done against the WHO Laboratory Biosafety Manual (LBM) or BMBL guidelines. Training and Human Capacity Many people remarked that “laboratories” are not just buildings, but also the humans who work in them and that improving the practices of lab workers is often the easiest, most effective, and least expensive way to improve safety and security. Nonetheless, other individuals indicated that often skilled workers are not available, good training is frequently not offered, and that even among trained workers complacency can be a problem. Someone else suggested that “biosafety professional” is not perceived as an attractive career path. A number of people described difficulties in retaining qualified workers: • Experienced people may leave a developing country for higher paying jobs abroad. • Individuals may change jobs when a grant runs out. • New, well-equipped labs may drain qualified people away from labs in other parts of the country leaving pre-existing labs understaffed.

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51 Paths from Assessments to Functional Labs • Pregnant women may stop working in containment labs due to perceived risks (One participant supported this practice). Participants then offered a range of suggestions. One person suggested that initial training emphasize routine tasks, such as the proper use of personal protective equipment, and another suggested that some entity certify people as being qualified to work in BSL-3 labs. One argued that institutions, in spite of the expense involved, needed to be willing to fail people during internal training; another added that people who don’t follow rules should be removed. Someone else felt that new labs should be willing to train students rather than taking trained people from elsewhere.

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