E1. Overview of Biosafety and Biosecurity in High-containment Labs in Brazil: A Report of the Brazilian Biosafety Association

Leila dos Santos Macedo, Ph.D. Brazilian Biosafety Association

Background and Disclaimers:

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The Brazilian Biosafety Association (ANBio), whose main objective is to improve biosafety and biosecurity in Brazil, prepared this report in response to a 2 April 2009 letter from the United States National Academy’s Committee on International Security and Arms Control (CISAC). The Brazilian Government has no responsibility for this report or for the information in it.

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ANBio recognizes the importance of CISAC’s project on the risks and responsibilities associated with the international expansion of high-containment laboratory accidents, as well as the importance of following international guidance and agreements to reduce biological threats.

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This report was produced from survey data collected by ANBio as part of their capacity building program on biosecurity (Figure E1.1). The survey took place from May 2008 through February 2009. Overall, 237 questionnaires were received, which included responses from two institutions in other South American countries (Peru and Equator). The data presented reflects that submitted by survey responders; as such, ANBio is not responsible for any misleading or incomprehensive information.

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In producing this report, ANBio also considered presentations exhibited by representatives of the Brazilian Government during ANBio’s capacity building program.

Figure E1-1

The results of a survey conducted by ANBio about the state of biosafety and biosecurity in biological research institutions across Brazil (including two from Peru and Equator). The survey took place from May 2008 to February 2009, and 237 questionnaires were received.

SOURCE: Data are the result of a survey conducted by ANBio.

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What high-containment biological research facilities exist in your country?

In Brazil, only those laboratories conducting research related to public health, agriculture, and genetically modified organisms (GMOs) are subject to government regulation. There is no oversight or evaluative mechanism for laboratories, high-containment or otherwise, that are established at public or private universities for research activities with biological agents (other than GMOs). So, the answer here refers to public health, agriculture, and GMO laboratories only.

There are a total of 12 BSL-3 laboratories under the responsibility of the Ministry of Health and 8 BSL-3 laboratories under the responsibility of the Ministry of Agriculture (Table E1-1). Brazil currently has no BSL-4 laboratories, although there has been ongoing discussion about building one.

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What government organizations are responsible for safety and security of high-containment biological (high BSL) laboratories?

The Ministry of Health is responsible for public health laboratories; the Ministry of Agriculture is responsible for agriculture laboratories. For university labs (except GMO labs), there is no oversight body. For laboratories working with GMOs, the National Biosafety Committee (CTNBio) is the responsible organization.

In March 2008, the Brazilian Ministry of Science and Technology published a resolution with a list of selected agents. The definition of “selected agent” is the same used by the United States Centers for Disease Control and Prevention: “selected agents are those considered by the Health and Human Services to pose a severe threat to human and/or animal health.” With the exception of camel pox virus, Phoma glycinicola, and Rathayibacter toxicus, the Brazilian selected agent list includes all of the agents and toxins on the United States Health and Human Services and United States Department of Agriculture lists. The Brazilian list also includes additional microorganisms, toxins, and some equipment used in BSL-2 and BSL-3 laboratories (Table E1-2). Labs using select agents may voluntarily notify the government. Notification results in informal government visits and additional training.

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If there are BSL laboratories in your country, are there established criteria for deciding:

a.

Whether or not to establish such facilities?

The specific criteria are established by the corresponding Ministry as described in the previous answer. For universities, as referenced earlier, it is difficult to evaluate those criteria as they work independently except for laboratories working with GMOs.

b.

What criteria are used to select the placement of such facilities? What criteria are used to decide what research will be done in such facilities?

The following are considered: public priorities, prevalence of a specific biological agent, police priorities of the state, institutional support, and institutional capacity to maintain the project.

c.

What scientific, technical, and management advice is available to governments when making their decisions.

Each Ministry has advisory groups composed of specialists with a variety of expertise. Those specialists are scientists from the Ministries who can give advice to specific projects when required. Also, the Ministry of Health works closely with the World Health Organization (WHO), Pan-American Health Organization (PAHO) and the Centers for Disease Control (CDC) and can consult these organizations for specific projects when necessary.

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What standards exist for BSL laboratories?

a.

For engineering and construction? For licensing? For safety and security?

Different Ministries have produced some manuals and documentation. The biggest challenge, in our opinion, is to disseminate those materials broadly and make them available to all of the relevant institutions. Again, there is a gap in the case of universities (excluding GMOs labs) for which regulation does not exist. Furthermore, the focus is on biosafety. Biosecurity as a separate issue has only recently been addressed in Brazil.

b.

For regular oversight and re-certification?

There is almost no information on these issues and certification is pending for most of the BSL-3 labs within the country.

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Have there been any BSL accidents in your country?

Yes. Some are reported in master’s and doctoral theses and Brazilian journals, but there is no regular system for notification from which to produce a comprehensive report. Thus, the available data significantly underestimates the actual cases. For hospital workers, however, there is a formal system for accident notification. Thus, most published data on accidents are related to hospital professionals (mainly nurses). For health care workers, some studies have shown that most of the accidents are due to overwork, inadequate personnel protective devices, and working with sharp materials.

a.

If yes, how and why did accidents at high-containment facilities occur?

About 55 percent of the reports mention absent or non-fitted personnel protective equipment. Overwork was the second most common contributing factor.

b.

How, to whom, and when are they reported?

In some cases, accidents are reported to the Institutional Biosafety Committees or to the Commission on Prevention of Hospital Infections. There are no specific guidelines for labs not working with GMOs, and there is no regular and mandatory system for accident notification or for notification of liability measures. However, some voluntary guidance is available (Ministry of Health publication in 2010).

c.

Who has authority to investigate accidents?

For GMO work, authority rests in the Institutional Biosafety Committee and/or CTNBio (Law 11.105/2005). For other types of work with biological agents, there are no provisions.

d.

What disciplinary or legal actions can be taken?

There are only provisions for working with GMOs.

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Have any steps been taken to minimize BSL laboratory accidents?

Since its foundation in 1999, ANBio, a non-profit society, has dedicated the bulk of its work to training researchers and biological science students on biosafety measures and procedures.

As part of ANBio’s effort, the Brazilian Government has taken a step forward in establishing a biosafety program at public health laboratories and added biosafety university courses to the graduate and post-graduate curriculum. The courses concentrate on biosafety for GMOs but discuss biosafety generally and last between 40 and 420 hours. The courses are multidisciplinary and have attracted pharmacy, biology, medicine, veterinary science, chemistry, agronomy, and engineering students. The courses include the following topics:

• A review of microbiology, biochemistry, immunology, and plant physiology
• Risk classification, assessment, and management
• Personal protective clothing and equipment
• Biosafety regulations
• Biosafety of GMOs
• Animal biosafety
• Waste treatment and transport
• Bioethics, intellectual property rights, and biosecurity
• Design of facilities and commissioning
• Case studies

Most recently, the Brazilian Ministry of Education (Coordination of Post-Graduation Courses-CAPES), the U.S Biosecurity Engagement Program, and the Oswaldo Cruz Foundation (Fiocruz) supported ANBio’s development of a new post-graduation course on biosafety and biosecurity (specialization with a total of 180 hours). Forty students took the course the first time it was offered.

Additionally, in 1999, the Ministry of Health started a project to enhance the capacities of BSL-3 public health laboratories. Since then, 12 facilities have been reviewed and more than 4,000 professionals have been trained. In our opinion, however, an important challenge is the lack of regular equipment maintenance and facility certification. Also, training should be regular and frequent. In particular, regular training should be included in the biosafety program of all laboratories working with selected agents.

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Have any steps been taken to increase security at BSL facilities?

In 2004, Brazil established the National Program for Sensible Goods (PRONABENS) in order to meet Resolution 1540/2004 of the UN Security Council. Since then, the PRONABENS team has conducted site visits, which included presenting talks on biosecurity. ANBio has worked together with this team, and they have participated in ANBio’s capacity-building program on biosecurity since 2007.

In 2007, ANBio, with the support of the United States Biosecurity Engagement Program, offered Brazil’s first biosecurity course.

Currently, ANBio is organizing our VII Brazilian Biosafety Congress and a “Biosafety and Biosecurity Conference for Latin America and the Caribbean” to be held from September 19-23, 2011 in Joinville, Brazil.

Additionally, ANBio is starting to plan and seek support for a project on “Virtual and in situ training on procedures for detection and control of biological threats” in order to support the 2014 World Cup and the 2016 International Olympiad, both which will be held in Brazil.

Even in light of these actions, Brazil should still create a long-term biosafety and biosecurity program with a dedicated budget, in which all stakeholders should take part. The main gaps that should be addressed are maintenance, certification, waste management, and the lack of a global inventory of samples. Brazil also needs to decide how and whether to destroy its polio samples post-eradication.

E2. HIGH-CONTAINMENT MICROBIOLOGY LABORATORIES IN EUROPE

Ingegerd Kallings,^a M.D. and Kathrin Summermatter,^b Ph.D. ^aSwedish Institute for Communicable Disease Control, Stockholm, Sweden ^bInstitute for Virology and Immunoprophylaxis, Mittelhaeusern, Switzerland

This report is partly based on the final report from the Consortium project BIOSAFETY-EUROPE, funded by the 6th Framework Program of the European Commission: Co-ordination, harmonization and exchange of biosafety and biosecurity practices within a pan-European network.¹

BIOSAFETY-EUROPE, a coordination action within the European Commission 6th Framework, had the aims to explore harmonization and exchange of biosafety and biosecurity practices within a pan-European network. The consortium included expertise in biosafety, biosecurity, risk assessment and control, containment measures, and on the underlying legal frameworks of the European Union and its Member States (MS). The consortium was comprised of 18 partners from 10 European countries representing industry, academia, and government agencies. It commenced in April 2006 and lasted until the end of 2008. Through detailed questionnaires, information was gathered on the implementation of European biosafety legislation on the national level and on physical containment, practices, and procedures at containment levels 3 and 4. Laboratory biosecurity was addressed as well.

High-containment biological facilities in Europe

A first questionnaire (Q1) was sent to 319 containment level (CL) 3 and 4 laboratories in the 27 EU MS identified through national regulatory agencies and through personal knowledge by consortium partners (see Figure E2-1). Responses were received from 98 laboratories (13 CL 4; 85 CL 3) in 18 countries. Questions were asked on lab type (government, private, academia, or industry), lab activities (clinical, public health, research, human and/or animal, food, defense), the national regulatory framework and the implementation of EU legislation, the implementation of biosafety and biosecurity management and associated controls, and inspection regimes.

EU and national governance of high-containment biological facilities

At the highest EU level, many departments (DGs) deal with laboratory biosafety and biosecurity e.g., DG Health and Consumers, DG Research and Innovation, DG Home Affairs, DG Environment, DG Mobility and Transport, DG Employment, and Social Affairs and Inclusion. More directly, safety at work with biological agents is the responsibility of the EU Occupational Health and Safety Agency (EU-OSHA) that developed the EU Directive 2000/54/EC on the protection of workers from risks related to exposure to biological agents at work.²

EU MS are obliged to implement EU Directives, and all 27 MS have reported to the EU they have adopted and implemented Directive 2000/54/EC. MS must not delete any requirements from EU legislation when adopting it into national legislation, but some countries have additional requirements.

Figure E2-1

Country distribution of CL3 and CL4 laboratories that received the first questionnaire (Q1). The CL3 labs follow a variety of different standards. Additionally, the term “CL4” is not used consistently throughout Europe. CL4 labs may be glove box labs or suit labs. In some countries, a lab (e.g., a veterinary lab) that works with foot and mouth disease virus is automatically considered CL4. The numbers reflect all laboratories to which the questionnaire was sent, including some that were in the planning phase at the time.

SOURCE: BIOSAFETY-EUROPE

NL: Netherlands; CZ: Czech Republic; UK: United Kingdom; CH: Switzerland; HU: Hungary; DE: Germany; SE: Sweden; FI: Finland; FR: France; BE: Belgium; IT: Italy; NO: Norway; DK: Denmark; IR: Ireland; CY: Cyprus; GR: Greece; LV: Latvia; PL: Poland; PT: Portugal; SI: Slovenia

In many countries, several ministries, agencies, and organizations are involved in oversight of biosafety and the regulatory framework for biosafety (e.g., Ministry of Health, Ministry of Agriculture, Ministry of Environment, Ministry of Internal Affairs/Occupational Health) whereas the Ministry of Defense and the Ministry of Foreign Affairs usually are involved in biosecurity in a wider sense. In some countries, there is a department within the Ministry of Health (occasionally the Ministry of Defense) whereas other countries have an independent government agency as the main authority for biosafety matters as in Sweden where this responsibility lies with the Swedish Work Environment Agency. It was clearly shown by the BIOSAFETY-EUROPE findings that the interpretation and implementation at the actual laboratory level of the common EU legislation varied greatly between MS.

A recent inventory made by the European Biosafety Association (EBSA) found that 20 of 27 countries have a body (agency, commission, or committee) regulating or providing advice on the contained use of Genetically Modified Microorganisms (GMM). For the remaining seven countries, no information was available.

In addition, there are a number of agencies at the EU level dealing with the implementation of biosafety and biosecurity regulations and guidelines: the European Agency for Safety and Health at Work (EU-OHSA), the European Centre for Disease Control and Prevention (ECDC), the European Food Safety Authority (EFSA), the European Food Information Council (EUFIC), the European Commission’s Joint Research Centre (JRC), the European Medicines Agency/European Agency for the Evaluation of Medicinal Products (EMEA), and the European Molecular Biology Laboratory (EMBL). Several nongovernmental organizations are involved: the European Federation of Biotechnology (EFB); the Federation of European Microbiological Societies (FEMS); the Confederation of the Food and Drink Industries of the EU (CIIA); the International Centre for Genetic Engineering and Biotechnology (ICGEB); the European Association for Bio industries (EuropaBio); EU News, Policy Positions & EU Actors online (EurActiv.com); and the European Society of Gene Therapy (ESGT).

Internationally, the World Health Organisation (WHO), the World Organisation for Animal Health (OIE), and the Food and Agriculture Organisation (FAO) issue guidelines in biosafety and biosecurity. These guidelines have recommendatory character, but they often influence the development of EU-wide and national regulatory frameworks.

BIOSAFETY-EUROPE - Biosafety Findings

National biosafety regulations and practices derived from EU Directives 2000/54/EC¹ and 98/81/EC² varied from country to country. In many countries, the regulatory framework for genetically modified microorganisms (GMMs) was more strongly enforced than that for biological agents in general. There is often no specific biosafety regulation for epizootics except for those microorganisms regulated under the two guidelines mentioned above.

Facilities and practices in containment level 3 laboratories throughout the EU are not of a comparable standard, e.g. a large range of different terminologies for “containment level (CL)” were used within the MS. Many laboratories referred to the WHO term ‘biosafety level (BSL). It was concluded that EU Directives 2000/54/EC³ and 98/81/EC require revision and updating to reflect the current state-of-the-art including continuous review of the classification list of microorganisms and the definition of harmonized best practices. (The Directive 98/81/EC has since been revised and replaced by 2009/41/EC,⁴ but many inconsistencies remain).

Moreover, biosafety responsibilities appear often to be attributed to staff in management positions with functional roles that could be in conflict with strict biosafety considerations. Less than half of the respondents were subject to oversight by a biosafety committee.

EC legislation on biological agents and GMMs is often not specific enough to ensure harmonization of the implementation on the national level. There is a lack of European-wide harmonized practical guidance on how to implement the European Directives on biological agents and GMMs. A few EU Member States have developed their own national guidance based on the EC Directives. In other cases, these gaps are filled by e.g., U.S. Biosafety in Microbiological and Biomedical Laboratories (BMBL) and Canadian guidelines. The varying interpretation of the EU Directives allows different approaches to biosafety and laboratory biosecurity. This and differences in terminology make the exchange of scientists between member states problematic.

BIOSAFETY-EUROPE - Biosecurity Findings

Laboratory biosecurity is a relatively new concept that is still developing, and during the project period there was little consensus across Europe as to what biosecurity means, even within the laboratory environment. BIOSAFETY-EUROPE used the term “Laboratory Biosecurity” to describe protection against, control of, and accountability for biological agents and toxins within laboratories, in order to prevent their loss, theft, misuse, diversion, unauthorized access, or intentional unauthorized release (adapted from WHO⁵).

In contrast to this more laboratory-focused definition, it has to be mentioned that the term “livestock biosecurity” has long existed in the veterinary field and describes the prevention of disease-causing agents entering or leaving any place where farm animals are present.

No EU level legislation exists that has been specifically developed to address the protection of biological agents in the laboratory from loss or willful misuse. However, due to the many synergies between biosafety and biosecurity, the EU Directives developed to protect workers from exposure to biological agents or GMMs address most of the issues related to laboratory biosecurity. Only a few Member States are known to have introduced special laboratory biosecurity legislation i.e. England and Denmark. Many facilities implement some biosecurity controls, but these are often focused on physical security and often are not based on a specific risk assessment. Less attention is paid to information security or organizational security issues, despite the fact that internal threats from individuals with authorized access to the laboratory must be recognized.

The recently adopted Minimum standards for laboratories working with FMDV in vitro/in vivo (Council Directive 2003/85/EC⁶) is the only binding European document including some aspects of biosecurity. The implementation of this standard is mandatory for laboratories handling live foot and mouth disease virus (FMDV).

Criteria for establishing containment facilities

There are currently no common criteria on the European level for the establishment of containment facilities with regard to rationale, work to be performed, and placement of the facility. However, the EU Directive 2000/54/EC⁷ classifies microorganisms into 4 risk groups, based on the WHO criteria, and states that the application of Directive requirements will follow a risk assessment. Some countries may have national regulations, rules, or guidelines.

As indicated above, the differences between MS are huge in biosafety and laboratory biosecurity regulatory framework implementation. Most countries have a National Board of Health, a Central Public Health Institute, and a National Veterinary Institute providing expert advice on the handling of biological agents and toxins.

Standards

There are several ISO/EN standards available in the EU that can be applied for containment laboratory planning, construction, and operation e.g., ISO/EN 15189:2003 Medical laboratories—Particular requirements for quality and competence, CEN/CR 12739:1998 Biotechnology—Laboratories for research, development and analysis—Report on the selection of equipment needed for biotechnology laboratories according to the degree of hazard. In addition there are CEN standards developed for biosafety equipment e.g., autoclaves, biosafety cabinets, and personal protective equipment. National standards may cover the construction and the licensing of containment facilities, but there is no harmonization of licensing across Europe. Regular oversight and re-certification mainly depends on national specifications. Member States have a national standardization institute making CEN standards available in the country.

Laboratory-associated Infections (LAI)

No harmonized system for the reporting of laboratory incidents and accidents is in place in the EU. Few laboratory-associated infections (LAI) and laboratory incidents/accidents have been reported in the literature from Europe during the recent decade (see Box E2-1). There is reason to believe that a serious underreporting is at hand. National reporting systems are not easily accessible. Historically, Northern European countries report higher numbers of LAI than other parts of Europe, presumably reflecting failure to recognize LAI as such as well as reporting inefficiencies. There is a variation between MS regarding to whom and when to report, who investigates the incident, and if there is a possibility for legal actions. Many MS are taking steps to improve the status of biosafety in their laboratories, and awareness of biosecurity issues is increasing.

Box E2-1

During 2000-2010, only 5 incidents of release and/or exposure to infectious agents in risk class 3-4 were reported in the literature from EU Member States: In 2000, a broken centrifuge tube caused 12 cases of brucellosis in Italy;

Future outlook - EU CBRN Action Plan

On June 24, 2009, the European Commission adopted its communication on strengthening chemical, biological, radiological, and nuclear (CBRN) security in the European Union—as an EU CBRN Action Plan.⁸ The overall goal is an all-hazard approach to reduce the threat of and damage from CBRN incidents of accidental, natural, or intentional origin, including acts of terrorism. The Action Plan has set up a number of goals within three areas: prevention, detection, and preparedness and response:

Prevention

• Develop EU lists of high risk CBRN materials and risk-based approaches to security;
• Enhance the security of high risk CBRN facilities;
• Enhance control over high risk CBRN materials;
• Contribute to the development of a high security culture among staff;
• Improve the identification and reporting of suspicious transactions and behavior;
• Enhance the security of transport;
• Improve information exchange;
• Strengthen the import/export regime; and
• Strengthen cooperation on the security of nuclear materials.

Detection

• Establish a scenario-based modeling approach to identifying work priorities in the detection field;
• Establish trialing, testing, and certification schemes for CBRN detection in the EU;
• Develop minimum detection standards;
• Identify good practices related to the detection of CBRN materials, awareness-raising, and training; and
• Improve the exchange of information.

Preparedness and response

• Improve emergency planning;
• Strengthen countermeasure capacity;
• Improve domestic and international information flows regarding CBRN emergencies;
• Develop improved modeling tools and strengthen decontamination and remediation capacity; and
• Improve the capacity to conduct criminal investigations.

Actions encompassing all CBRN fields are listed as 67 horizontal actions whereas there are 14 B-specific actions listed, among them:

• To assist the MS in the proper implementation of applicable procedures at “the laboratory bench level” and in developing mechanisms for assessing and monitoring its correct implementation;
• The MS should establish:
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    a registry of facilities possessing any of the substances on the EU list of high risk biological agents and toxins;
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    a process to verify whether security arrangements of facilities are adequate, including diagnostic laboratories handling and possessing any of the EU list of high risk biological agents and toxins;
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    a mechanism within facilities storing biological agents and toxins on the EU list of high risk biological agents and toxins to regularly review the need for such biological agents and toxins;
• The Commission together with the MS should take relevant steps so that:
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    a comprehensive overview of the relevant regulations or standards at hand and their relevance to biosecurity and biosafety is achieved;
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    facilities possessing substances on the EU list of high risk biological agents and toxins consider as appropriate the implementation of the CEN Workshop Agreement (CWA 15793⁹), WHO Laboratory Biosecurity Guidance, or their national equivalent standards -unless equal or more stringent national regulations have to be considered;
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    appropriate national regulations or standards are met as part of a national authorization or accreditation process or as a condition for issuing licenses for work with substances on the EU list of high risk biological agents and toxins.
• The Commission together with the MS should encourage professional and other relevant associations working on bio-issues to develop and adopt codes of conduct for their members;
• The Member States together with the Commission should define requirements for biosafety officers (roles, competences, and training).

Other areas addressed in the B-specific list of actions are: transport, detection, and validation of methods, establishment of reference material for quality assurance, international cooperation and networking, research, implementation of good practices, and improved cooperation between relevant agencies in crisis situations.

It is the responsibility of each Member State to protect its population against CBRN incidents and to implement the action plan, whereas the European Union can provide added value and support projects across the EU, to ensure a coherent and consistent approach to cooperation on this issue between the Member States.

The implementation of the EU CBRN Action Plan is now in its second year. Meetings with MS experts are frequently arranged by the Department of Home Affairs (former JLS).

E3. BIOTECHNOLOGY AND BIOSECURITY INITIATIVES IN PAKISTAN: A COUNTRY REPORT

Anwar Nasim,¹ Ph.D. and Erum Khan,² MBBS, FCPS, M. Sc. ¹Ministerial Standing Committee on Scientific and Technological Cooperation ²Pakistan Biological Safety Association and Aga Khan University Hospital

What high-containment biological research facilities exist in your country? What are the facilities’ main goals and priorities?

In Pakistan, many institutes work using BSL-1 and BSL-2 level facilities. The National Institute of Health, Islamabad has been working at BSL-2+ and is constructing BSL-3 facilities. BSL-3 facilities exist at Aga Khan University and Indus Hospital Karachi.

Priorities and goals vary among facilities. The National Institute of Health, for example, fulfils the 22 objectives defined in ordinance No. XLIII of 1980 including advising the Federal Government on disease control, investigating epidemics, developing an Institute of Tropical Diseases for Research and Training, developing a National Virus Reference Center, and functioning as a National Type Culture Collection Centre (http://www.nih.org.pk/). The BSL-2 and BSL-3 laboratories at Aga Khan University are private diagnostic laboratories that process routine clinical samples. The BSL-3 laboratory is primarily used for processing samples from patients suspected of Mycobacterum tuberculosis (TB) infection. The BSL-3 lab at Indus Hospital is used mainly for TB diagnosis.

What government organizations are responsible for safety and security of high-containment biological (high BSL) laboratories?

Responsible organizations include the Disarmament Division, the Ministry of Foreign Affairs, and the National Biosafety Committee. Additionally, the Pakistan Biosafety Rules 2005 require organizations involved in biotechnology or genetic manipulation to have Institutional Biosafety Committees and to designate a Biosafety Officer.

If there are BSL laboratories in your country, are there established criteria for deciding:

a.

Whether or not to establish such facilities?

b.

What criteria are used to select the placement of such facilities?

c.

What criteria are used to decide what research will be conducted in such facilities?

d.

What scientific, technical and management advice is available to governments when making their decisions?

The Pakistan Biosafety Rules, 2005, which concerns genetically modified organisms, established the following entities:

• The National Biosafety Committee whose responsibilities (related to genetically modified organisms) include establishing procedures and standards for risk-assessments, facilitating the exchange of technical advice, developing guidelines for assessing biohazards, informing individuals engaged in genetic manipulations about new biosafety guidelines, coordinating efforts to prepare for biological emergencies, and certifying and inspecting laboratories that intend to perform high-risk work.
• The Technical Advisory Committee that examines applications and provides advice concerning work on and the release of genetically modified organisms.
• Institutional Biosafety Committees

Criteria used to decide what research will be conducted vary between facilities. Research at the National Institute of Health, for example, fulfils the 22 objectives defined in ordinance No. XLIII of 1980.

1.

What standards exist for BSL laboratories?

No standard formulations have been devised or received from the Government of Pakistan. The National Institute of Health, Islamabad, for example, follows the criteria and standard guidelines devised by WHO, the United States CDC’s Biosafety in Microbiological and Biomedical Laboratories (BMBL), and ABSA-Canada (Canadian Association for Biological Safety).

Additionally, in May 2005, The Pakistan Environmental Protection Agency issued National Biosafety Guidelines. The document provides guidelines on laboratory research, field trials, and release of genetically modified organisms.

2.

Have there been any BSL accidents in your country?

a.

If yes, how and why did accidents at high-containment facilities occur?

b.

How, to whom and when are they reported?

c.

Who has authority to investigate accidents?

d.

What disciplinary or legal actions can be taken?

According to the Pakistan Biosafety Rules, 2005, the Technical Advisory Committee must be notified following any accident that could lead to the release of genetically modified organisms.

3.

Have any steps been taken to minimize BSL laboratories accidents? If so, by whom (i.e., regulation, voluntary measures, individual laboratory practices)?

In his December 6, 2010 address to the BWC Meeting of the States Parties, Ambassador Zamir Akram stated that, “The subject of Biosafety has been incorporated in the curricula of relevant university disciplines.”

The Pakistan Biosafety Rules 2005 require an organization involved in bio-technology or genetic manipulation to designate a Biosafety Officer.

Pakistan currently has three Biosafety organizations including the Pakistan Biological Safety Association (PBSA), which is affiliated with the National Core Group in Life Sciences (NCGLS) of the Higher Education Commission and the Organization of the Islamic Conference (OIC) Committee on Scientific and Technological Cooperation (COMSTECH) and was started in 2008.

Additionally, a number of training activities and seminars on biosafety have taken place in Pakistan, and Pakistanis have participated in similar events abroad. For example, in 2009, Aga Khan University in Karachi held two seminars on Laboratory Biosafety and a National Training Seminar on Biosafety and Biosecurity Initiatives took place in 2007 in Islamabad. Similarly, Pakistanis attended the Asia Conference on Laboratory Biosafety and Biosecurity (Bangkok, Thailand, 2007); the Biosafety and Biosecurity International Conference: Healthier and More Secure Communities in the Middle East and North Africa Region (Casablanca, Morocco, 2009); the Biosafety and Biosecurity Risk Assessment and Risk Mitigation Training Event for Pakistani Bio-scientists (Dubai, United Arab Emirates, 2010); and the ICLS-COMSTECH-PAS International Conference on Conduct of Responsible Science: Safety, Security and Ethics (Islamabad, Pakistan, 2010).

4.

Have any steps been taken to increase security at BSL facilities? If so, by whom (i.e., regulation, voluntary measures, individual laboratory practices)?

In 2010, the Government of Pakistan’s Planning Commission issued a report on Biosafety and Biosecurity in Biological Laboratories that describes good microbiological practices and suggests that one lab in each province be brought into full compliance with BSL-2 practices and then used as a model.

In his December 6, 2010 address to the BWC Meeting of the States Parties, Ambassador Zamir Akram stated that, “the Inter-Agency Task Force on BWC issues has finalized ‘Guidelines for development of Code of Conduct for the Life Scientists’ and circulated them to all our national stakeholders.” Additionally, the documents were translated into the national language, Urdu.

E4. OVERVIEW OF HIGH-CONTAINMENT BIOLOGICAL LABORATORIES IN RUSSIA

Michael V. Ugrumov¹ and Sergey V. Netesov^{2 1}Councilor of the President of RAS on Foreign Affairs and Biology, Moscow, Russia ² Vice Rector, Research, Novosibirsk State University, Novosibirsk, Russia

Russia’s extensive experience in working with dangerous pathogens in high-containment laboratories can be traced back to the country’s early efforts to improve public health through research, vaccine production, and development and implementation of vaccination strategy.¹ The work led to success in antiplague efforts during the 1920s and 1930s, national eradication of smallpox in 1939, and the successful start of measles and poliomyelitis control through vaccine development followed by mass long-term vaccinations. That expertise has continued to the present day where the Russian Federation is home to 19 World Health Organization (WHO) Collaborating Centers including the WHO Collaborating Centre for Tuberculosis at the Central Tuberculosis Research Institute (CTRI), Russian Academy of Medical Sciences; the WHO Collaborating Centre for Orthopoxvirus Diagnosis and Repository for Variola Virus Strains and DNA at the State Research Center of Virology and Biotechnology (“Vector” Center) in Koltsovo (Novosibirsk Region), under Rospotrebnadzor supervision; and the WHO Collaborating Centre for Training in Multidrug-Resistant Tuberculosis at the Novosibirsk TB Research Institute.² The Vector Center also hosts a WHO Influenza H5 Avian Influenza Reference Center,³ and the WHO National Influenza Center is functioning actively in the St. Petersburg Institute of Influenza, which since last year has been supervised by the Ministry of Public Health and Social Development of the Russian Federation.⁴ Additionally, the Russian Federation also has two World Organization for Animal Health (OIE) Collaborating Centers⁵ and three OIE Reference Laboratories, which are responsible for dourine, equine rhinopneumonitis, and foot and mouth disease.⁶

The current practice of monitoring, studying, and controlling infectious diseases outbreaks in Russia is based on the following regulatory documents:

• Charter of Federal Service on Customers’ Rights Protection and Human Well-being Surveillance (Rospotrebnadzor) approved on 30.06.2004,⁷
• the 2005 International Health Regulations,⁸ and
• the State Order #60 dated 2 February, 2006.⁹

Building on these primary regulating documents, the special Order of Rospotrebnadzor #88 dated 17 March 2008 issued instructions about the measures on monitoring for infectious and parasitary diseases agents.¹⁰ This last order lists four types of research and monitoring centers:

1.

The list of regional centers for monitoring the infectious and parasitic disease agents of pathogenicity groups 2-4 (roughly equivalent to BSL1-3 according to WHO classification)—Appendix 1 in;¹¹

2.

The list of regional centers for monitoring the infectious and parasitic disease agents of pathogenicity groups 1-2 (roughly BSL-3-4 according to WHO classification)—Appendix 2 in;¹²

3.

The list of reference centers for monitoring the infectious and parasitic disease agents with functions under the International Health Regulations (20050—Appendix 3 in;¹³

4.

The list of national centers for verification of diagnostic work and national centers that fulfill the functions of State Collections of Rospotrebnadzor—Appendix 4 in.¹⁴

All Russian BSL-3 and BSL-4 laboratories are listed in these Appendices, including Russia’s 17 regional anti-plague centers. Additionally, this Order also describes the area of responsibility of each Institute/Center and charters types of these Institutes/Centers. The special national Sanitary Regulations (SR) one of which is the SP 1.3.1285-03 on “Safe handling of micro-organisms in pathogenic hazard groups I-II”,¹⁵ whose observance is mandatory, form the foundations of Russian laboratory practices for these Institutes/Centers as well as public health and educational university laboratories.¹⁶ The SR specify a full spectrum of biosafety practices including disinfection procedures, sewage water testing, safe transport of pathogens, and safe practices for hospital work. The SR also describe procedures for obtaining permission to work with recombinant DNA and Hazard Groups I-IV microorganisms from the State Sanitary-Epidemiological Inspection Committee¹⁷ and make provisions for laboratory inspections and compliance monitoring.¹⁸ Hazard groups I, II, II, and IV in the Russian classification system are roughly equivalent to the WHO’s risk groups IV, III, II, and I, respectively.¹⁹

Russia has stringent standards to prevent accidents at high-containment facilities, and the Sanitary and Epidemiological Regulations SP 1.3.1285-03 on “Safe handling of micro-organisms in pathogenic hazard groups I-II” describe the procedures to follow in response.²⁰ It is a result of a long history of work with dangerous pathogens in Russian microbiological laboratories during which time laboratory accidents took place a few times; some important laboratory infection cases that occurred in Russia between 1950 and 1990 are described in the paper of S. Gaidamovich et al.¹ As the result of this experience, during the recent two decades, in the rare cases when an accident occurred, treatment began immediately and the incident was thoroughly investigated. For example, in May 2004, an experienced technician who worked at the Vector Center pricked herself with a syringe needle containing blood from a guinea pig infected with Ebola virus. In spite of extensive prophylaxis and treatment she died. A commission including experts from two governmental agencies, the Russian Federal Service for Surveillance in the Sphere of Consumer Rights Protection and Human Well-being (Rospotrebnadzor) and the Federal Medical and Biological Agency (FMBA), subsequently conducted an investigation that revealed multiple violations of laboratory regulations by this experienced technician.² The additional lesson learned from this case was the need for more thorough training courses for experienced workers to prevent complacency.

Several Russian Universities, in collaboration with Health Canada and the Canadian Science Centre for Human and Animal Health, recently updated their biosafety curriculum.³ For example:

• The Saratov Anti-Plague Institute developed 13 new advanced training programs including a specialized primary training program in biosafety, a program for training specialized anti-epidemic teams to work in emergency situations, and a program for training bacteriologists and epidemiologists in the field of bioterrorism counteraction.
• A Train the Trainers Biosafety/Biosecurity Program organized with assistance of Canadian biosafety experts from Health Canada took place November 17-19, 2008 at the Moscow Medical Academy. As a result, the Moscow Medical Academy added a biosafety component to their advanced virology course.
• The Vector Institute re-established an advanced course for medical, biological, chemical (biotechnology), and veterinarian specialists. The 540-hour course focuses on virology, but also provides a basic microbiological background. The current course includes an expanded biosafety component as well as educational materials from the WHO and examples of biosafety regulations from other countries including the United States and Canada. In the experimental portion of the class, students work with vaccine strains using real laboratory equipment, real BSL-3 facilities, and real personal protective equipment.
• A few universities in Russia including M. V. Lomonosov Moscow State University and Novosibirsk State University (NSU) decided to include biosafety, biosecurity, and bioethics courses in their Master of Biotechnology educational programs. Recently, ISTC project #4060 (Establishment of a Center for personnel training in principles of biosafety in work with viral agents, on the basis of international recommendations and national biosafety requirements and guidelines) started at the NSU with the help of Health Canada specialists to assist Russian specialists to make this Center the most modern in Russia.

Specialists from M. V. Lomonosov Moscow State University, NSU, and a few other Moscow research institutes have also suggested modernizing the Russian educational standard in biotechnology during 2011-2012.

To facilitate biosafety education, the first Russian Glossary of Biosafety Terms was published in 2007; another variant of the Glossary was issued later in the same year. Finally, the first English-Russian Harmonized Dictionary in Biosafety and Biosecurity was published in November 2010.

Furthermore, Russia played a major role in sponsoring and preparing United Nations Security Council Resolution 1540, which requires all countries to take the necessary steps to prevent the proliferation of weapons of mass destruction,⁴ and hence Russia takes its biosecurity responsibilities very seriously. As a result, all, “biological materials are securely protected using modern technology, and the necessary counter-terrorist measures are taken.”⁵ Furthermore, the national legal framework details procedures to account for the production, use, storage, and transport of biological weapons and related materials and specifies how violators can be penalized.⁶ Additionally, microbiological and virological research facilities in Golitsino, Pokrov, Vladimir, Koltsovo (Vector Center), Obolensk, and Kazan recently upgraded their security through their participation in the United States Biological Threats Reduction program,⁷ and in collaboration with the International Science and Technology Center (ISTC), seven institutes invested over $18 million in upgraded operating procedures and physical security.⁸ During the last three years, two institutes—Vector Center and the Microbiolgical Center in Obolensk —additionally upgraded their biosecurity equipment and services.

The Russian Federation will undoubtedly continue its efforts to modernize its microbiological laboratories and biotechnological facilities in accordance with international standards and new achievements in biosafety and biosecurity will follow.

CONCLUSIONS:

1.

Periodical biosafety and biosecurity upgrades in laboratories working with dangerous pathogens are needed to better protect the environment, personnel, and to prevent possible terrorism cases.

2.

The modernization of educational courses in all areas of biotechnology and medicine should include basic educational modules on biosafety, biosecurity, and bioethics.

3.

The easiest and fastest way to upgrade the national level of biosafety/biosecurity is to study the modern international recommendations and textbooks in this area, to upgrade national biosafety regulations and standards, to modify the national educational programs, and to participate actively in international biosafety meetings and associations.

E5. HIGH-CONTAINMENT LABORATORIES – SWEDEN CASE STUDY

Ingegerd Kallings, Swedish Institute for Communicable Disease Control SE-171 82 Solna, Sweden

High-containment biological facilities in Sweden

Work with risk class 3 or 4 biological agents requires a permit from the competent authority, which reviews and evaluates that the containment measures chosen are adequate. Thus, one way to address the question of the number of containment laboratories is to look at the number of applications for such a work permit. There are currently 32 employers in Sweden with (one or more) permits to work in 40 sites with (one or more) risk class 3 biological agents. The risk classification in EU Directive 2000/54/EC applies. Most of these permits are for clinical diagnostic work with biological agents that are not airborne e.g., HIV, EHEC, and other gastrointestinal biological agents and thus requirements are less than for a complete containment level (CL) 3 laboratory. One permit is for storage of biological agents in a culture collection. Eleven employers have a permit to work in full CL 3 at 11 sites e.g., clinical mycobacterial laboratories. One employer may have one or more permits for work in one or more laboratories at different sites. There is one containment level 4 facility in Sweden.

National governance of high-containment biological laboratories

Government agencies in Sweden subordinate to a Government Department (Ministry) are responsible for implementing public policies, overseeing the provision of public services, and executing a range of regulatory functions. The Government decides on the preconditions for agencies’ operations through appropriation directions and ordinances.

The Swedish Work Environment Authority (SWEA)¹ is an independent government agency authorized by the Labour Ministry. With regard to biosafety, SWEA is responsible for the implementation of the EU Directive 2000/54/EC on the protection of workers from risks related to exposure to biological agents at work² and EU Directive 2009/41/EC on the contained use of genetically modified micro-organisms (GMM).³ EU Directives contain minimum requirements and Member States may add national requirements. Sweden has done so. EU Directive 2000/54/EC is implemented through national provisions: AFS 2005:01 Microbiological Work Environment Risks—Infection, Toxigenic Effect, Hypersensitivity.⁴ Regarding GMM, the SWEA provisions AFS 2000:05 Contained Use of Genetically Modified Micro-organisms⁵ following the previous EU Directive 98/86/EC are still in use but will be reviewed and updated to reflect changes in the most recent EU Directive 2009/41/EC⁶ on GMM. The regulatory text of the SWEA statute books is complemented by extensive recommendations on how to interpret and implement the law. A statute book on blood-borne infections will be updated shortly to follow the recent EU Directive,⁷ which will also be reflected in the AFS ordinance regulating biosafety.

Criteria for establishing containment facilities

There are no national criteria for the establishment of containment facilities in Sweden, neither for justification of the work nor for selection of sites. The respective management/owner of a facility in any sector (government/university/county level public health /private industry) decides what they intend to do and makes a proposal to SWEA for a work permit. SWEA does not question the rationale for the intended work; they check that safety criteria are pertinent for the work planned and that safety measures will be effective. Thus, the work permit is based on a case-by-case risk assessment and does not strictly follow a checklist for different containment levels.

Different Government Departments (e.g., Ministries of Defense, Foreign Affairs, Social Affairs, and Health) and agencies are usually involved in the process of funding high-containment facilities, seeking competent advice from several national expert agencies e.g. Swedish Institute for Communicable Disease Control,¹ National Veterinary Institute,² Swedish Defense Research Agency,³ National Board of Health and Welfare,⁴ universities, and committees.

Standards

The EU Directive 2000/54/EC⁵ and the SWEA statute book AFS 2005:1⁶ provide the overarching regulatory framework for construction of containment facilities. In addition there are numerous EN standards for construction and engineering. It is not mandatory for EU Member States to follow the EN standards, but Sweden has adopted most EN standards as national standards (SIS), which makes compliance necessary.

AFS 2000:05⁷ and AFS 2005:01⁸ specify how and when to apply to SWEA for permission to work with risk class 3 and 4 biological agents. Application has to be renewed every 3-5 years. There are no specific laboratory biosecurity regulations in Sweden but the AFS 2000:5 and 2005:1 dealing extensively with biosafety cover most aspects of laboratory biosecurity. The Ministry of Defense with the Swedish Defense Research Agency as an adviser ensures compliance with the Biological and Toxin Weapons Convention but with little application for laboratories. There is a dialogue between the Swedish Institute for Communicable Disease Control (SMI), where the CL 4 facility is located, and the Swedish Security Service,⁹ who informs SMI about any changes in the terrorism situation that may call for additional biosecurity provisions. SWEA has 10 regional inspectorate offices with general work environment inspectors, but biosafety competence is rather scarce and containment facilities are rarely inspected.

Laboratory-associated Infections (LAI)

There is mandatory notification to SWEA of work-related illness, including laboratory-associated infections, as well as of serious incidents with a potential for harm. Employers that run containment labs are required to have a system in place for internal reporting and authority notification when deemed necessary. The employer is required to investigate incidents and accidents and take corrective actions. SWEA can inspect any time they choose to do so. In practice this is done if the safety representative, mandatory in every work place with >5 employees, requests an inspection or if misconduct is suspected. According to the Work Environment Act, the employer is always accountable for the conditions in the workplace and legal actions can be taken if safety precautions are not in place. Imprisonment is possible but is extremely rarely effectuated.

Actions to prevent laboratory incidents

The Swedish Institute for Communicable Disease Control (SMI) and other Government expert authorities together with the profession conduct awareness raising events. SMI initiated the Nordic Biosafety Network in 2004. Work is underway to foster the implementation of The Laboratory Biorisk Management standard, CWA 15793.¹⁰ As in other countries, underreporting and lack of communication of laboratory incidents is an unresolved issue.

No specific actions have been taken on the national level to increase laboratory biosecurity, but there is an increased awareness of the need for precautionary measures among government agencies, the profession, and the management of containment facilities. An example of this is the publication Handbook of Applied Biosecurity for Life Science Laboratories¹¹ issued by the Stockholm International Peace Research Institute (SIPRI).

The European Commission has adopted an EU CBRN Action Plan¹² on strengthening chemical, biological, radiological, and nuclear (CBRN) security in the European Union. The overall goal is an all-hazard approach to reduce the threat of and damage from CBRN incidents of accidental, natural, or intentional origin, including acts of terrorism. The Action Plan has set up a number of goals in three areas: prevention, detection, and preparedness and response. The implementation of the EU CBRN Action Plan is now in its second year. Sweden is a keen participant in frequent meetings with Member States experts.

E6. COUNTRY OVERVIEW FOR TURKEY: BIOSECURITY LAWS AND REGULATIONS IN TURKEY

Hüseyin Avni Öktem, Ph.D. Middle East Technical University, Turkey

What high-containment biological (high BSL) laboratories exist in your country? What are the facilities’ main goals and priorities?

• The Ministry of Agriculture and Rural Affairs has four BSL facilities that are focused on animal diseases and vaccines.
• The Refik Saydam National Public Health Agency, Sihhiye/Ankara has one lab that focuses on infectious disease surveillance and prevention on a national basis.
• The Gulhane Medical Military Academy, Etlik/Ankara has a medically focused lab.
• The TUBITAK Marmara Research Center, Genetic Engineering and Biotechnology Institute, Gebze/Kocaeli has a research-focused lab.

What government organizations are responsible for the safety and security of high BSL laboratories?

The Ministry of Agriculture and Rural Affairs, General Directorate of Protection and Control and the Ministry of Health are responsible.

If there are high BSL laboratories in your country, are there established criteria for deciding:

a.

Whether or not to establish such facilities?

b.

Where to place such facilities?

c.

What research will be done in such facilities?

d.

What scientific, technical, and management advice is available to governments when making their decisions?

In Turkey there are rules and legislation about establishing and running analysis laboratories for food, animal feed, water, genetic testing, etc. These analysis laboratories are controlled by the Ministry of Agriculture and Rural Affairs and by the Ministry of Health. However, there is not yet legislation about establishing a high BSL laboratory in Turkey.

What standards exist for high BSL laboratories for:

e.

Engineering and construction?

f.

Licensing?

g.

Safety and security?

h.

Regular oversight and re-certification?

As there isn’t any established legislation for such laboratories, internationally established standards and guidelines (CDC’s Office of Safety, Health and Environment, National Institute of Health, World Health Organization’s Center for Applied Biosafety, etc.) are being used and followed.

Have there been any accidents at high BSL labs in your country?

i.

If yes, how and why did the accidents occur?

j.

How, to whom, and when are they reported?

k.

Who has authority to investigate accidents?

l.

What disciplinary or legal actions can be taken?

No accidents.

Have any steps been taken to increase security at high BSL facilities? If so, by whom (i.e., regulation, voluntary measures, individual laboratory practices)?

Security has been increased through individual laboratory practices.

Furthermore, as a result of an increase in research and commercial activities in biotechnology along with the commencement of membership negotiations with the European Union, Turkey has passed biosecurity-related legislation in recent years. Among these laws, the most relevant ones are given below.

Biosecurity-related laws and directives:

• Directive About the Field Studies of Transgenic Culture Plants (05/08/1998)
• The Cartagena Protocol on Biosafety (01/24/2004)
• Directive on Import, Process, Export, Control, and Regulation of Genetically Modified Organisms for Human and Animal Consumption (10/26/2009)
• Biosecurity Law (no.5997 – 09/26/2010)
• Directive on Operational Procedures and Principles of Biosecurity Board and Committees (no.27671 – 08/13/2010)
• Directive on Genetically Modified Organisms and Their Products (no.27671 – 08/13/2010)

Like their equivalents in other countries, biosecurity laws and directives in Turkey are mostly concerned with Genetically Modified Organisms (GMOs) and their distribution, use, import, and export. One of the earliest examples of such a directive was the “directive about the field studies of transgenic culture plants” by the Ministry of Agriculture and Rural Affairs (MARA) in 1998. This directive aimed to prevent the import of GMOs for human consumption that had not first being tested in a field study in Turkey. In addition, all GMOs to be imported were required to have a certification from a country having biosecurity legislation.

In the absence of a national law on biosecurity, in 2000, Turkey signed The Cartagena Protocol on Biosafety and it was ratified in the Turkish Parliament in 2003. In 2002, Turkey started to prepare a “Biosecurity Law” in compliance with The Cartagena Protocol and received project money from the United Nations Environment Program—The Global Environment Facility (UNEP-GEF) to prepare a draft. This project, entitled “Project on the Development of the National Biosafety Framework of Turkey” was started on September 18th, 2002 and finished on March 18th, 2005. Later in 2009, MARA finalized the Biosecurity Law, and it was passed by parliament in 2010. The law does not cover medical or cosmetic products that are approved by the Ministry of Health, but bans the production and release of any GMOs and their use in baby food. The Law also specifies terms of 5 to 10 years of imprisonment for unlawful acts related to unapproved use of GMOs.

A “Biosecurity Board” involving scientists and experts was established by a directive from MARA and held its first meeting on September 27th, 2010. The Board started a web site called “Information Exchange in Biosecurity” at http://www.tbbdm.gov.tr. So far, the Biosecurity Board has had five meetings and accepted only one GMO (A2704-12 soy bean for use in animal feed). The board contains 9 members that are selected by the related ministries as follows: 4 by the Ministry of Agriculture and Rural Affairs (2 from the Ministry, 1 from a University, 1 from a NGO), 2 by the Ministry of Forestry and Hydraulic Works, 1 by the Ministry of Health, 1 by the Ministry of Science, Industry, and Technology, and 1 by the Ministry of Economy.

Directives concerning BSL Labs are under development.

E7. HIGH-CONTAINMENT LABORATORIES IN UKRAINE: LOCAL RESOURCES AND REGULATIONS

Olena Kysil^1,2, Serhiy Komisarenko^{1 1}Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine and ²National Taras Shevchenko University of Kyiv, Ukraine bs.conf@gmail.com

What high-containment biological (high BSL) laboratories exist in your country? What are the facilities’ main goals and priorities?

There are over 4,000 registered microbiological laboratories in Ukraine, but only 2 of them have a permit to work with microorganisms of the first pathogenic group, 402 laboratories have a permit to work with the microorganisms of the second pathogenic group, and all others are allowed to work only with microorganisms of the third and forth pathogenic groups. Here it is necessary to note that the classification of pathogenic organisms and therefore classification of the laboratories in Ukraine differs from the international one. It is inverted (i.e., in Ukraine “one” is the highest risk and “four” is the lowest risk) and also has some additional differences. That is why when speaking about high-containment laboratories according to Ukraine’s official classification we need to consider the laboratories that have a permit to work with the microorganisms of the first and the second pathogenic groups. At the same time it is not possible to say that a laboratory that has a permit to work with microorganisms of the first pathogenic group in Ukraine is equivalent to an international BSL-4 lab or that one working with microorganisms of the second pathogenic group is equivalent to a BSL-3 lab.

According to the available data, there are no laboratories in Ukraine that fulfill BSL-4 requirements. One of the laboratories that has a permit to work with the microorganisms of the first pathogenic group did, however, recently undergo an international audit as a BSL-3 laboratory and received a preliminary positive evaluation. This is one of the laboratories of the SI (State Institution) “Ukrainian I. I. Mechnikov Anti-Plague Research Institute” of the Ministry of Health of Ukraine (Odessa), which is responsible for the identification of especially dangerous biological pathogens. This laboratory was reconstructed and technically updated up to the BSL-3 level through a cooperative agreement between the United States Department of Defense and the Ministry of Health of Ukraine that started in 2005. The collaboration focuses on preventing the spread of technologies, pathogens, and knowledge that can be used in the development of biological weapons. The updated laboratory serves as Interim Central Reference Laboratory with a depozitarium (pathogen collection). According to Ukrainian regulations, it has a permit to work with both bacteria and viruses of the first and second pathogenic groups. A second laboratory of the SI “Ukrainian I. I. Mechnikov Anti-Plague Research Institute” of the Ministry of Health of Ukraine also has a permit to work with microorganisms of the first pathogenic group, but it is not updated to the BSL-3 level. This laboratory works only with the especially dangerous infections of bacterial etiology. The third laboratory upgraded to the BSL-3 level belongs to the Central Sanitary Epidemiological Station of the Ministry of Health of Ukraine. This laboratory was updated within the State program and the above-mentioned cooperative agreement between Ukraine and the United States. It has a permit to work with microorganisms of the second pathogenic group and is intended for work with especially dangerous infections.

According to the information received from the Central Regime Commission, the main authority that is responsible for the registration of microbiological laboratories in Ukraine, among the 402 laboratories that have permits to work with microorganisms of the second pathogenic group, 37 are subordinate to the Ministry of Health of Ukraine. Out of these 37 laboratories, 6 laboratories belong to research institutions, and therefore their main goals are scientific and practical investigations, while 31 laboratories belong to the Sanitary Epidemiological Service of Ukraine. These 31 laboratories are responsible for epidemiological and diagnostic investigations. Three hundred sixty two laboratories that have a permit to work with microorganisms of the second pathogenic group are subordinate to the Ministry of Agrarian Policy and Food of Ukraine. Out of them, 358 laboratories are responsible for diagnostic investigations, while 4 belong to research institutions and perform scientific and practical investigations. The four laboratories of the National Academy of Agrarian Sciences of Ukraine, which have a permit to work with microorganisms of the second pathogenic group, are research oriented. The one laboratory of the Ministry of Defense of Ukraine that has a permit to work with microorganisms of the second pathogenic group performs diagnostic investigations.

What government organizations are responsible for the safety and security of high BSL laboratories?

According to the existing regulations, the main authority that is responsible for the registration of microbiological laboratories and their biosafety and biosecurity is the Central Regime Commission, which works together with regional Regime Commissions of the State Sanitary Epidemiological Service of Ukraine and regional chief state sanitary doctors of Ukraine (according to the State Sanitary Rules 9.9.5.035-99 and 9.9.5-153-2008).

If there are high BSL laboratories in your country, are there established criteria for deciding:

a.

Whether or not to establish such facilities?

b.

Where to place such facilities?

c.

What research will be done in such facilities?

d.

What scientific, technical, and management advice is available to governments when making their decisions?

In the case of state subordination of a new laboratory, the decision to establish it or not needs to be taken by the State based on recommendations of a Ministry or a state institution. Then, for example, the decision to establish a new laboratory needs to be included into a state program. To our knowledge there are no established criteria for such a decision.

What standards exist for high BSL laboratories for:

a.

Engineering and construction?

b.

Licensing?

c.

Safety and security?

d.

Regular oversight and re-certification?

These are the main regulations that set the high BSL laboratory standards:

1.

The State Sanitary Rules 9.9.5.035-99 “The safety of work with microorganisms of the I-II pathogenic groups” (1999)

2.

The State Sanitary Rules 9.9.5.-080-02 “The rules of the organization and the safety of work at microbiological laboratories (departments, units)” (2002)

3.

The State Sanitary Rules 9.9.5-153-2008 “The organization of laboratories’ work in the case of investigation of materials containing the biological pathogenic agents by molecular-genetic methods” (2008)

4.

The Order of Ministry of Health of Ukraine N183 from 14.12.1992 “On regime of work with pathogenic microorganisms”

5.

The Order of Ministry of Health of Ukraine N452 from 06.11.2001 “On strengthening of anti-epidemical regime of work at microbiological laboratories”

The project of the Regulation of Cabinet of Ministers of Ukraine, proposed by the Ministry of Health of Ukraine “The question of permit issue for work with the microorganisms of the I-IV pathogenic groups for microbiological laboratories and the functioning of regime commissions on biosafety” (2008) is currently undergoing public discussion.

Have there been any accidents at high BSL labs in your country?

According to the information received from the Central Regime Commission during the last twenty years, there were no registered accidents at high-containment laboratories in Ukraine.

Have any steps been taken to minimize high BSL laboratory accidents?

A few virology laboratories of the State Sanitary Epidemiological Service of Ukraine were updated with equipment to fulfill international biosafety requirements for working with poliomyelitis, measles, and influenza as part of a World Health Organization (WHO) Program. The laboratories of the Central Sanitary Epidemiological Station of the Ministry of Health of Ukraine and the SI “Ukrainian I. I. Mechnikov Anti-Plague Research Institute” of the Ministry of Health of Ukraine were also reconstructed and equipped as part of an agreement with the United States. Over the next years, a few of the regional Sanitary Epidemiological Stations of the Ministry of Health of Ukraine and laboratories of the National Academy of Agrarian Sciences of Ukraine are also scheduled to be updated as part of the same agreement with the United States.

It is also important to mention activities connected with training of laboratory personnel. For example, intensive training programs are running as part of an agreement with the United States. There is also a new Training Centre on Biosafety in Odessa functioning as part of SI “Ukrainian I. I. Mechnikov Anti-Plague Research Institute.” Its creation was supported by Canada’s Global Partnership Program through the Science and Technology Center in Ukraine (STCU) to ensure modern biosafety and biosecurity training programs.

There are also some projects to increase the biosafety and biosecurity, which are being run by individual laboratories. For example, the Central Sanitary Epidemiological Station of the Ministry of Health of Ukraine laboratory that works with especially dangerous infections is implementing the Laboratory Biorisk Management Standard CWA 15793:2008 with support from Canada through STCU.

All these steps aim to minimize the risk of accidents and to increase laboratory security.

Have any steps been taken to increase security at high BSL facilities? If so, by whom (i.e., regulation, voluntary measures, individual laboratory practices)?

Besides the above-mentioned activities, which are intended to both minimize accidents and increase of security at high BSL facilities, there is also a project to strengthen the education of life scientists on biosafety, biosecurity, and dual-use issues. The project is run by the Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine in close collaboration with the University of Bradford with support of Canada through STCU. The aim of the project is to strengthen support for the prohibition of the misuse of the modern life sciences by pioneering the formulation and implementation of a national system of biosafety, biosecurity, and dual-use issues education.

E8. HIGH-CONTAINMENT LABORATORIES—UK CASE STUDY

Dr. Neil Davison, Science Policy Centre, the Royal Society Dr. Filippa Lentzos, BIOS Centre, London School of Economics

Royal Society contribution to a project of the Committee on International Security and Arms Control (CISAC) and the Board of Life Sciences at the US National Academy of Sciences: “Anticipating Biosecurity Challenges of the Global Expansion of High-containment Biological Laboratories”

What high-containment biological research facilities exist in your country?

The UK has both Biosafety Level 3 (BSL-3) and Biosafety Level 4 (BSL-4) laboratories. In the UK these are referred to as Containment Level 3 and 4 (CL3 & CL4). Most work with dangerous pathogens is carried out in Government and Research Council laboratories.¹

There are approximately 600 laboratories around the UK that are built to operate at BSL-3. Of these around 150 are in research institutes and 150 at universities, although differentiating between research institutes and university laboratories is difficult. There are around 75 BSL-3 laboratories operated by private companies. A large proportion of BSL-3 capacity is held by a small number of universities and research institutes, e.g. two universities have 84 BSL-3 laboratories between them; and one institute has 60 BSL-3 laboratories. The National Health Service (NHS) has 170 BSL-3 laboratories mainly for diagnostics.²

Table E8-1 shows data collected by the Health and Safety Executive (HSE) for the number of organisations with BSL-3 laboratories and their operators as of December 2007. Note that an organisation is at the employer level (e.g. University of Oxford), and a given organisation may have multiple facilities.³

In December 2007, HSE figures showed ten sites in the UK with BSL-4 laboratories as shown in Table E8-2. These figures referred to seven government or government sponsored research institutes, one government clinical diagnostic site, and two commercial veterinary vaccine manufacturers.⁴ However, as of April 2009 there is only one privately operated BSL-4 site since the Intervet Schering-Plough laboratory in Middlesex, which previously carried out research on Newcastle disease, has now closed. This brings the total number of BSL-4 sites to nine.

Of the eight government sites, five can operate at BSL-4 for human pathogens (ACDP4), although only four actually operate at this level, and three at BSL-4 for animal pathogens (SAPO4). Seven sites have facilities to work with infected animals.⁵ The facilities at each site vary in size from a single room to multiple suites or even individual buildings of BSL-4 laboratories.⁶ All BSL-4 facilities are located in the South East of England, ranging from rural settings to suburban areas and cities (there are three BSL-4 sites in or near London).⁷ In addition to these BSL-4 laboratories for research and diagnostics, there are also two High Security Disease Isolation Units (HSDUs) for the care of patients with viral haemorrhagic fevers, such as Ebola or Lassa. One is in Coppetts Wood, London, which would also be used for a postmortem requiring BSL-4, and the other is under development at the Royal Victoria Infirmary, Newcastle.⁸

Details of eight of the UK BSL-4 sites are provided in the UK Government Confidence Building Measure (CBM) submission to the Biological and Toxin Weapons Convention (BTWC), as shown in Table E8-3.⁹

A 2008 review of the UK’s BSL-4 laboratories, Chaired by Professor George Griffin and sponsored by the Health Protection Agency, the Medical Research Council, the Biotechnology and Biological Sciences Research Council, and the Department for Environment, Food and Rural Affairs, identified six building or renovation plans for BSL-4 facilities that were in planning or under consideration as of October 2008:

“Two of these are in major universities, one involving the up-grading of a yet to be licensed SAPO3 facility to a SAPO4 level, the other, the construction of a completely new ACDP [Advisory Committee on Dangerous Pathogens] CL4 laboratory.”¹⁰

2 What government organizations are responsible for safety and security of high-containment biological (high BSL) laboratories?

The Health and Safety Executive (HSE)¹¹ is the main government authority that regulates standards and compliance relating to general health, safety and the environment including most matters relating to biological agents, biosafety, and genetic modification. HSE fulfils advisory, regulatory, and enforcement roles.

HSE has sole responsibility for inspections and enforcement at facilities handling dangerous human and animal pathogens and Genetically Modified Microorganisms (GMMs) in the UK.¹² Until 2008 the Department for Environment, Food and Rural Affairs (Defra) regulated standards and compliance for animal and plant diseases, and it continues to license premises for work with animal pathogens under the Specified Animal Pathogens Order (SAPO).¹³ The Home Office is responsible for standards and compliance relating to biosecurity.¹⁴ The Advisory Committee on Dangerous Pathogens (ACDP) provides independent scientific advice (see Section 3).

The June 2008 report of a House of Commons inquiry on Biosecurity in UK research laboratories expressed concern that there was no ministerial oversight of biosecurity and recommended:

“… that in view of the cross-cutting nature of these issues, the Government establish a ministerial group to meet periodically to discuss issues of biosecurity. A single Minister, for example the Minister for Science and Innovation, should take responsibility for co-ordinating biosecurity and the provision of high-containment laboratories and should act to convene this ministerial group and the inter-agency body we have recommended be set up.”¹⁵

The government response to this recommendation noted:

“Where scientific and technical issues are involved, the Chief Scientific Advisers’ Committee is best placed to oversee cross-cutting issues and receive reports from the interagency group from time to time.

We agree with the Select Committee that a collective Ministerial overview would be appropriate, at least until Ministers are confident that coordination by officials and Chief Scientific Advisers is working well. We will therefore establish a Ministerial group, to be convened when the need arises.”¹⁶

Regulations and associated responsibilities are currently undergoing significant changes. In the aftermath of the foot and mouth disease (FMD) outbreak in Surrey in 2007 (see Section 5), a single regulatory framework for human and animal pathogens will replace relevant elements of existing regulations.¹⁷ Consultations on the new regulations, termed The Biological Agents and Genetically Modified Organisms (Contained Use) Regulations, are now complete, and it is expected that the new regulations will be introduced in 2012.¹⁸ The Advisory Committee on Dangerous Pathogens (ACDP) (see Section 3) is producing guidance to accompany the new regulations that will encompass a common set of containment measures for human and animal pathogens.¹⁹ The guidance is currently in draft form.²⁰

As of July 2011, and prior to the introduction of the new regulations, biosafety in UK laboratories is covered by three pieces of legislation:²¹

• The Control of Substances Hazardous to Health Regulations 2002 (COSHH)²²
  COSHH regulations come under the European Communities Act 1972 and the Health and Safety at Work etc Act 1974.²³ COSHH regulations are wide-ranging and are not limited to regulation of dangerous pathogens. They are enforced by HSE.²⁴ Under COSHH, pathogens are classified into Hazard Groups 1-4 based on the risk to human health as defined in The Approved List of Biological Agents.²⁵ This list is produced in consultation with the Advisory Committee on Dangerous Pathogens (ACDP).²⁶ Biosafety level categories under COSHH are often referred to as ACDP1-4. COSHH is primarily aimed at preventing exposure of workers to dangerous pathogens and places duties on employers to carry out risk assessments and ensure that exposure is prevented or controlled.²⁷
• The Specified Animal Pathogens Order 2008 (SAPO)²⁸
  SAPO regulates the use of animal pathogens and until recently was administered by Defra. SAPO is aimed at preventing the escape of pathogens from the laboratory and not with the protection of laboratory workers. It is a licensing system that specifies conditions for handling animal pathogens following inspection of the laboratory and documentation. Licenses are usually valid for five years. Conditions cover: safe containment and disposal; the areas of the laboratory in which various types of work may be done; and the people responsible for the work.²⁹ Following recommendations of the Callaghan Review,³⁰ HSE is now responsible for inspection and enforcement across the UK while Defra remains responsible for licensing. SAPO was based on the ACDP 1-4 recommendations (animal pathogens are consequently classed in four categories: SAPO1-4³¹) and the regulations covering work with animal pathogens was therefore interlined with those covering human pathogens even before the decision to develop a single regulatory framework.
• The Genetically Modified Organisms (Contained Use) Regulations 2000 [GMO(CU)]³²
  GMO(CU) regulations³³ come under the European Communities Act 1972 and the Health and Safety at Work etc Act 1974. GMO(CU) regulates genetically modified pathogens, categorising them in Class 1-4, according to an assessment of risks to both the worker and the environment (thereby differing from COSHH and SAPO). HSE and Defra are responsible for this regulation in England and Wales, and HSE and the Scottish Executive in Scotland.³⁴

Table E8-4 below shows data from HSE for the number of organisations (for BSL-3) and number of sites (for BSL-4) working with dangerous pathogens and their regulation as of December 2007. (Note: These data were provided before HSE took on responsibility for SAPO).

The Home Office is responsible for biosecurity in UK laboratories. The regulatory framework is Part 7 and Schedule 5 of the Anti-terrorism Crime and Security Act 2001 (ATCSA),³⁵ which is implemented by the National Counter-Terrorism Security Office (NaCTSO),³⁶ a police unit reporting to the Association of Chief Police Officers (ACPO). ATCSA allows the police to impose security measures in laboratories handling dangerous pathogens and toxins included on a list of just over 100 pathogens in Schedule 5, which was extended in 2007 to include animal pathogens.³⁷ ATCSA covers around 400 laboratories including university and hospital laboratories.³⁸ Guidelines governing these measures are provided in restricted circulation documents published jointly by the Home Office and NaCTSO: “Security Standards for Laboratories”; and “Personnel Security Measures for Laboratories.”³⁹

ATCSA requires laboratories to:

• Register with the Home Office their holdings of Schedule 5 substances.
• Inform the police of the security measures in place and the personnel who have access to the Schedule 5 substances in certain circumstances.
• Ensure that Schedule 5 substances and the premises in which they are kept, stored, worked on, and disposed of are secure.
• Ensure that access to said substances is authorised and controlled.⁴⁰

If there are BSL laboratories in your country, are there established criteria for deciding:

a. Whether or not to establish such facilities?

Establishment of new BSL-3 and BSL-4 facilities is at the discretion of the relevant organisation, company, or government department. Consulting HSE at an early stage is considered advisable when building new BSL-3 and BSL-4 facilities. For BSL-3 facilities, the organisation is encouraged to contact HSE, and for BSL-4 HSE is always consulted. HSE has the power to prevent the construction of a BSL-4 laboratory if it considers the plans for its construction, operation, or maintenance to be unsafe.⁴¹

The 2008 House of Commons inquiry recommended that “…HSE be a statutory consultee in any planning application for a CL3 or CL4 laboratory.”⁴² The report also urged “…HSE to engage as early as possible with those building and operating high-containment facilities to avoid resorting to enforcement action.”⁴³ The UK government has stated that it does not intend to amend current requirements for planning permission but that, in the development of the new single regulatory framework (SRF), consideration will be given to the information that should be provided to HSE and the extent of consultation required for a new facility or change of use of an existing facility.⁴⁴

What criteria are used to select the placement of such facilities?

There are no universal criteria used to select the placement of high-containment facilities. The location of BSL-3 and BSL-4 laboratories is part of an overall risk assessment that would consider other factors including the availability of scientific and maintenance staff and proximity to emergency services.⁴⁵ The 2008 House of Commons inquiry concluded “there is no reason in principle why CL4 laboratories should not be built in urban areas, provided that the correct risk assessment is undertaken and biorisk is managed appropriately. As each case will be unique, we recommend that such applications be treated on an individual basis.”⁴⁶

As regards the highest level of containment, an October 2008 independent review of UK BSL-4 facilities Chaired by Professor George Griffin concluded:

“The geographical locations of the existing high-containment facilities have arisen for historic operational reasons and few opportunities exist to alter this situation. When such opportunities do arise then decisions on their location should be based on a robust, multi-faceted risk assessment in which microbiological science and all aspects of security, safety, and public opinion are considered and on the existence of good links to academic centres of excellence.”⁴⁷

The review emphasised the importance on taking into account public opinion when locating or renovating high-containment facilities.

HSE’s guidance, Biological agents: The principles, design and operation of Containment Level 4 facilities, notes that local authorities are responsible for adequate planning and public consent and that those designing the BSL-4 laboratory may want to consider conducting a local public consultation.⁴⁸

HSE provides more specific guidance on factors that influence the positioning of a BSL-4 building at a given location including: headroom; access; daylight and visibility; utilities; and air handling.⁴⁹ The guidance also notes:

“The CL4 [BSL-4] facility will consist of either a separate building or a clearly demarcated and isolated zone within a building. Activities can be separated by locating the laboratory away from main public thoroughfares of the building. The rooms in the unit should be arranged to ensure passage through the changing and decontamination area before entering rooms where work is done with HG4 [Hazard Group 4] agents.”⁵⁰

b. What criteria are used to decide what research will be done in such facilities?

Decisions on research to be undertaken are taken by the organisation, company, or government department that is responsible for the laboratory. There are specific requirements for containment measures for BSL-3 and 4 laboratories, as detailed in Section 4. ACDP guidance, Biological agents: Managing the risks in laboratories and healthcare premises,⁵¹ provides criteria for selecting appropriate control measures for different types of research and different pathogens.

c. What scientific, technical, and management advice is available to governments when making their decisions.

Advice and guidance is provided to the UK government by the Biological Agents Unit at HSE.⁵² Independent scientific and technical advice is provided by the Advisory Committee on Dangerous Pathogens (ACDP), a non-departmental public body with a Chairman and up to 17 members comprising scientific experts, employer representatives, and employee representatives. ACDP’s terms of reference are:

“To advise the Health and Safety Executive, and Ministers for the Department of Health and the Department for Environment, Food and Rural Affairs, and their counterparts under devolution in Scotland, Wales and Northern Ireland, as required, on all aspects of hazards and risks to workers and others from exposure to pathogens.”⁵³

ACDP’s two main areas of work are: “Production of guidance relating to safety at work and protection of public health; and Provision of advice to Government on the formulation and implementation of policy and legislation, relating to specific pathogen risks and their impact.” ⁵⁴

There are three main guidance documents in current use, which were produced by ACDP and published by HSE:

• The management, design and operation of microbiological containment laboratories (2001),⁵⁵ aimed at those responsible for the management and operation of BSL2 and BSL-3 laboratories.
• Biological agents: Managing the risks in laboratories and healthcare premises (2005),⁵⁶ aimed at the healthcare sector; and
• Biological agents: The principles, design and operation of Containment Level 4 facilities (2006),⁵⁷ which is aimed at high-hazard containment facilities, mainly those that present a risk to human health under COSHH. Genetically modified and animal pathogens are discussed only in the context of human health.

As discussed in Section 2, ACDP and HSE are currently developing guidance to accompany the new single regulatory framework to be introduced during 2012.⁵⁸

4   What standards exist for BSL laboratories?

In the UK there are legal requirements under COSHH, SAPO, GMO(CU), and ATCSA (see Section 2). These are supported by guidance from ACDP (see Section 3 (d)). A new single regulatory framework for biosafety, which will replace GMO(CU) and elements of COSHH and SAPO, is under development for introduction during 2012. ATCSA related standards for biosecurity regulated by the Home Office will remain the same.

a) For engineering and construction?

The minimum containment requirements under COSHH regulations for BSL-3 and BSL-4 laboratories are summarised in ">Table E8-5, which is taken from the ACDP guidance Biological agents: Managing the risks in laboratories and healthcare premises.⁵⁹

The minimum containment requirements under COSHH, SAPO and GMO(CU) regulations for work in BSL-4 laboratories are shown in Table E8.6, which is taken from the ACDP guidance The Principles, Design and Operation of Containment Level 4 Facilities. ⁶⁰

These two ACDP guidance documents provide further guidance for the design, construction, and operation of BSL-3 and BSL-4 laboratories. They also refer to publications that provide more detailed information on laboratory construction: Richmond, J Y (ed) (2000) Anthology of Biosafety II – BSL 2 Facility design considerations. American Biological Safety Association; and Richmond, J Y (ed) (2002) Anthology of Biosafety V – BSL 4 Laboratories. American Biological Safety Association.

The ACDP note that:

“…it must be remembered that each CL4 [BSL-4] laboratory will be unique and that the number of publications and people (e.g. architects, designers and engineers) with experience of building a CL4 facility will be limited. Consequently, extensive liaison and consultation between all parties, including regulators, at a very early stage is highly recommended for a successful build – the aim being to eliminate problems at the design stage rather than rectifying problems once the facility is built.”⁶¹

b) For licensing? (Also see Section 2)

SAPO is a licensing regime, work covered by COSHH requires notification and, work under GMO (CU) requires permission.⁶² Laboratory work covered by ATCSA requires notification.

There is no formal licensing system under COSHH regulations, which are enforced by HSE. However, there is a requirement for those wishing to work on dangerous pathogens in the laboratory to notify and receive acknowledgement from HSE.⁶³ Evidence submitted by the government to the 2008 House of Commons inquiry noted:

“In addition to using specific control measures, those working with dangerous pathogens need to notify HSE at least 20 days in advance of any planned work where HG [hazard group] 2, HG3 and HG4 are used for the first time, at particular premises. Notification is also required of the subsequent use of certain organisms (i.e. those in HG3 and HG4 and those in HG2 that are listed in Part V of Schedule 3 of COSHH are used for the first time).

Although this is not an approval system, HSE requires the notification to include sufficient information to demonstrate that duty holders have identified hazards associated with the organism which might arise from carrying out the work.”⁶⁴

Defra remains responsible for licensing under SAPO (although HSE is now responsible for oversight). SAPO prohibits the possession or introduction of any animal pathogens listed in Part I of the Schedule, or any carrier of that pathogen, except under license. These are primarily exotic diseases that can affect farmed livestock and poultry. No license is needed to possess a pathogen listed in Part II of the schedule but its introduction to any animal is prohibited except under license. Conditions in licenses also place restrictions on domestic transfer of animal pathogens.⁶⁵ Government evidence to the House of Commons inquiry provides more details on SAPO licensing:

“The SAPO licensing process includes inspection of the applicants’ laboratories and review of supporting documentation (i.e. the operating procedures for work, risk assessment and appropriate containment measures) prior to the licence being issued. Licences are usually valid for five years. Inspections of laboratories licensed under SAPO may be carried out at any time to ensure full compliance with license conditions and the Order.”⁶⁶

GMO (CU) regulations require anyone carrying out genetic modification to conduct a risk assessment for human health and the environment and assign containment accordingly. Activities are assigned a risk class equating to the containment level (1-4). Prior to Class 2, 3 or 4 activities commencing, a notification must be submitted including an assessment of the hazards and planned containment measures. HSE and Defra review these notifications and request additional information where necessary. Written consent from HSE is required before work in class 3 or 4 begins.⁶⁷

Under ATCSA, laboratories are required to register their holding of Schedule 5 substances with the Home Office and provide information to the police on their security measures and, in certain conditions, personnel. Liaison with laboratories is carried out by police Counter Terrorism Security Advisors (CTSAs) from the National Counter-Terrorism Security Office (NaCTSO). Security requirements are dependent on the organism(s) being handled. BSL-4 laboratories have extensive security measures with extremely limited access and all staff must have security clearances. Access to pathogens is restricted at BSL-3 laboratories, which are also subject to security measures and are provided with advice on staff security checking.⁶⁸

c) For safety and security?

There are regulatory requirements for biosafety, covered by COSHH, SAPO and GMO(CU), and biosecurity, covered by ATCSA (see Section 2) and supporting guidance from ACDP (see Section 3 (d)). Minimum containment requirements are outlined in Section 4 (a).

In addition there are relevant standards and guidance around staffing and training. ACDP highlights the important role of Biological Safety Officers/Advisors (BSOs/BSAs):

“The recruitment of a biological safety advisor (BSA) is pivotal in ensuring management are provided with sufficient information and advice to ensure risks related to biological agents are either controlled or prevented.”⁶⁹

The 2008 House of Commons inquiry on biosecurity noted that there was “…widespread support for a more high profile role for BSOs and for giving them professional status.”⁷⁰

Training is essential for work at high containment and employers are required to provide this under health and safety law and specific regulations such as COSHH. The House of Commons inquiry found that training could be better coordinated⁷¹ and, following the Griffin review, the government’s inter-agency group that is reviewing staffing of high-containment laboratories will also address training issues.⁷²

The House of Commons inquiry also reviewed the issue of vetting staff, noting that:

“…security clearance for scientists working with dangerous pathogens is still not harmonised in the UK and for Home and EU staff or students security-vetting is not always a prerequisite for work with dangerous pathogens.”⁷³

Those working in government laboratories are subject to government vetting programmes but standards in universities, Research Council institutes, and the private sector vary.⁷⁴ The National Counter-Terrorism Security Office (NaCTSO) liaises with laboratories on security checks under ATCSA.

The Foreign and Commonwealth Office (FCO) administers the Academic Technology Approval Scheme (ATAS),⁷⁵ which was introduced November 2007 as a replacement for the Voluntary Vetting Scheme. It requires all non European Union (EU) students applying for certain postgraduate programmes at UK universities to receive an ATAS certificate specific to their course and place of study before they apply to enter the UK or extend their stay. ATAS covers a wide range of science and engineering Masters and Doctorate research programmes and a more limited number of taught Masters courses.⁷⁶

According to Nature, the FCO had rejected 100 applications in the period up to November 2008, representing 0.5 percent of around 20,000 applications.⁷⁷ There is limited publicly available information about the operation of ATAS. An internal FCO review concluded that ATAS is a useful contribution to security at modest cost but noted concerns that handling times for applications are taking significantly longer than the planned ten working day processing time. The review recommended that the FCO ATAS Unit should conduct a biannual review of subject coverage to coincide with UK universities’ own review.⁷⁸

d) For regular oversight and re-certification?

The requirement for notifying HSE under COSHH regulations does not automatically lead to an inspection but the information is used to inform inspections and HSE expect to inspect BSL-4 laboratories once a year and BSL-3 laboratories at least once every three years.⁷⁹ However, the House of Commons inquiry observed that:

“…we received evidence that inspections are often infrequent unless problems are reported and that the frequency should increase. Concerns have also been expressed that the HSE may not have sufficient resources, especially with the new burden envisaged by the Callaghan Review, to inspect sufficiently,…”⁸⁰

Under SAPO, inspections may be carried out at any time to ensure compliance with the licence conditions. In April 2008 HSE took over from Defra as the lead inspector and regulator.⁸¹

Under GMO (CU) all activities in Class 4 or novel genetic modification activities are brought to the attention of the Scientific Advisory Committee for Genetic Modification (SACGM), which provides advice to HSE on the risk assessment that has been submitted. Site inspection may be required if novel containment requirements are proposed. HSE issues consent for work to proceed once satisfied with the risk assessment and proposed containment measures.⁸²

Under ATCSA, laboratories working with Schedule 5 agents must notify the Home Office and will then be visited by Counter Terrorism Security Advisors (CTSAs). Visits are used to assess physical security and make recommendations. CTSAs produce a written assessment including security advice, which is then provided to the laboratory. Any security improvements required are specific to the laboratory. Often advice is focused on personnel security and procedures with information about security checks and monitoring of staff. (Police can request the details of those with access to Schedule 5 materials if they have specific intelligence.) CTSAs visit registered laboratories once a year or more often if security improvements are required. As of July 2008 there had been issues at two sites, both related to a shortage of funds to improve security at university facilities.⁸³

5 Have there been any BSL accidents in your country?

a) If yes, how and why did accidents at high-containment facilities occur?

Foot and mouth disease outbreak in Surrey, UK in August 2007

Pirbright is the site of an Institute for Animal Health (IAH) laboratory and the vaccine manufacturer Merial Animal Health Ltd. A company called Stabilitech that carried out work with FMDV in a laboratory within the IAH facility left the Pirbright site in 2008. The preliminary investigation of an outbreak of FMD in August 2007 indicated that the Pirbright site was the likely source.⁸⁴ The Health and Safety Executive (HSE) was then tasked with investigating: “potential breaches of biosecurity at the Pirbright site; whether such breaches may have led to a release of any specified animal pathogen; whether any such breaches had been rectified to prevent future incidents.”⁸⁵ The December 2007 report of the investigation concluded that wastewater containing live virus leaked out from the drainage pipes and contaminated the surrounding soil. The investigation found evidence of long term damage and leakage from the waste system, including cracked pipes, tree branches breaching pipes, and unsealed manholes. The virus is thought to have spread by vehicles and been exacerbated by mud and slurry due to heavy rainfall in July 2007.⁸⁶

Merial were engaged in large-scale FMDV vaccine production and the waste from this process containing live virus was passed into the site drainage system along with smaller quantities from IAH and Stablitech operations, as permitted under the Defra licence. However, the investigators found that the condition of the site drainage system breached biosecurity for the site as a whole and did not meet requirements for BSL-4 containment. Ownership of the drainage system rests with IAH but the investigators found a difference in opinion between IAH and Merial over responsibility for maintenance of a key section of pipe. (Detailed information about the investigation can be found in the December 2007 report by the HSE, Final report on potential breaches of biosecurity at the Pirbright site 2007.)⁸⁷

In addition to recommending a review of the regulatory framework for animal pathogens (see Section 2 and Section 5 (e)), HSE made specific recommendations to the site operators on: whether a high-containment laboratory could be sealed for fumigation; the testing of filters; the need to investigate whether liquid waste could be effectively sterilized; and improvements to the effluent drainage system.⁸⁸

Another well-documented example from the UK is the Birmingham University Medical School smallpox outbreak in 1978.

b) How, to whom and when are they reported?

The Reporting of Injuries, Diseases and Dangerous Occurrences Regulations 1995 (RIDDOR)⁸⁹ requires laboratories to report to HSE certain accidents and near misses involving high hazard biological agents⁹⁰ that pose a risk to human health. It covers wild-type human pathogens, zoonotic pathogens, and genetically modified versions of these. RIDDOR requires reporting of infections due to work with live or dead humans or animals, exposure to body fluids, or any potentially infected material derived for any of these. A separate report is required for any release or escape of a biological agent likely to cause severe human disease (i.e., hazard group 3 or 4 biological agents or Class 3 or 4 GMMs). Infections that could have been acquired outside work are not reportable. The following types of accidents require reporting:

• Accidents where the person dies, suffers major injury, or is absent or unable to work for more than three days;
• Accidents where a person not at work suffers an injury and is taken to hospital;
• A person suffering one of the specified work-related diseases; and
• A “dangerous occurrence”, which may not necessarily result in injury but has potential to cause significant harm. These encompass any accident or incident that causes or could have caused the release of a biological agent that could cause severe human disease (i.e., hazard group 3 and 4 agents and certain hazard group 2 agents).⁹¹

Guidance on RIDDOR last updated in 2008 is provided by HSE: A guide to the Reporting of Injuries, Diseases and Dangerous Occurrences Regulations 1995.⁹²

In addition to RIDDOR requirements for a given accident, there are requirements under GMO(CU)⁹³ regulations to report certain accidents involving Genetically Modified Organisms (GMOs) to HSE, described as “… an accident involving a significant and unintended release of genetically modified organisms in the course of an activity involving genetic modification which presents an immediate or delayed hazard to human health or the environment.”⁹⁴ Such accidents might include:

• “the spillage of any Class 3 GMM outside of a microbiological safety cabinet (MSC) or other primary container;
• a major spillage of a Class 3 GMM within a MSC;
• the spillage of any Class 2 GMM outside of a MSC or other primary container, where it is thought likely that an individual or the environment could have been exposed during the spill or during decontamination;
• the release or escape of a GMO, other than a GMM that could cause harm to human health, for example, by acting as a novel disease reservoir;
• infection (classical) of a person with a (replication competent) GMM, as this constitutes a significant and unintended release.”⁹⁵

After an accident notification, HSE is required to investigate and provide a report to the European Commission.⁹⁶

HSE must also be notified of any accident while working with specified animal pathogens, which has or may have caused the release of a specified animal pathogen that could cause serious disease in susceptible animals. For any release into the environment, Defra should also be notified.⁹⁷

c) Who has authority to investigate accidents?

HSE has authority for investigating accidents.

d) What disciplinary or legal actions can be taken?

Under COSHH and GMO(CU) where significant breaches are identified, HSE, “Specialist Inspectors can use a full range of enforcement powers conferred by the Health and Safety at Work Act 1974, which include stopping work activities, issuing notices requiring specific improvements by specific dates and prosecution.”⁹⁸

Under SAPO, if HSE inspectors identify non-compliance under the licence conditions they can recommend the license is amended, suspended, or revoked by Defra. Any prosecution would be undertaken by the relevant local authority, when alerted to non-compliance by inspectors.⁹⁹

Under ATCSA, the police CTSAs can demand security requirements, and failure to comply with these is a criminal offence.¹⁰⁰

e) Have any steps been taken to minimize BSL laboratory accidents?

Following the HSE investigation of the Pirbright FMD outbreak,¹⁰¹ the government instigated a review of the safety of facilities handling FMDV, carried out by Professor Brian Spratt and published in August 2007, which highlighted a potential conflict of interest for Defra as regulator, licensor, and inspector of the facilities and also their major customer.¹⁰²

Subsequently, the government asked Sir Bill Callaghan to carry out a “…review of the regulatory framework for handling animal pathogens and to make recommendations to Government for changes that would strengthen the regulation of animal pathogens.”¹⁰³ In addition, the Prime Minster commissioned Dr Iain Anderson to lead an independent review of the lessons learned from the response to the 2007 outbreak.¹⁰⁴

The Callaghan Review – accepted in full by the government – recommended a three-phase approach to changes leading towards a single regulatory framework (SRF) for human and animal pathogens.¹⁰⁵

The recent status of the changes is summarised in a June 2009 HSE paper:

“Phase 1, for HSE to formalise support to Defra and the Devolved Administrations for SAPO inspections, is now complete; Phase 2 saw changes made to the Specified Animal Pathogens Order (SAPO) to designate HSE as the inspection and enforcement body by means of Agency Agreements with Defra and the Devolved Administrations. These arrangements were implemented successfully and are working well.

We are now working on the third and most complex phase of the project that will deliver:

a.

the SRF comprising a single set of regulations to govern work with human and animal pathogens based on a Legislative Reform Order (LRO) to provide HSE with the viruses to make regulations in relation to animal pathogens;

b.

a common set of containment measures based on advice from ACDP (HSE is leading the work);

c.

appropriate cost recovery and integrated notification systems.”¹⁰⁶

These new regulations, to be introduced in 2012, are termed The Biological Agents and Genetically Modified Organisms (Contained Use) Regulations.¹⁰⁷ They will replace will replace GMO(CU) and elements of COSHH and SAPO, and will be accompanied by guidance from ACDP, which is currently in draft form.¹⁰⁸

Government evidence to the 2008 House of Commons inquiry provided some information on the inspection activity that followed the 2007 FMD outbreak:

“Following the publication of the investigation report following the 2007 outbreak of FMD, HSE and Defra released a Safety Alert on 7 September 2007. This was aimed at all high-containment laboratories, to draw attention to the issues arising from the investigation. In addition, HSE and Defra committed to undertake a programme of inspections.

The first phase of the Safety Alert inspection programme focused on CL4 facilities where work is undertaken with Hazard Group (HG) four dangerous pathogens, including both human and animal pathogens.

The inspections revealed no breaches of the legislation and no formal enforcement action was taken. This process has provided both the regulatory bodies and the operators of the laboratories with the assurance that their facilities are well managed. The inspections have also provided a useful opportunity to provide advice and guidance on good practices. HSE will continue this series of Safety Alert inspections to consider CL3 facilities based on risk. The inspections will begin in January 2008 and will be completed by the end of the year.”¹⁰⁹

Another issue raised in the 2008 House of Commons inquiry was a concern over under-investment in certain UK high-containment laboratories, noting:

“We have observed at first hand the extent to which the quality of facilities can vary, even those designated CL4. Some of the UK’s facilities are world-class; for example the state-of-the-art facilities at the DSTL, Porton Down. In contrast, we found other facilities, at IAH Pirbright and at the HPA in Porton Down, to be in need of significant investment given their age…”¹¹⁰

In July 2009 the BBSRC and the government announced £100 million in funding to be allocated to the redevelopment of the IAH facilities at Pirbright.¹¹¹

f) Have any steps been taken to increase security at BSL facilities?

In 2007 Schedule 5 of ATCSA was updated to include animal pathogens.¹¹² In July 2008, the government noted plans to review Schedule 5 of ATCSA every two years to update the list of agents covered, and also to review whether any further changes should be made to primary and secondary legislation.¹¹³

Acknowledgements

The Royal Society would like to thank the Advisory Group for reviewing this document:

• Professor Keith Gull FRS, Wellcome Trust Principal Research Fellow, Sir William Dunn School of Pathology, University of Oxford
• Dr John McCauley, Division of Virology, National Institute of Medical Research, Medical Research Council
• Sir John Skehel FRS
• Professor Geoffrey Smith FRS (Chair), Wellcome Principal Research Fellow and Head, Department of Virology, Imperial College London; and Chair, Royal Society Advisory Group on the Scientific Aspects of International Security (SAIS).
• Professor Robin Weiss FRS, Professor of Viral Oncology, University College London.

We would also like to thank Katie Wookey, intern at the Science Policy Centre in 2009, for conducting background research.

Please send any comments to: Dr Filippa Lentzos, BIOS Centre, London School of Economics, Houghton Street, London WC2A 2AE, UK; e-mail: f.lentzos@lse.ac.uk.

E9. UNITED STATES HIGH-CONTAINMENT BIOLOGICAL LABS AND REGULATIONS

United States National Research Council Staff

1. What high-containment biological research facilities exist in the United States?

Since 2001, the number of facilities that can conduct high-containment biological research (United States Centers for Disease Control [CDC] and Prevention Biological Safety 3 or 4 level—BSL 3-4) in the United States has increased and is expected to continue increasing in the immediate future as planned labs are completed and become operational (United States GAO, 2009a).

A rough estimate of the number of BSL-3 labs can be based on the number of labs registered with the Select Agent Program, the main regulatory program for United States high-risk biological research, which is described in the next section. As of 2010, 1,495 laboratories were registered with the Select Agent Program through the CDC (Kaiser, 2011). This provides only a rough estimate of the number of BSL-3 labs as some select agents can be handled at the BSL-2 level, while some pathogens that necessitate BSL-3 precautions are not select agents.¹ Also, some laboratories registered with the Select Agent Program reside outside of the United States.

In 2011, 6 United States entities collectively contained 8 laboratories operating at the BSL-4 level (Table E9-1). Six other BSL-4 laboratories were in the planning or construction phase, one of which will replace an existing laboratory (Table E9-2). BSL-4 facilities, such as the National Institutes of Health’s (NIH) small BSL-4 lab in Bethesda, Maryland, that currently operate only at a lower containment level (United States GAO, 2007) were not included in those totals.

Private companies, non-profits, academic institutions as well as state, local, and federal agencies maintain high-containment facilities. The Department of Defense (DOD), the Department of Homeland Security (DHS), and the Department of Health and Human Services (HHS) operate the main government facilities, sometimes through contracts with private organizations. DOD operates the United States Army Medical Research Institute for Infectious Diseases (USAMRIID).² DHS operates the new National Biodefense Analysis and Countermeasures Center (NBACC) through a contract with Battelle National Biodefense Institute and maintains the Plum Island Animal Disease Center, which is scheduled to be replaced eventually by the National Bio and Agro-Defense Facility (NBAF) in Manhattan, Kansas.³ HHS funds multiple BSL-3 facilities at the NIH and BSL-4 facilities at the CDC. In addition, HHS, through the National Institute of Allergy and Infectious Diseases (NIAID), partially funded construction of the Galveston and Boston University National Laboratories (BSL-4) and 13 BSL-3 Regional Biocontainment Laboratories (Table E9-3).⁴ These laboratories are distributed across the United States to conduct research and assist with public health efforts during emergencies. Additionally, HHS funds the Laboratory Response Network (LRN) that includes over 140 Reference Laboratories that have BSL-3 capabilities and can perform confirmatory testing.⁵ LRN Reference Laboratories include state and local public health labs as well as military, federal, and international (i.e., Canada, Australia, and United Kingdom) facilities.

2. What government organizations in the United States are responsible for oversight, safety, and security of high-containment biological (high BSL) laboratories?

No single government entity has total responsibility for the safety and security of high-containment laboratories (United States GAO, 2007; see page 4). Instead, oversight is provided by multiple organizations under a number of regulatory frameworks, including:

Select Agent Program

One of the major regulatory programs for high-containment labs in the United States is the Select Agent Program. The program was established in 1996 via the Antiterrorism and Effective Death Penalty Act (P.L. 104-132).¹ This law required the Department of Health and Human Services (HHS) to identify a set of organisms and toxins (“Select Agents”) that could be used for bioterrorist attacks and to regulate the transport of those pathogens. Later, the 2001 Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act (USA PATRIOT Act: P.L. 107-56) and the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (P.L. 107-188) added restrictions on the possession, use, and transfer of select agent pathogens and toxins. More information on the history of the Select Agent Program may be found in the National Research Council report on Responsible Research with Biological Select Agents and Toxins (NRC, 2009).

The current Select Agent Program covers two lists of pathogens and toxins. The agents on the HHS list are human health threats while those on the United States Department of Agriculture (USDA) list are animal and plant pathogens. Some agents are on both the HHS and USDA lists (overlap agents). The listed agents are to be reviewed every two years. The program also addresses two other areas—people who have access to select agents and facilities where select agents are used. Additionally, the program monitors the quantity of each agent held by each person at each facility. Scientists who conduct research with pathogens on the select agent list must undergo a background check called a Security Risk Assessment (SRA) with the Department of Justice (DOJ). These clearances are pathogen and institution specific, nontransferable, and valid for three years.² (Prior to June 1, 2011, clearances were valid for five years.) Facilities that possess or use select agents must develop and implement a security plan to protect the select agents from theft or improper access and identify a Responsible Official (RO). The RO has the authority and responsibility to ensure compliance with the regulations and report any incidents to the proper authorities.³ Depending on the pathogen, security plans are submitted either to CDC, USDA’s Animal and Plant Health Inspection Service (APHIS), or both for overlap pathogens. A plan must include a site-specific risk assessment, an agent-specific risk assessment, a threat assessment, a vulnerability assessment, and information about physical security, inventory control, and information systems control.⁴ CDC and APHIS conduct routine inspections every three years (annually for BSL-4 labs) and may conduct additional inspections at any time if an entity requests a change to its registration.⁵ During inspections, both APHIS and CDC use standardized checklists to ensure compliance.⁶ Any problems found during an inspection are reported to the institution and must be addressed. If, for example, CDC finds significant problems at a laboratory the following actions may be taken:

“Administrative actions: CDC can decide to suspend or revoke a registered entity’s certificate of registration (a suspension can be for all work at a registered entity or be specific to particular agents or particular types of experiments). Also, CDC can deny an entity’s application to possess, use, or transfer select agents;

Referral to HHS-Office of the Inspector General (OIG): CDC can refer possible violations of the select agent regulations to HHS-OIG. HHS-OIG can levy civil monetary penalties (up to $250,000 for an individual for each violation and up to $500,000 for an entity for each violation) or recommend criminal enforcement (imprisonment for up to five years, a fine, or both).

Referral to FBI: CDC can refer possible violations involving criminal negligence or a suspicious activity or person to the FBI for further investigation.”⁷

Through June 29, 2011, the HHS Office of Inspector General (OIG) had accepted a total of $2,127,000 from 16 different organizations to settle allegations of failure to comply with select agent regulations.⁸

To provide oversight of the CDC and APHIS’s implementation, the HHS and USDA OIG also conduct audits of the Select Agent Program. In a 2006 HHS audit of 15 universities, OIG found that 8 had inventory weaknesses, 6 had weak security plans, and 6 had access control problems.⁹ In a 2006 USDA audit, OIG found multiple weaknesses with the methods that APHIS was using to oversee and regulate the Select Agent Program including an inadequate review of security plans, use of an out-of-date list of individuals with access, and inadequate facility inspections (OIG, USDA, 2006).

In July 2010, Executive Order (EO) 13546, “Optimizing the Security of Biological Select Agents and Toxins in the United States,” created the Federal Experts Security Advisory Panel (FESAP), which was tasked to make recommendations to improve the Select Agents Program (Obama, 2010). To better match precautions to actual risks and reduce the impact of excessive security, EO 13546 instructed FESAP to (1) designate a subset of the select agent list as “Tier 1” agents and propose appropriate additional precautions and (2) consider whether any current select agents or toxins might be removed from the list. FESAP subsequently recommended 12 agents and toxins be designated as Tier 1 and 25 agents and toxins be removed from the list (FESAP, 2010).

NIH

The NIH’s Guidelines for Research Involving Recombinant DNA Molecules (RAC)¹⁰ provides oversight of laboratories whose investigators receive NIH funding and conduct experiments with recombinant DNA. While many experiments can be reviewed at the institutional level, some experiments require approval from the NIH. Many institutions that do not receive NIH funds voluntarily comply with the RAC guidelines as these are viewed as establishing best practices.

The RAC guidelines require institutions to establish an Institutional Biosafety Committee (IBC) to review research proposals that would require the use of recombinant DNA. Reviews should include an assessment of the procedures, facilities, and practices that would be used in the experiment. The IBC can approve proposals or make recommendations for modifying experiments. In addition, the institution must have a biological safety officer who periodically inspects laboratories, reports violations to the IBC, and prepares emergency plans for dealing with accidental exposures or spills.

OSHA

The Occupational Safety and Health Administration (OSHA) has several mandatory laboratory standards. For example, OSHA Standard 29 CFR 1910.1450 (Occupational Exposure to Hazardous Chemicals in the Laboratory) requires, among other things, that laboratories have a Chemical Hygiene Plan, mandatory employee training, personal protective equipment (PPE) for certain chemicals, and accessible material safety data sheets for all hazardous chemicals.¹¹ OSHA has also issued a Bloodborne Pathogen Standard, which provides guidance on preventing and responding to worker exposure to blood.¹² OSHA standards apply to public health laboratories and research laboratories at all biosafety levels.

Other Regulators

Many other government entities also play a role in regulation of biosafety and biosecurity in high-containment laboratories. The Departments of State, Commerce, and Treasury, for example, oversee export controls on biological products. Additionally, the Department of Transportation, the United States Postal Service, the International Civil Aviation Organization,¹³ and the International Air Transport Association¹⁴ all have regulations regarding the transportation of biological agents.

3. In the United States, are there established criteria for deciding:

a.

Whether or not to establish high-containment facilities?

b.

Where to place such facilities?

The decision to establish facilities depends on whether the facility is funded by the federal government or will be privately funded. There are, in general, no established criteria for privately funded facilities at universities or private sector institutions on when and where to build facilities. Government facilities or facilities at universities or elsewhere that are funded by the government are established based on the needs and research agendas of individual agencies, and no single government agency has the overall responsibility for determining needed laboratory capacity (United States GAO, 2009a). For example, the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 increased laboratory construction to support research efforts in several areas, including antimicrobial resistance and countermeasures research. Decisions on where to locate facilities are often made through a competitive bid process that solicits proposals from competing entities. The final location is picked based on the scientific and technical merit of a proposal as well as other factors, such as public support, transportation, and site accessibility. Risk assessments are conducted to assess the likelihood and consequences associated with possible pathogen releases (NRC, 2008). Construction of federally funded facilities also requires preparation of environmental impact statements and increasingly involves engaging the local community.

c.

What research will be done in such facilities?

High-containment biological laboratories are used for basic research, applied research, medical product testing and evaluation, and animal efficacy¹⁵ studies (United States GAO, 2007). The research done at government-funded facilities includes both investigator-proposed projects and projects proposed by the sponsoring agencies. Grants are awarded competitively. DOD, NIH, and other government entities fund research grants.

d.

What scientific, technical, and management advice is available to governments when making their decisions?

A number of groups and organizations provide advice on the subject including:

National Research Council

The National Research Council (NRC), which is a part of the National Academies, writes independent, expert reports to advise the government and increase public understanding on matters related to science, engineering, and medicine.¹⁶ The NRC has commented on risk assessments for several high-containment labs including facilities at Fort Detrick, Maryland (NRC, 2010a); Boston, Massachusetts (NRC, 2007); and Manhattan, Kansas (NRC, 2010b). The NRC has also issued a number of reports on biosafety and biosecurity.

NSABB

The National Science Advisory Board for Biosecurity (NSABB) was formed by 42 U.S.C. 217a, section 222 of the Public Health Service Act and is governed by the Federal Advisory Committee Act. The NSABB was created in response to the recommendations made in the 2004 NRC report, Biotechnology Research in an Age of Terrorism.¹⁷ It includes non-governmental voting members and non-voting members from 15 federal agencies and departments. Members’ areas of expertise cover a wide range of topics, including: microbiology, biodefense, food production, export controls, law, and others.¹⁸ The NSABB advises the Secretary of HHS and other government leaders on policies related to dual use research in the life sciences by issuing reports and recommendations. For example, in September 2011, NSABB released a report on Guidance for Enhancing Personnel Reliability and Strengthening the Culture of Responsibility (NSABB, 2011).

Working Group on Strengthening the Biosecurity of the United States

Executive Order 14386,¹⁹ Strengthening Biosecurity of the United States, created the Working Group on Strengthening the Biosecurity of the United States on January 9, 2009. The Secretary of Defense and Secretary of HHS chair the group, which also consists of the Director of National Intelligence, the Director of the National Science Foundation, the Attorney General, and the Secretaries of State, Commerce, Agriculture, Transportation, and Energy. The group reviewed existing laws, regulations, and practices and made recommendations to the President in November 2009 in a report titled National Strategy for Countering Biological Threats.²⁰

4. What standards exist for high biological containment laboratories in the United States for engineering and construction, licensing, safety, security, regular oversight, and certification?

General Standards

The CDC-NIH publication Biosafety in Microbiological and Biomedical Laboratories (BMBL), which is currently in its 5^th edition, has served as the standard code of practice for biosafety since 1984 (United States HHS, 2009). The BMBL provides guidance on all areas of biosafety and biosecurity including decontamination, transportation, containment level recommendations, and agent-specific practices. BMBL guidelines have been widely adopted and are mandatory for research conducted using federal grants. Noncompliance may result in the loss of funding (CRS, 2009). Federal laboratories, and most other facilities built using federal funds, are built to standards established by the funding agency. For example, to receive NIH money, laboratory engineering and construction must comply with the NIH Design Requirements Manual.²¹ Additionally, those laboratories that work with select agents or recombinant DNA must abide by those programs’ previously mentioned standards.

Training

Training is required for personnel whose labs fall under the jurisdiction of the OSHA standards, the NIH guidelines, or the Select Agent Program. Rather than being standardized, training is specialized to the agents, risks, and activities in which the trainee will engage. In the case of select agent work, refresher training must be provided annually (CRS, 2009). High-containment labs commonly supplement didactic training with mentored, within-laboratory training (Le Duc et al., 2008).

Many organizations provide resources and guidelines for biosafety and biosecurity training:

• The Sandia National Laboratories’ International Biological Threat Reduction Program aims to reduce biological threats worldwide by, among other things, promoting the responsible use of biological agents, equipment, and expertise and improving the understanding of accidental and deliberate biological risks.²²
• The CDC has online course modules and exercises for training in biosafety and biosecurity.²³
• University of Texas Medical Branch maintains the National Biocontainment Training Center that provides training in biosafety and biosecurity to United States and international students, as well as on-site fellowships offering mentored training for individuals preparing for work at BSL-4 and for containment laboratory managers and engineers.²⁴
• Yale Center for Public Health has online course resources for biosafety training based on a course taught at the school, designed in part for those interested in implementing biosafety and biosecurity courses at their own facilities.²⁵
• Biosafety and animal safety training tools are available on the American Biological Safety Association (ABSA) website.²⁶

Commissioning Labs

Although there is no formal regulatory requirement for “commissioning,” when a new lab is built, a commissioning process may take place to ensure the lab meets safety standards. Agencies often contract out the process of commissioning a laboratory. Some agencies, for example the NIH, have specific checklists²⁷ and guidelines²⁸ for commissioning. A similar process occurs in other agencies and generally follows the recommendations of the BMBL. The commissioning documents are part of what must be presented during the select agent inspection that will eventually authorize high-containment labs to begin work with select agents (CRS, 2009).

5. Have there been any high-containment lab accidents in the United States?

a.

If yes, how and why did accidents at high-containment facilities occur?

b.

How, to whom and when are they reported?

c.

Who has authority to investigate accidents?

d.

What disciplinary or legal actions can be taken?

e.

Have any steps been taken to minimize BSL laboratory accidents?

Accidents, some of which result in laboratory-acquired infections (LAIs), occur regularly albeit at a low level in United States high-containment laboratories. For example, between 1982 and 2003, personnel at NIAID intramural laboratories worked with microorganisms for more than 3 million hours in BSL-3 laboratories or BSL-2 laboratories with BSL-3 practices and experienced a total of 29 exposures of which only 1 resulted in a clinical infection and 4 resulted in silent infections (Johnson, 2004). Laboratory accidents may result from either human error or equipment or engineering malfunction, and often the specific cause of a suspected LAI cannot be determined (Pike, 1979). FESAP recently proposed that occupational health programs be mandatory for individuals with access to Tier 1 agents, which would aid in identifying LAIs (FESAP, 2010). Table E9.4 contains a partial list of United States laboratory accidents. Additional information about LAIs observed in conjunction with United States containment lab work may be found in the NRC report, Protecting the Frontline in Biodefense Research: The Special Immunizations Program (NRC, 2011).

In the event of a theft, loss, or release of a select agent, the Select Agent Program currently requires a laboratory to notify the CDC and/or APHIS immediately (within 24 hours).²⁹ Appropriate federal, state, or local law enforcement must also be notified in the event of loss or theft; health agencies, such as local employee health services, must be notified if there is a risk of human infection. Additionally, the facility must submit APHIS/CDC Form 3 within seven days of the incident.³⁰ CDC or APHIS then conducts an investigation into the incident to determine the cause, actions that can be taken to mitigate future accidents, and whether further actions such as revocation of approval to work with select agents, fines, and/or potential criminal enforcement actions are needed.

Laboratories not in the select agent program typically have their own rules for accident reporting. For example, overt or potential exposures in BSL-3 and BSL-4 labs that occur in the course of research subject to NIH Recombinant DNA guidelines must be reported to the NIH Office of Biotechnology Activities immediately.

Increasingly, laboratories are making data on accidents publically available. For example, since 2002, University of Texas Medical Branch has published all incidents of laboratory accidents and potential exposures occurring in its research laboratories quarterly on its website.³¹

There have been several recent cases in which laboratories failed to report accidents in a timely manner. In 2006, Texas A&M did not report laboratory-acquired infections of Brucella and Coxiella burnetii that were later exposed through a Freedom-of-Information Act (FOIA) request.³² The CDC ultimately shut down select agent research at the laboratory until all problems identified in the subsequent investigation were addressed and the university agreed to pay a $1 million fine (Kaiser, 2008). At Boston University in 2004, three individuals who worked with a vaccine strain of Francisella tularensis (not a select agent) became ill with tularemia.³³ While two of the cases occurred in May and one in September, none was reported to the public health authorities until November. An investigation revealed that their stock of the vaccine strain had became contaminated by unknown means with Type A F. tularensis, which is a select agent. OSHA proposed fines of $8,100 for each of Boston University and Boston Medical Center Corporation for their failure to ensure proper use of personal protective equipment.³⁴ The lack of transparency at Boston University has greatly increased public concern about the new National Emerging Infectious Diseases Laboratory, for which the United States government is preparing additional risk assessments with advice from the National Research Council.³⁵

6. Have any steps been taken to increase security at high biological containment facilities?

While select agent rules do not mandate specific physical security requirements, BSL-4 laboratories are increasingly employing visible 24/7 armed guards, controlled access, vehicle barriers, and closed-circuit television monitoring (United States GAO, 2009b). Additionally, since 2008 many Department of Defense containment laboratories have been subject to Army Regulation 50-1, which established a biological ‘surety’ program that defines criteria for evaluating personnel reliability (Department of the Army, 2008).

Additionally, FESAP made a number of security recommendations that will be considered during the next revision of the Select Agent Regulations (FESAP, 2010). In particular, FESAP:

• Defined appropriate personnel reliability practices, including provisions for on-going monitoring, for individuals with access to Tier 1 agents and toxins and for individuals with access to other select agents and toxins;
• Specified physical and cyber security requirements for facilities with Tier 1 agents and for facilities with other select agents and toxins; and
• Recommended that facilities document protocols for shipping, storing, and receiving select agents and toxins.

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Footnotes

1

www​.biosafety-europe.eu.

2

http://eur-lex​.europa​.eu/LexUriServ/LexUriServ​.do?uri=OJ:L:2000​:262:0021:0045:EN:PDF.

1

Op. cit. see note 2

2

http://eur-lex​.europa​.eu/LexUriServ/LexUriServ​.do?uri=OJ:L:1998​:330:0013:0031:EN:PDF

3

Op. cit. see note 2

4

http://eur-lex​.europa​.eu/LexUriServ/LexUriServ​.do?uri=OJ:L:2009​:125:0075:0097:EN:PDF

5

http://www​.who.int/csr​/resources/publications​/biosafety/WHO_CDS_EPR_2006_6.pdf.

6

http://www​.fao.org/ag​/againfo/commissions​/docs/genses38/Appendix_10.pdf.

7

Op. cit. see note 2

8

http://register​.consilium​.europa.eu/pdf/en​/09/st15/st15505-re01co02.en09.pdf.

9

ftp://ftp​.cenorm.be/PUBLIC​/CWAs/wokrshop31/CWA15793.pdf.

1

E.A. Stavskiy, N.B.Cherny, A.A. Chepurnov, S.V. Netesov, Anthology of Some Biosafety Aspects in Russia (up to 1960), in Anthology of biosafety V. BSL-4 laboratories, J.Y. Richmond, Editor. 1999, American Biological Safety Association: Mundelein, IL. p. 29-91.

2

WHO. World Health Centers Global Database. [cited April 28, 2011]; Available from: http://apps​.who.int/whocc/Search.aspx.; State Research Center of Virology and Biotechnology-Vector. [cited 5 May 2011]; Available from: http://www​.vector.nsc​.ru/DesktopDefault.aspx?lcid​=9&tabindex​=1&tabid=52.

3

[cited October 26, 2011]; Available from: http://www​.who.int/influenza​/gisrs_laboratory​/h5_reflabs/h5_reference​_laboratories/en/index.html

4

[cited May 23, 2011]; Available from: http://www​.influenza​.spb.ru/en/influenza​_surveillance_system_in_russia​/who_national​_influenza_centre/.

5

OIE. List of Centres: OIE -World Organization for Animal Health. [cited April 28, 2011]; Available from: http://www​.oie.int/our-scientific-expertise​/collaborating-centres​/list-of-centres/.

6

OIE. List of Laboratories: OIE -World Organization for Animal Health. [cited April 28, 2011]; Available from: http://www​.oie.int/our-scientific-expertise​/reference-laboratories​/list-of-laboratories/.

7

http://old​.rospotrebnadzor​.ru/department/regulations/ (Charter of Rospotrebnadzor)

8

International Health Regulations -2005. http://www​.who.int/ihr/en

9

Russian State Order #60: http://www​.rg.ru/2006​/02/17/monitoring-dok.html.

10

Russian State Order #88: http://old​.rospotrebnadzor​.ru/docs/order/?id=1832.

11

Russian State Order #88: http://old​.rospotrebnadzor​.ru/docs/order/?id=1832.

12

Russian State Order #88: http://old​.rospotrebnadzor​.ru/docs/order/?id=1832.

13

Russian State Order #88: http://old​.rospotrebnadzor​.ru/docs/order/?id=1832.

14

Russian State Order #88: http://old​.rospotrebnadzor​.ru/docs/order/?id=1832.

15

Russian Sanitary Regulations for special and other dangerous pathogens of 1-2 pathogenicity groups: http://www​.lytech.ru/articles_31.htm.

16

E.A. Stavskiy, B. Johnson, R.J. Hawley, J.T. Crane, N.B. Cherny, I.V. Renau, S.V. Netesov, Comparative Analysis of Biosafety Guidelines of the USA, WHO, and Russia (Organizational and Controlling, Medical and Sanitary- Antiepidemiological Aspects). Applied Biosafety, 2003. 8(3): p. 118-

17

Russian Sanitary Regulations for special and other dangerous pathogens of 1-2 pathogenicity groups: http://www​.lytech.ru/articles_31.htm.

18

Russian Sanitary Regulations for special and other dangerous pathogens of 1-2 pathogenicity groups: http://www​.lytech.ru/articles_31.htm. (page 12)

19

E.A. Stavskiy, B. Johnson, R.J. Hawley, J.T. Crane, N.B. Cherny, I.V. Renau, S.V. Netesov, Comparative Analysis of Biosafety Guidelines of the USA, WHO, and Russia (Organizational and Controlling, Medical and Sanitary- Antiepidemiological Aspects). Applied Biosafety, 2003. 8(3): p. 118-

20

Russian Sanitary Regulations for special and other dangerous pathogens of 1-2 pathogenicity groups: http://www​.lytech.ru/articles_31.htm.

1

S. Ya. Gaidamovich, A. M. Butenko, and H. V. Leschinskaya. Human laboratory Acquired Arbo-, Arena-and Hantavirus infections. Journal of American Biological Safety Association. -2000. -V.5 (1)-P. 5-11.

2

L. A. Akinfeeva, O. I. Aksionova, I. V. Vasilevich, Z. I. Gin’ko, K. A. Zar’kov, N. M. Zybavichene, L. R. Katkova, O. P. Kuzovlev, V. I. Kuzubov, L. I. Lokteva, E. I. Ryabchikova. A case of Ebola hemorrhagic fever. Infektsionnye bolezni.-2005-No.1-P.85-88.

3

Netesov, S.V. The Current Situation with Education in Biosafety and Biosecurity in Russia. in Situation and Perspectives of Education in the Field of Biotechnology, Biosafety and bioethics at the Novosibirsk State University and other Russian Universities. 2009. House of Scientists, Novosibirsk, Russia.

4

Note verbale dated 26 October 2004 from the Permanent Mission of the Russian Federation to the United Nations addressed to the Chairman of the Committee. November 2, 2004, Permanent Mission of the Russian Federation to the United Nations.

5

Second report of the Russian Federation on the implementation of Security Council resolution 1540 (2004). 2004, Permanent Mission of the Russian Federation to the United Nations. (page 6)

6

Second report of the Russian Federation on the implementation of Security Council resolution 1540 (2004). 2004, Permanent Mission of the Russian Federation to the United Nations; National Research Council (United States). Committee on Prevention of Proliferation of Biological Weapons., The Biological Threat Reduction Program of the Department of Defense: from foreign assistance to sustainable partnerships. 2007, Washington: National Academies Press. ix, 109 p.

7

National Research Council (United States). Committee on Prevention of Proliferation of Biological Weapons., The Biological Threat Reduction Program of the Department of Defense: from foreign assistance to sustainable partnerships. 2007, Washington: National Academies Press. ix, 109 p. (page 34)

8

Weaver, L.M., Biosafety and Biosecurity Activities of the International Science and Technology Center in the Republics of the Former Soviet Union: Accomplishments, Challenges, and Prospects. Applied Biosafety: Journal of the American Biological Safety Association, 2010. 15(2): pp. 56-59.

1

www​.av.se

2

http://eur-lex​.europa​.eu/LexUriServ/LexUriServ​.do?uri=OJ:L:2000​:262:0021:0045:EN:PDF

3

http://eur-lex​.europa​.eu/LexUriServ/LexUriServ​.do?uri=OJ:L:2009​:125:0075:0097:EN:PDF

4

http://www​.av.se/dokument​/inenglish/legislations/eng0501.pdf

5

http://www​.av.se/dokument​/inenglish/legislations/eng0005.pdf

6

Op. cit. see note 3

7

http://eur-lex​.europa​.eu/LexUriServ/LexUriServ​.do?uri=OJ:L:2010​:134:0066:0072:EN:PDF

1

www​.smi.se

2

www​.sva.se

3

www​.foi.se

4

www​.socialstyrelsen.se

5

Op. cit. see note 2

6

Op. cit. see note 4

7

Op. cit. see note 3

8

Op. cit. see note 4

9

www​.sakerhetspolisen.se

10

ftp://ftp​.cenorm.be/PUBLIC​/CWAs/wokrshop31/CWA15793.pdf

11

http://books​.sipri.org​/product_info?c_product_id=382

12

http://register​.consilium​.europa.eu/pdf/en​/09/st15/st15505-re01co02.en09.pdf

1

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 160-162.

2

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf pp Ev 162.

3

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf pp 24-25 & http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 52.

4

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 162.

5

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev162.

6

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf pp 24-25 & http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 162.

7

http://www​.hpa.org.uk​/web/HPAwebFile/HPAweb_C/1227688128129.

8

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf pp 24-25.

9

UK BWC CBM 2009: http://www​.unog.ch/80256EDD006B8954​/(httpAssets)​/5D42C16D75CA84D4C12575A0002A5A7A​/$file/BWC_CBM_2009_UK.pdf.

10

http://www​.hpa.org.uk​/web/HPAwebFile/HPAweb_C/1227688128129.

11

http://www​.hse.gov.uk/biosafety/.

12

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p 20 & http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 53 & http://www​.hpa.org.uk​/web/HPAwebFile/HPAweb_C/1227688128129.

13

http://www​.hse.gov.uk​/biosafety/callaghan.htm.

14

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf & http://www​.opbw.org/new_process​/mx2008/BWC_2008_MX_Docs​/BWC_MSP_2008_MX_WP​.6_En.pdf.

15

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p 31.

16

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/1111/1111.pdf p 9.

17

http://www​.hse.gov.uk​/biosafety/callaghan.htm.

18

Consultative document http:​//consultations​.hse.gov.uk/inovem/gf2​.ti/f/11362/306085.1/pdf/-/cd230.pdf & draft regulations http://www​.hse.gov.uk​/aboutus/meetings/committees​/acdp/080609​/acdp-92-p13a-annex1.pdf.

19

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf pp13-15.

20

Draft CU2010: http://www​.hse.gov.uk​/aboutus/meetings/committees​/acdp/080609​/acdp-92-p13a-annex1.pdf.

21

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 51 & http://www​.opbw.org/new_process​/mx2008/BWC_MSP_2008_MX_WP​.7_En.pdf.

22

http://www​.opsi.gov.uk​/si/si2002/20022677.htm.

23

http://www​.hse.gov.uk/legislation/hswa​.htm.

24

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p10.

25

http://www​.hse.gov.uk/pubns/misc208.pdf.

26

http://www​.dh.gov.uk/ab/ACDP/index.htm.

27

http://archive​.defra​.gov.uk/foodfarm/farmanimal​/diseases/atoz​/fmd/documents/callaghan-reviewreport071213.pdf.

28

http://www​.opsi.gov.uk​/si/si2008/uksi_20080944_en_1.

29

http://www​.hse.gov.uk​/news/archive/07aug/finalreport.pdf p11.

30

http://archive​.defra​.gov.uk/foodfarm/farmanimal​/diseases/atoz​/fmd/documents/callaghan-reviewreport071213.pdf.

31

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p.10.

32

http://www​.opsi.gov.uk​/si/si2000/20002831.htm.

33

http://www​.hse.gov.uk/biosafety/gmo/law​.htm.

34

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p.10.

35

http://www​.opsi.gov.uk​/acts/acts2001/ukpga_20010024_en_1.

36

http://www​.nactso.gov.uk/.

37

http://www​.nactso.gov​.uk/SiteCollectionDocuments​/AreasOfRisk​/Implementation%20Guidance%20for%20Labs​.pdf.

38

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p11 & http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev52.

39

http://www​.dh.gov.uk​/prod_consum_dh/idcplg​%3FIdcService%3DGET_FILE​%26dID%3D137088%26Rendition%3DWeb.

40

http://www​.hse.gov.uk​/aboutus/meetings/committees​/acdp/080609​/acdp-92-p13a-annex1.pdf.

41

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i​.pdfp34.

42

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i​.pdfp35.

43

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p22.

44

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/1111/1111.pdf p11.

45

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p34.

46

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p35.

47

http://www​.hpa.org.uk​/web/HPAwebFile/HPAweb_C/1227688128129 p17.

48

http://www​.hse.gov.uk/pubns/web09.pdf p9.

49

http://www​.hse.gov.uk/pubns/web09.pdf p33.

50

http://www​.hse.gov.uk/pubns/web09.pdf p41.

51

http://www​.hse.gov.uk​/biosafety/biologagents.pdf

52

http://www​.hse.gov.uk​/biosafety/infection.htm

53

http://www​.dh.gov.uk/ab/ACDP/index.htm

54

http://www​.dh.gov.uk/ab/ACDP/index.htm

55

http://www​.hse.gov.uk​/pubns/books/microbio-cont.htm

56

http://www​.hse.gov.uk​/biosafety/biologagents.pdf

57

http://www​.dh.gov.uk​/en/Publicationsandstatistics​/Publications​/PublicationsPolicyAndGuidance​/DH_4135258

58

http://www​.hse.gov.uk​/aboutus/meetings/committees​/acdp/080609​/acdp-92-p13a-annex1.pdf

59

http://www​.hse.gov.uk​/biosafety/biologagents.pdf

60

http://www​.hse.gov.uk/pubns/web09.pdf pp 14-16.

61

http://www​.hse.gov.uk/pubns/web09.pdf p 31

62

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p 13

63

http://archive​.defra​.gov.uk/foodfarm/farmanimal​/diseases/atoz​/fmd/documents/callaghan-reviewreport071213.pdf p 8

64

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 55

65

http://www​.opbw.org/new_process​/mx2008/BWC_MSP_2008_MX_WP​.7_En.pdf

66

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 57

67

http://archive​.defra​.gov.uk/foodfarm/farmanimal​/diseases/atoz​/fmd/documents/callaghan-reviewreport071213.pdf, http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 56

68

http://www​.opbw.org/new_process​/mx2008/BWC_MSP_2008_MX_WP​.6_En.pdf

69

http://www​.hse.gov.uk/pubns/web09.pdf p 22

70

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p 18

71

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p 46

72

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/1111/1111.pdf p 15

73

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p 46

74

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p 47

75

http://www​.fco.gov.uk​/en/about-us/what-we-do​/services-we-deliver/atas/.

76

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 61-62.

77

http://www​.nature.com​/news/2008/081107/full/news​.2008.1211.html.

78

Communication with ATAS Unit, FCO, August 2009.

79

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 55.

80

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p 20.

81

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 56.

82

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 56.

83

http://www​.opbw.org/new_process​/mx2008/BWC_MSP_2008_MX_WP​.6_En.pdf & http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 56-57.

84

http://www​.hse.gov.uk​/news/archive/07aug/pirbright.pdf.

85

http://www​.hse.gov.uk​/news/archive/07aug/finalreport.pdf.

86

http://www​.hse.gov.uk​/news/archive/07aug/finalreport.pdf & http://www​.opbw.org/new_process​/mx2008/BWC_MSP_2008_MX_WP​.7_En.pdf.

87

http://www​.hse.gov.uk​/news/archive/07aug/finalreport.pdf.

88

http://www​.hse.gov.uk​/news/archive/07aug/finalreport.pdf & http://www​.opbw.org/new_process​/mx2008/BWC_MSP_2008_MX_WP​.7_En.pdf.

89

http://www​.hse.gov.uk/riddor/.

90

http://www​.opsi.gov.uk​/SI/si1995/Uksi_19953163_en_5​.htm#sdiv3.

91

http://www​.hse.gov.uk​/aboutus/meetings/committees​/acdp/080609​/acdp-92-p13a-annex1.pdf.

92

http://www​.hse.gov.uk/pubns/priced/l73​.pdf.

93

https://www​.hse.gov.uk​/forms/genetic/index.htm.

94

https://www​.hse.gov.uk​/forms/genetic/cu3.pdf.

95

https://www​.hse.gov.uk​/forms/genetic/cu3.pdf.

96

http://www​.hse.gov.uk​/aboutus/meetings/committees​/acdp/080609​/acdp-92-p13a-annex1.pdf.

97

http://www​.hse.gov.uk​/aboutus/meetings/committees​/acdp/080609​/acdp-92-p13a-annex1.pdf.

98

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 58.

99

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 58.

100

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 57.

101

http://www​.hse.gov.uk​/news/archive/07aug/finalreport.pdf.

102

http://archive​.defra​.gov.uk/foodfarm/farmanimal​/diseases/atoz​/fmd/documents/spratt_final.pdf.

103

http://archive​.defra​.gov.uk/foodfarm/farmanimal​/diseases/atoz​/fmd/documents/callaghan-reviewreport071213.pdf.

104

http://webarchive​.nationalarchives​.gov.uk/20100807034701/http://archive​.cabinetoffice​.gov.uk/fmdreview/.

105

http://archive​.defra​.gov.uk/foodfarm/farmanimal​/diseases/atoz​/fmd/documents/callaghan-reviewreport071213.pdf.

106

http://www​.hse.gov.uk​/aboutus/meetings/hseboard​/2009/230609/p-jun-b09-57.pdf.

107

http://www​.hse.gov.uk​/aboutus/meetings/hseboard​/2009/230609/p-jun-b09-57.pdf.

108

Draft CU2010: http://www​.hse.gov.uk​/aboutus/meetings/committees​/acdp/080609​/acdp-92-p13a-annex1.pdf.

109

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360ii.pdf Ev 54.

110

http://www​.publications​.parliament.uk/pa​/cm200708/cmselect/cmdius/360/360i.pdf p 25.

111

http://www​.bbsrc.ac.uk​/news/archive/2009​/090727-pr-100-million-boost-for-animal-health-research.aspx.

112

http://www​.opsi.gov.uk​/si/si2007/uksi_20070926_en_1.

113

http://www​.opbw.org/new_process​/mx2008/BWC_MSP_2008_MX_WP​.6_En.pdf.

1

For a list of Select Agent Pathogens, see: http://www​.selectagents​.gov/resources/List​%20of%20Select%20Agents​%20and%20Toxins_111708.pdf. Accessed October 6, 2011.

2

To learn more about USAMRIID, see: http://www​.usamriid.army.mil/. Accessed October 6, 2011.

3

To learn more about NBACC see: http://www​.bnbi.org/. To learn more about NBAF see: http://www​.dhs.gov/nbaf. Accessed October 8, 2011.

4

Available at: http://www​.niaid.nih​.gov/LabsAndResources​/resources/dmid/NBL_RBL/Pages/site.aspx. Accessed October 6, 2011.

5

See: http://www​.bt.cdc.gov​/lrn/pdf/lrn-overview-presentation.pdf. Accessed October 6, 2011.

1

To view the law see: http://frwebgate​.access​.gpo.gov/cgi-bin/getdoc​.cgi?dbname=104​_cong_public_laws&docid​=f:publ132.104. Accessed October 6, 2011.

2

To learn more about SRAs, see: http://www​.selectagents.gov/sra.html. Accessed October 6, 2011.

3

See: http://www​.selectagents​.gov/resources/Session​%201%20-%20RO%20Responsibilities​.pdf. Accessed October 6, 2011.

4

For more information see: http://www​.selectagents​.gov/resources%5CSecurity​%20Information%20Document.pdf. Accessed October 6, 2011.

5

See: http://www​.hhs.gov/asl​/testify/2007/10/t20071004c.html. Accessed October 6, 2011.

6

To view the checklists see: http://www​.selectagents​.gov/Checklists.html. Accessed October 6, 2011.

7

See: http://www​.hhs.gov/asl​/testify/2007/10/t20071004c.html. Accessed October 6, 2011.

8

See: http://oig​.hhs.gov/fraud​/enforcement/cmp/agents_toxins.asp. Accessed October 6, 2011.

9

See: http://oig​.hhs.gov/oas​/reports/region4/40502006.pdf. Accessed October 6, 2011.

10

For the full NIH Guidelines for Research Involving Recombinant DNA Molecules, see: http://oba​.od.nih.gov​/oba/rac/Guidelines/NIH_Guidelines.htm. Accessed October 6, 2011.

11

Available at: http://www​.osha.gov/pls/oshaweb/owadisp​.show​_document?p_table​=standards&p_id=10106. Accessed October 6, 2011.

12

Available at: http://www​.osha.gov/pls/oshaweb/owadisp​.show​_document?p_table​=STANDARDS&p_id=10051. Accessed October 6, 2011.

13

For more information, see: http://www​.icao.int. Accessed October 6, 2011.

14

For more information, see: http://www​.iata.org. Accessed October 6, 2011.

15

Information about “Animal Rule” studies to demonstrate efficacy for Food and Drug Administration (FDA) product licensure may be found in 21 CFR Parts 314 and 601: http://www​.accessdata​.fda.gov/scripts/cdrh​/cfdocs/cfcfr/CFRsearch​.cfm?CFRPart=314 and http://www​.accessdata​.fda.gov/scripts/cdrh​/cfdocs/cfcfr/CFRsearch​.cfm?CFRPart=601. Accessed October 6, 2011.

16

See: http://www​.nationalacademies.org/about/. Accessed October 6, 2011.

17

To view the report, go to: http://www​.nap.edu/catalog​.php?record_id=10827. Accessed October 6, 2011.

18

For more information on the NSABB see: http://oba​.od.nih.gov​/biosecurity/PDF/NSABB​_Charter_508_accessible.pdf or http://oba​.od.nih.gov​/biosecurity/biosecurity.html. Accessed October 6, 2011.

19

To view the Executive Order see: http://edocket​.access​.gpo.gov/2009/E9-818.htm. Accessed October 6, 2011.

20

The report can be found at: http://www​.whitehouse​.gov/sites/default/files​/National_Strategy​_for_Countering_BioThreats.pdf. Accessed October 6, 2011.

21

See: http://orf​.od.nih.gov​/NR/rdonlyres/AF690C46-0388-4180-9603-3060F3078F5F​/25782/NIHDesignRequirementsManualver711.zip. Accessed October 6, 2011.

22

See: http://biosecurity​.sandia.gov/. Accessed October 6, 2011.

23

See: http://www​.cdc.gov/od​/ohs/biosecurity_training/page2790.html. Accessed October 6, 2011.

24

See: http://www​.utmb.edu/nbtc. Accessed October 6, 2011.

25

See: http://publichealth​.yale​.edu/ycphp/biosafety/biosafety.html. Accessed October 6, 2011.

26

See: http://www​.absa.org/trainingtools.html. Accessed October 6, 2011.

27

Department of Health and Human Services, National Institutes of Health, Biosafety Level 3-Laboratory Certification Requirements.

28

The NIH is currently working on a new version of The NIH Model Commissioning Guide. Section 1-7 of the NIH Design Requirements Manual discusses commissioning: http://orf​.od.nih.gov​/NR/rdonlyres/AF690C46-0388-4180-9603-3060F3078F5F​/25782/NIHDesignRequirementsManualver711.zip. Accessed October 6, 2011.

29

See: http://www​.selectagents​.gov/resources/CDC-APHIS​_Theft_loss_Release​_Information_Document.pdf. Accessed October 6, 2011.

30

CDC/APHIS Form 3 is available at: http://www​.selectagents.gov/TLRForm.html. Accessed October 6, 2011.

31

Safety and Security/Incident Reports. Available at: http://www​.utmb.edu/gnl/safety/report​.shtml. Accessed October 17, 2011.

32

To learn more about the Texas A&M incident see: http://www​.cidrap.umn​.edu/cidrap/content​/bt/bioprep/news/sep1907biolab.html and http://www​.sunshine-project​.org/TAMU/CDCTAMUReport.pdf. Accessed October 6, 2011.

33

See: http://www​.bphc.org/programs​/cib/environmentalhealth​/biologicalsafety​/forms%20%20documents​/tularemia_report_2005.pdf. Accessed October 6, 2011.

34

See: http://www​.osha.gov/pls/oshaweb/owadisp​.show​_document?p_table​=NEWS_RELEASES&p_id=11351. Accessed October 6, 2011.

35

To view the NAS report, see: http://www​.nap.edu/catalog​.php?record_id=12208. Accessed 6 October 2011.