WHO Consultative Meeting on

High/Maximum Containment
(Biosafety Level 4) Laboratories
Networking
Venue: International Agency for Research on
Cancer (IARC), Lyon, France, 13–15 December
2017

Meeting report
WHO/WHE/CPI/2018.40
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Contents

Abbreviations ............................................................................................................................ vi
Executive summary................................................................................................................ viii
Introduction ................................................................................................................................ 1
Global BSL-4 laboratories – unprecedented opportunities and unique challenges ................... 2
Update on the revision of WHO’s Laboratory biosafety manual .............................................. 3
Varying approaches to high-containment facilities ................................................................... 4
Update on BSL-4 facilities......................................................................................................... 5
Planned high-containment laboratories .................................................................................. 5
Nagasaki University, Japan ................................................................................................ 5
Chinese Center for Disease Control and Prevention BSL-4 Laboratory, China................ 6
Public Health England, United Kingdom .......................................................................... 6
High-containment laboratories under construction ................................................................ 6
Research Centre for Emerging Pathogens with High Infectious Risk, Pasteur Institute
Côte d’Ivoire ...................................................................................................................... 6
National Bio and Agro-Defense Facility, United States of America ................................. 7
Facilities at the Pirbright Institute, United Kingdom ......................................................... 7
National High Containment Facilities for Animal Diseases Control and Prevention,
Harbin, China ..................................................................................................................... 8
Recently constructed BSL-4 laboratories that are operational ............................................... 9
National High-level Biosafety Laboratory, China ............................................................. 9
Korea Centers for Disease Control and Prevention BSL-4 Laboratory, Republic of Korea
............................................................................................................................................ 9
Victorian Infectious Diseases Reference Laboratory, Australia ...................................... 10
BSL-4 laboratory at the Robert Koch Institute, Germany ............................................... 10
Established high-containment laboratories – moving to the future ..................................... 11
Australian Animal Health Laboratory, Australia ............................................................. 11
US Army Medical Research Institute of Infectious Diseases, United States of America11
New laboratories and public opinion: earning public trust and support .................................. 12
National Emerging Infectious Diseases Laboratories, United States of America................ 12
National Institute of Infectious Diseases Laboratory, Japan ................................................ 13
Activities of other organizations and high-containment laboratory networks ......................... 14
World Organisation for Animal Health ................................................................................ 14
iii
 International Experts Group of Biosafety and Biosecurity Regulators ................................ 15
Biosafety Level 4 Zoonotic Laboratory Network ................................................................ 15
Group of High Containment Laboratories Directors............................................................ 16
Efficient response to highly dangerous and emerging pathogens at EU level ..................... 16
European Research Infrastructure on Highly Pathogenic Agents ........................................ 17
Unique opportunities to advance global health enabled by high-containment facilities ......... 18
Integrated Research Facility, National Institute for Allergy and Infectious Diseases , United
States of America ................................................................................................................. 18
Microbial Containment Complex, National Institute of Virology, India ............................. 19
Centre de Recerca en Sanitat Animal, Institut de Recerca i tecnologia Agrolimentàries,
Spain ..................................................................................................................................... 20
Issues in biosafety and biosecurity in high-containment laboratories ..................................... 21
Establishing and maintaining biosafety and biosecurity: the National Bio and Agro-
Defense Facility, United States of America ......................................................................... 21
Cooperation between scientists and engineers on laboratory design: National Biosafety
Laboratory, Hungary ............................................................................................................ 21
Cabinet line systems: Public Health England, United Kingdom ......................................... 22
Evidence-based biosafety: BSL-4 OIE laboratory at the Institute of Virology, Centre for
Research in Veterinary and Agronomic Sciences, National Institute of Agricultural
Technology, Argentina ......................................................................................................... 23
Surge capacity: Animal and Plant Health Agency, United Kingdom .................................. 24
Training for high-containment laboratories: networks, requirements and opportunities ........ 25
BSL4ZNET .......................................................................................................................... 25
Public Health Agency of Sweden......................................................................................... 25
IEGBBR member countries ................................................................................................. 26
High-containment laboratories in Novosibirsk, Russian Federation ................................... 26
BSL-4 laboratory oversight...................................................................................................... 27
Introduction .......................................................................................................................... 27
Federal Select Agent Program, United States of America ............................................... 27
Regulators and institutional review committees in the promotion of responsible science,
Switzerland ...................................................................................................................... 28
Regulators’ perspective ........................................................................................................ 28
Operators’ perspective.......................................................................................................... 30
Pressing issues in sharing pathogens ....................................................................................... 31
Nagoya Protocol ................................................................................................................... 31

iv
 Shipping of Category A Infectious Substances .................................................................... 33
MTAs ................................................................................................................................... 33
Building confidence between high-containment laboratories and the global community:
cultivating a safety-oriented culture......................................................................................... 34
Public Health Agency of Sweden......................................................................................... 34
KCDC, Republic of Korea ................................................................................................... 35
CDC, United States of America ........................................................................................... 36
Biosafety controls for newly emerging pathogens in a limited-resources setting ................... 37
Collaboration between high-containment facilities and WHO: moving forward .................... 38
Creation of a community of practice .................................................................................... 38
Facility sharing ..................................................................................................................... 39
Mapping of training opportunities........................................................................................ 39
Sample sharing ..................................................................................................................... 39
International recognition of BSL-4 laboratories .................................................................. 39
Suggested future roles and responsibilities for WHO .......................................................... 40
Annex 1. Agenda ..................................................................................................................... 41
Day 1: Wednesday, 13 December ........................................................................................ 41
Day 2: Thursday, 14 December............................................................................................ 42
Day 3: Friday, 15 December ................................................................................................ 45
Annex 2. Summary of biosecurity level 4 (BSL-4) laboratories in the planning or operational
phases as of December 2017, based on available information ................................................ 46
Annex 3. Participants ............................................................................................................... 50
Argentina .............................................................................................................................. 50
Australia ............................................................................................................................... 50
Brazil .................................................................................................................................... 50
Canada .................................................................................................................................. 50
China .................................................................................................................................... 50
Côte d'Ivoire ......................................................................................................................... 51
Czech Republic .................................................................................................................... 51
Denmark ............................................................................................................................... 51
France ................................................................................................................................... 51
Germany ............................................................................................................................... 51
Hungary ................................................................................................................................ 51
India ...................................................................................................................................... 52
v
Italy....................................................................................................................................... 52
Japan ..................................................................................................................................... 52
Netherlands........................................................................................................................... 52
New Zealand ........................................................................................................................ 52
Republic of Korea ................................................................................................................ 52
Russian Federation ............................................................................................................... 52
Saudi Arabia ......................................................................................................................... 53
Senegal ................................................................................................................................. 53
South Africa ......................................................................................................................... 53
Spain ..................................................................................................................................... 53
Sweden ................................................................................................................................. 53
Switzerland ........................................................................................................................... 53
United Kingdom ................................................................................................................... 53
United States of America ..................................................................................................... 54
Other organizations .............................................................................................................. 54
International Expert Group on Biosafety and Biosecurity Regulation (IEGBBR) .......... 54
World Organization for Animal Health (OIE) ................................................................. 55
WHO Collaborating Centre for biosafety and biosecurity .............................................. 55
Rapporteur ............................................................................................................................ 55
World Health Organization .................................................................................................. 55
Headquarters .................................................................................................................... 55
Regional Office for Europe .............................................................................................. 56

vi
Abbreviations

AAHL Australian Animal Health Laboratory

ABSL-4 animal biosafety level 4
ACDP3 Advisory Committee on Dangerous Pathogens level 3
ASTM American Society for Testing and Materials
BBSRC Biotechnology and Biological Sciences Research Council (United Kingdom)
BSL4ZNET Biosafety Level 4 Zoonotic Laboratory Network
BSL-4 biosecurity level 4
BSL-3Ag biosafety level 3 agriculture
BMBL Biosafety in microbiological and biomedical laboratories
Cat A Category A (Infectious Substances)
CCHF Crimean Congo haemorrhagic fever
CDC Centers for Disease Control and Prevention (United States of America)
CEN European Committee for Standardization
CEPRIS Research Centre for Emerging Pathogens with High Infectious Risk (Côte
d’Ivoire)
CICVyA Centre for Research in Veterinary and Agronomic Sciences (Argentina)
China CDC Chinese Center for Disease Control and Prevention
CLC community liaison committee
CL4 containment level 4
CL4 Ag Containment Level 4 Agriculture
CReSA Centre de Recerca en Sanitat Animal (Spain)
CT computed tomography
ELISAs enzyme-linked immunosorbent assays
EMERGE Efficient Response to Highly Dangerous and Emerging Pathogens at EU Level
ERINHA European Research Infrastructure on Highly Pathogenic Agents
EU European Union
HEPA filters high-efficiency particulate air filters
HPAI highly pathogenic avian influenza
HVAC heating, ventilation and air conditioning

vi
IEGBBR International Experts Group of Biosafety and Biosecurity Regulators
INTA National Institute of Agricultural Technology (Argentina)
IRF Integrated Research Facility
ISO International Organization for Standardization
KCDC Korea Centers for Disease Control & Prevention (Republic of Korea)
MRI magnetic resonance imaging
MTAs material transfer agreements
NEIDL National Emerging Infectious Diseases Laboratories (United States of America)
OIE World Organization for Animal Health
PCR polymerase chain reaction
PET positron emission tomography
PIP Framework Pandemic Influenza Preparedness Framework
PPE personal protective equipment
PC4 Physical Containment Level 4
PHE Public Health England
RG Risk Group (1 through 4)
R&D Blueprint Research and Development Blueprint (WHO)
SAPO4 Special Animal Pathogens Order level 4
SARS severe acute respiratory syndrome
SOPs standard operating procedures
SPECT single photon emission computed tomography
SPF specific pathogen free
URS user requirement specification (document)
USAMRIID US Army Medical Research Institute of Infectious Diseases
VHP vaporized hydrogen peroxide
VIDRL Victorian Infectious Diseases Reference Laboratory (Australia)

vii
Executive summary

Bringing together experts from more than 20 countries and representing 53 institutions, WHO
held the inaugural Consultative Meeting on High/Maximum Containment (Biosafety Level 4)
Laboratories Networking in Lyon, France on 13–15 December 2017. The participants
included facility operators, engineers, lead scientists and representatives of national
regulatory authorities; they identified shared challenges, opportunities for collaboration and
potential solutions to improve the design, maintenance, regulations and operations of
maximum-containment laboratories (biosecurity level 4 – BSL-4).
The participants repeatedly emphasized the importance of BSL-4 laboratories in their ability
to carry out highly specialized work during the Meeting. Public perception can significantly
influence where and how these laboratories can operate, and concerns were expressed about
how an incident in any BSL-4 laboratory would have direct implications for the reputation of
the entire community. Key factors in dispelling misconceptions about and establishing public
trust in this community included the promotion of scientific research, transparency,
highlighting of biosafety achievements and strong community liaison committees.
A global shift from prescriptive to performance-based biosafety has occurred in recent years.
To reflect these realities, the revised WHO Laboratory biosafety manual Laboratory
biosafety manual will emphasize the use of practical measures to mitigate risks, including
thorough risk assessments and evidence-based approaches to biosafety, rather than reliance
on rigid classification systems. Much discussion focused on the consequences of this shift in
approach, as many countries lacking formal regulatory requirements rely on the Laboratory
biosafety manual as their sole guidance document.
Significant attention focused on best practices in the design of high-containment facilities.
Selection of suit laboratories vs cabinet lines and planning for surge capacity through design
flexibility must be considered at an early stage. Countries with limited resources have added
restraints arising from the lack of well-trained biocontainment engineers, poor access to
relevant engineering information and difficulty in reaching effective supplier networks. The
participants, particularly those from lower-income countries, gave significant importance to
the identification of mechanisms for the global dissemination of know-how and good practice
relating to containment laboratory design. They received updates on high-containment
laboratories that were planned, newly constructed or operational, which pushed discussions to
develop a consensus on global standards or requirements for such facilities.
The need to share best practices in laboratory procedures and training programmes was a
common theme of the Meeting. Many networks of high-containment laboratories presented
their charters and activities to strengthen BSL-4 laboratories in their regions. This and other
discussion mapped numerous opportunities for training at the local, regional and international
levels, although many gaps remained to be addressed.
A final objective of the Meeting was to strengthen relations between regulators and operators,
finding common solutions to enhance biosafety while furthering scientific progress. Through
both separate breakout sessions and joint discussions, the two groups raised common

viii
concerns on issues related to laboratory safety and expressed a desire to address them
together.
The participants identified several gaps for WHO to prioritize as part of its continued
commitment to strengthening the global BSL-4 community. These included the coordination
of networks of high-containment laboratories to avoid duplication of effort, the fostering of
the development of a BSL-4 training curriculum, the dissemination of best practices and the
sharing of materials. Most important was a need to establish benchmarks and official
verification mechanisms for BSL-4 laboratories, to ensure that all such facilities operate to a
global standard of biosafety and biosecurity, building trust within the scientific community
and public alike.

ix
Introduction

BSL-4 laboratories represent the highest level of biological containment, offering

unparalleled protection for the user, sample and environment. At present, more than 50
maximum- and high-containment facilities around the globe handle some of the world’s most
hazardous pathogens to human and animal health for research and diagnostic purposes. BSL-
4 laboratories are located in all WHO regions. While most are in North America or western
Europe, a number have been built in Asia, and construction projects are underway in China,
Japan and sub-Saharan Africa, raising questions related to sustainability in low-income
countries. Irrespective of geography, all high-containment laboratories share numerous issues
regarding training opportunities, maintenance and the building of confidence in the broader
community. Many regional initiatives, but limited international efforts, have aimed to create a
global forum to identify best practices, standards and opportunities for collaboration.
The WHO Consultative Meeting on High/Maximum Containment (Biosafety Level 4)
Laboratories Networking aimed to further solutions to the challenges faced by all such
laboratories. It had eight objectives:
1. to foster bilateral or multilateral collaboration of BSL-4 laboratories around the world, to
work with WHO on the common mission of strengthening laboratories to maintain
biosafety and biosecurity;
2. to discuss best practices employed at facilities and identify mechanisms for sharing and
disseminating them to others;
3. to review challenges to consider in the development, expansion and maintenance of
facilities and identify measures used to overcome them;
4. to strengthen relations between regulators and scientists relating to oversight and identify
means to earn confidence from the global scientific community;
5. to address public perceptions of the risks associated with BSL-4 facilities and mitigate
these concerns through outreach;
6. to explore the possibility of forming an international review mechanism to provide
international recognition of new BSL-4 facilities through on site observation and
guidance;
7. to facilitate material transfer to/between laboratories that have demonstrated competence;
and
8. to update the global audience on planned and newly developed BSL-4 facilities and
discuss the support required to ensure their success and safe operation.
Annexes 1–3 to this report give the agenda of the Meeting, list BSL-4 laboratories worldwide
and list the Meeting’s participants, respectively.

Welcoming remarks by Dr Guenael Rodier, Dr Florence Fuchs and Dr Sebastien Cognat

(WHO headquarters) emphasized the importance of BSL-4 capacity in the context of the
WHO Health Emergencies Programme, where they played a central role in diagnostics and
countermeasure development against the world’s most dangerous biological agents. This
networking meeting aimed to build a community of practice and encourage participants to
1
take active roles in future world health emergencies. Most important, it provided a venue for
the BSL-4 community to express its expectations of WHO in maintaining and strengthening
joint activities to enhance biosafety and biosecurity at the global level.

Global BSL-4 laboratories – unprecedented opportunities

and unique challenges

In the keynote address, Dr Jim LeDuc (University of Texas Medical Branch, United States of
America) highlighted the specialized role played by BSL-4 laboratories in the advancement
of science and the battle against high-consequence pathogens, as well as the particular
challenges encountered in the planning, operation and upkeep of these facilities. BSL-4
laboratories provide an environment where diagnostics, research, and assessment of novel
diagnostic tests and therapeutics can be carried out on the actual target agents of disease,
rather than surrogates. They allow for characterization of newly emerging pathogens and
provide appropriate biocontainment levels for particular types of gain-of-function research.
As the field of synthetic biology moves forward, high-containment facilities may be required
to accommodate resulting new agents.
With all of their potential, maximum-containment facilities come with many associated
challenges, including extraordinary running costs. A 2017 report from the Science and
Technology Policy Institute revealed average annual operating costs of US$ 8–13 million in
the four BSL-4 laboratories in the United States of America that were surveyed. Operations
and maintenance, required for constant upkeep and rapid response to breakdowns, account for
the greatest proportion of laboratory spending. Security, utilities, staff training, animal care
and use, pathogen inactivation and waste stream management all have high associated costs
for BSL-4 laboratories. In addition to these costs, the repair of highly specialized instruments
and equipment located inside the BSL-4 space has an extra layer of complication: service
contracts are often not honoured when equipment is housed in maximum-containment zones,
leaving laboratory staff with additional training costs for inhouse maintenance.
Managing public perception through strong and positive community relationships is crucial
for laboratory success. So-called not-in-my-backyard movements can have devastating
consequences for a facility’s capacity to carry out important work. Laboratories working with
both Risk Group 4 (RG4) pathogens and live animals have extra responsibilities to dispel
myths to community members and animal rights activists. A strong community liaison
committee (CLC) – with membership from community leaders in the business, religion and
education sectors – is the best means of achieving all of this. As CLC members learn about
activities at the laboratory, they become important advocates and educate the public through
formal and informal interactions. For example, the Galveston laboratory of the University of
Texas Medical Branch has taken a proactive approach to CLC engagement, informing the
members of any incident prior to announcements from the press.
Additional challenges faced by BSL-4 laboratories include complying with numerous
national regulations (sometimes from more than one governing agency), ensuring secure yet
convenient access to and storage of pathogens, developing robust training programmes for
2
both research and engineering/maintenance staff, and devising detailed plans for safety and
accident response through close collaboration between laboratory administrators and
occupational health partners.
BSL-4 facilities should be promoted as a source of pride; they are unique resources to many
organizations and countries, and provide global benefits through safe and secure cutting-edge
responses to high-consequence pathogens. The BSL-4 community as a whole must work to
enhance its public image, publicize its excellent track record for safety and security, and
realize that any newsworthy incident in any facility, positive or negative, will have direct
influence on all facilities in the global BSL-4 enterprise.

Update on the revision of WHO’s Laboratory biosafety

manual

Dr Kazunobu Kojima (WHO headquarters), focal point for biosafety and laboratory
biosecurity, described the progress made in revising the 2004 edition of the WHO Laboratory
biosafety manual.1 The new edition will feature a significant change from a prescriptive to an
evidence- and risk-based approach. The manual will also have a new format: a concise
central core accompanied by annexes published as monographs on specific topics.
The WHO biosafety audience varies. While many scientists and biosafety practitioners come
from highly specialized facilities, others come from very different realities. For some, even in
national infectious disease hospitals, access to personal protective equipment (PPE) and
regular certification and maintenance of critical equipment are luxuries with limited
availability. The concept of a BSL also varies greatly by location and even within countries.
Some BSL-3 laboratories, for example, are very similar to BSL-4 laboratories, while others
resemble BSL-2 or are modular BSL-3 with varying designs. For maximum-containment
facilities, average annual operational costs upwards of 10% of total construction costs
demonstrate challenges in sustainability for many who consult the Laboratory biosafety
manual for guidance. During outbreaks, even Ebola virus has been safely manipulated in a
makeshift glove box in a field laboratory setting, without a positive pressure suit.
Rather than equating RGs with BSLs, both the pathogens (hazards) and associated processes
(likelihood) should dictate appropriate containment measures. Risk does not arise from the
pathogen alone, but results from the process, each having its own likelihood of generating
harm with varying degrees of severity. Procedures involving animal inoculations and aerosol
generation come with higher inherent risks than running enzyme-linked immunosorbent
assays (ELISAs) and preparing serial dilutions.
The new edition of the Laboratory biosafety manual would therefore focus on practicality,
taking a more evidence- and risk-based approach to biosafety to enhance flexibility. The new
manual’s three key elements would be: a renewed focus on good microbiological practices,

1
Laboratory biosafety manual, third edition. Geneva: World Health Organization; 2004
(http://www.who.int/csr/resources/publications/biosafety/WHO_CDS_CSR_LYO_2004_11/en, accessed 14
November 2018).
3
emphasis on staff competence and training, and highlighting of the importance of proper risk
assessments. Specifically, the manual intended to remove the focus on risk groups and BSL at
the global level to allow for appropriate and practical measures to mitigate risks. Instead, risk
assessments must determine core requirements, referring to a combination of elements to
implement as minimum requirements for working with any given pathogen.
As assessed risk increases owing to processes, additional safety measures must be in place.
Maximum containment might be required with eradicated diseases such as smallpox, known
agents of high consequence or unknown agents and procedures with a high likelihood of
exposure and impact on the environment if released.
Ultimately, the Laboratory biosafety manual was not intended to replace or compete with
national regulatory frameworks, which would dictate how to deal with benign versus high-
consequence agents. Instead, the preference was to be risk/performance based and for
ultimate decisions to come from each government. Countries such as the United States, which
relied on Biosafety in microbiological and biomedical laboratories (BMBL)2 for biosafety
guidance, were not expected to abandon their national regulations. Instead, the Laboratory
biosafety manual would be important for the resource-limited audience.

Varying approaches to high-containment facilities

Dr Kathrin Summermatter (Institute of Virology and Immunology, Switzerland) described

varying approaches to high-containment facilities, highlighting the absence of a one-size-fits-
all solution. The Institute of Virology and Immunology decided to upgrade an existing
facility, rather than undertake a new construction project. Project planning discussions with
architects raised many questions that are common to the global BSL-4 community and
warrant discussion for shaping future facilities.
Containment laboratory terminology is not universal, with interchangeable terms used by
different countries, regions and international organizations. These include containment level
4 (used in the European Union (EU) and Canada), BSL-4 and animal biosafety level 4
(ABSL-4) (United States, WHO), and Physical Containment Level 4 (PC4) (Australia).
Practices within different maximum-containment facilities also vary, with human pathogen
BSL-4 laboratories consisting of suit laboratories or glove boxes while Containment Level 4
Agriculture (CL4 Ag) (BSL 3 agriculture – BSL3Ag) lack such special protection for
workers. Beyond the facility level, classification schemes for biological material also vary by
region, field (human versus veterinary) and endemicity. In dealing with globally eradicated
agents, specific regulatory control and higher containment levels may be required out of fear
of reintroduction, as with rinderpest and smallpox. While classification schemes may be
useful at the national level, they may therefore not be applicable internationally.

2
Biosafety in microbiological and biomedical laboratories (BMBL), 5th edition. Atlanta: US Department of
Health and Human Services; 2009 (https://www.cdc.gov/biosafety/publications/bmbl5/index.htm, accessed 18
November 2018).
4
Moving from this traditional approach, the selection of appropriate containment levels and
controls should focus on risk-based approaches, taking account of the activities and
procedures to be carried out. According to BMBL, hantavirus, for example, can be safely
handled in BSL-2 facilities with BSL-3 practices for diagnostic purposes. If the same agent
will be used for chronic infection studies in rodents, however, then ABSL-4 is required.
Giving careful consideration to realistic needs is especially important, given the high
associated costs and issues of sustainability with high-containment facilities. This becomes
even more critical with the tendency to gravitate towards new to market containment
technologies whose added benefits are yet to be proved.
On a simplified level, all forms of maximum-containment laboratories have many
commonalities. Design features include air handling units, breathing air systems for suit
laboratories, supply and exhaust high-efficiency particulate air (HEPA) filters, material
transport docks (dunk tanks, pass-through chamber, autoclaves), shower barriers, effluent
treatment systems and built-in redundancy for critical systems. Areas of debate include the
precise placement of HEPA filters, the specific type to use and the installation of fixtures
entirely within or outside the containment zone.
In large-animal facilities, the room itself becomes the primary containment barrier, putting
greater requirements on the whole building. Building flexibility into the facility is highly
desirable to enable unexpected needs during outbreaks of emerging and re-emerging
infectious disease to be met.
While establishing a standard definition for BSL-4 laboratories may be difficult, exchanging
information on how best to integrate safe systems will assist the building of new facilities that
are sustainable and allow the scientific programme to continue. Whether new technologies
and engineering requirements are beneficial or burdens to laboratory operations and
sustainability, and how best to integrate experiences and lessons learned into new projects
were additional areas to address.

Update on BSL-4 facilities

Planned high-containment laboratories

Nagasaki University, Japan

In 2010, the President of Nagasaki University publicly announced that the possibility of BSL-
4 construction was being explored. Since 2011, the University had actively engaged with
community members to educate the public and establish trust prior to the start of
construction. These activities included over 50 briefing sessions for neighbourhood residents,
12 community meetings since 2016 and 38 science seminars open to the public. By 2016, the
Government had provided official support and set aside money in the 2017 national budget.
The planned facility would be five storeys high, with 1000 m2 divided between two
independently operated BSL-4 units, each with a laboratory and animal room. While
Nagasaki does not sit on active earthquake fault lines, seismic isolation layers for building

5
construction on a vertical isolation device were being planned as an extra precaution. The
proposed timeline consisted of construction in 2018–2019, commissioning in 2020 and
commencement of operations by 2021.

Chinese Center for Disease Control and Prevention BSL-4 Laboratory, China
The Chinese Center for Disease Control and Prevention (China CDC) was established in
Beijing in 2002, housed numerous WHO reference laboratories and collaborating centres on
viral and vector-borne diseases, and had the largest BSL-3 facility in China, yet lacked a
maximum-containment facility. Given China’s enormous population and increasing pressure
from infectious diseases as the economy shifted, China CDC recognized the need for and
obtained government funding to construct a BSL-4 facility.
The China CDC BSL-4 would be a suit laboratory, designed in accordance with Chinese and
international standards (including the WHO Laboratory biosafety manual), with activities
including diagnostics, the evaluation of new kits and vaccines, and research into
pathogenicity and animal models. Thus, the facility would include both a laboratory and an
animal suite capable of housing nonhuman primates, pigs, rabbits and rodents. The project
was at the very beginning of planning and a suitable construction site had yet to be
determined.

Public Health England, United Kingdom

Public Health England planned a world-class, £400-million new construction project,
relocating staff and facilities from Porton Down and London. In 2017, it purchased a vacant
site in Harlow, and the Harlow district council approved construction plans in December.
The new facility at Harlow would house a number of laboratories, particularly the first BSL-4
suit laboratory in the United Kingdom, which had previously permitted only cabinet lines for
work with RG4 pathogens. To obtain approval, a tripartite working group was established to
address multiple regulatory issues surrounding a suit laboratory. A great deal of work
remained in the planning stages, from addressing issues relating to the chemical shower,
selection of disinfectants and technologies for room decontamination, communications and
ergonomics, ways to continue business as usual in this transition phase, handling of health
surveillance questions, mock-ups for training and external suit training opportunities for staff.
The Harlow facility was hoped to be operational by 2024, with construction work beginning
in 2019 and retrofitting of an existing building for BSL-3 starting in 2021.

High-containment laboratories under construction

Research Centre for Emerging Pathogens with High Infectious Risk, Pasteur
Institute Côte d’Ivoire
The Pasteur Institute currently operated two facilities in Abidjan, Côte d'Ivoire, housing
recently constructed BSL-2 laboratory space for virology work, the biobank and the
molecular biology unit. The need for a BSL-4 facility in the region was identified following
recent outbreaks of dengue fever in Côte d’Ivoire and Ebola virus disease in neighbouring

6
countries. A call for funding was made in 2015 to construct a new laboratory, the Research
Centre for Emerging Pathogens with High Infectious Risk (CEPRIS), to include a BSL-4 suit
laboratory and a BSL-3 laboratory, plus an animal suite and insectarium at BSL-3. Built-in
flexibility would come from the ability to convert the BSL-4 facility to BSL-3 as required by
the work volume. The scientific programme of CEPRIS would take a One Health approach,
focusing on pathogens of human, animal and environmental origin. Planned activities
included surveillance and diagnosis, research and characterization of pathogens; biobanking;
and hosting and training of local and international teams.
Côte d’Ivoire’s national budget provided about 90% of the funding required, and the
remaining 10% came from international organizations such as WHO; the Centers for Disease
Control and Prevention (CDC), United States of America; and the Pasteur Institute, Paris,
France. Construction began in 2016, after consultation and planning with architects and
industrial partners, and establishing compliance with national and international laws and
conventions on such issues as ethics, biosecurity and privacy. Many partners at the national
level (the ministries of health and defence) and the international level (CDC, WHO and the
Jean Mérieux BSL-4 laboratory, in Lyon, France) also played significant roles in project
planning and implementation. The project was predicted to be completed in 2019.

National Bio and Agro-Defense Facility, United States of America

The National Bio and Agro-Defense Facility,a state-of-the-art BSL-3 and -4 facility, was
being constructed in Manhattan, Kansas, following a presidential directive in 2003 to replace
the Plum Island laboratory. The facility was a joint project of the US Department of
Homeland Security, the US Department of Agriculture and the Agricultural Research Service
and Foreign Animal Disease Research and Diagnostic programmes, and would thus offer a
One Health approach to detect, diagnose and develop countermeasures against high-priority
foreign animal disease.
The phase of facility design ran from 2007 to 2012. Site preparation started in 2010 and was
completed in August 2012, and construction began in 2015. About 45% of the budget of
US$ 1.25 billion had been spent. The main laboratory building would offer 174 955 m2 of
laboratory space, largely occupied by a BSL-3 laboratory and large-animal areas, as well as
BSL-2 and biologicals development module for in-house vaccine manufacturing. The BSL-4
suite would cover about 4 084 m2, and be the first BSL-4 facility in the United States to
accommodate large animals. The building design would also allow for flexibility, where the
large-animal BSL-4 suite can be operated at BSL-3Ag. If progress continued on schedule,
NBAF would be commissioned by May 2021.

Facilities at the Pirbright Institute, United Kingdom

The Pirbright Institute is an international centre of excellence for livestock pathogens of
economic significance, as well as exotic zoonotic agents. For nearly nine years the United
Kingdom Government and the Biotechnology and Biological Sciences Research Council
(BBSRC) had made major investments to replace aging facilities, some being up to 100 years
old. The BBSRC National Centre for Virology was constructed entirely to BSL-4 standards
to allow for diagnostic activity and in vitro research with RG3 and 4 animal pathogens
7
(Specified Animal Pathogens Order level 4 – SAPO4) and Advisory Committee on
Dangerous Pathogens level 3 (ACDP3) according to the United Kingdom’s human and
animal health classification scheme), as well as zoonotic agents (ACDP4). The Plowright
Building cost £135 million, had been occupied since 2015 and employed entirely cabinet
lines for work with ACDP4 pathogens. An additional facility, the BBSRC National Centre
for Vaccinology (the Jenner Building) had been operational for about a year.
Several additional construction projects were planned or underway at Pirbright. A new
hatching facility for specific pathogen free (SPF) poultry had been designed and was
expected to be operational by 2019. Updates to current animal facilities would create a
poultry experimental facility, with open pens capable of ACDP3 animal work with isolators,
that was expected to be operational by 2019. Finally, a new SAPO4/ACDP3 (BSL-3Ag+)
large-animal facility had been designed and the contractor selected, and operations were set
to begin by February 2021. This high-containment facility would be built to BSL-4 standards,
with the potential to add air lines for a future suit laboratory.

National High Containment Facilities for Animal Diseases Control and

Prevention, Harbin, China
The Harbin Veterinary Research Institute houses numerous facilities for research and
diagnostics of animal diseases. The campus includes a veterinary school, veterinary
biotechnology development company, a BSL-1/2 facility with 8000 m2 of laboratory space, a
BSL2/3Ag facility of 17 000 m2, and a facility with capabilities for housing small animals in
isolators and large animals in modular open pens. There are also facilities for breeding SPF
pigs, ducks and chickens.
China has the largest population in the world, hosts hundreds of millions of tourists each year
and has become the largest and fastest-growing import market. It is also home to over 20% of
the world’s poultry and 50% of the world’s pigs, and has a fast-growing cattle industry.
These facts, combined with China’s limited natural resources, created major biosecurity
concerns about the accelerated replication, mutation and transmission of infectious
pathogens. As a result of the 2003 outbreak of severe acute respiratory syndrome (SARS), the
Chinese Government planned to build three BSL-4 facilities to address these issues.
The National High Containment Facilities for Animal Diseases Control and Prevention,
constructed at the Harbin Veterinary Research Institute, would be China’s only facility
capable of large-animal BSL-4 studies. Nearly 4500 m2 were dedicated to high-containment
laboratories, including four BSL-3 spaces, four ABSL-3 rooms, one necropsy room, four
BSL-4 laboratories and four ABSL-4 suites. Construction was completed in December 2016
and the facility obtained accreditation for work with pathogens in RG3 from the China
National Accreditation Service for Conformity Assessment. By the end of 2017, the facility
was hoped to have accreditation for RG4 pathogens, and work on these was hoped to start in
2018.

8
Recently constructed BSL-4 laboratories that are operational

National High-level Biosafety Laboratory, China

The National High-level Biosafety Laboratory, in Wuhan, represents one of China’s major
investments in strengthening the public health system and biosafety management following
the SARS outbreak. The building features 3000 m2 of BSL-4 space, including four
independent laboratories areas and two animal suites, in addition to 20 BSL-2 and two BSL-3
laboratories. The Laboratory’s main objective is to work for the prevention and control of
emerging infectious diseases through diagnostic activities, as well as research and
development in the areas of pathogenesis studies and antiviral drugs/vaccines.
The Laboratory is the result of a 2004 memorandum of understanding between China and
France, which collaboratively engaged in the design and commissioning of the project. Both
French and Chinese companies validated the Laboratory, which was fully accredited by both
countries as of December 2016 and certified to International Organization for Standardization
(ISO) standards.
During the commissioning process, much investment was made in staff training. Researchers
were trained in Australia, Canada, France and the United States of America and then in house
before the Laboratory became operational. A validation system for training was then
established to demonstrate staff competency for work or maintenance in the BSL-4
laboratory, establishing management systems and drafting of guidelines and standard
operating procedures (SOPs). The BSL-4 laboratory could carry out projects on many
diseases, would work as a national centre for research and development and aimed to become
a WHO reference laboratory or collaborating centre.
The BSL-4 laboratory was not currently operating at full capacity, as animal experimentation
would commence only after significant hands-on experience with in vitro work, owing to
increased risk. The Laboratory was intended to be a transparent public platform for China.

Korea Centers for Disease Control and Prevention BSL-4 Laboratory, Republic
of Korea
The Korea Centers for Disease Control and Prevention (KCDC) BSL-4 laboratory, located in
Cheongju, was established to respond rapidly to public health emergencies through the
diagnosis of high-risk pathogens and development of vaccines and drugs against emerging
infectious diseases.
The construction project for the Laboratory was launched in 2009, with design completed in
2012 and construction in 2014. Biosecurity was a major consideration in all stages of the
project, from the geographic location selected to facility access. By June 2016, the
Laboratory had been accredited and begun operation. The facility housed BSL-2 and -3
laboratories, as well as 300 m2 of BSL-4 laboratory space.
The Division of Bioterrorism Preparedness and Response operated the BSL-4 laboratory,
which had undertaken immense work in the area of biological risk management, the
development and continuous revision of SOPs and the establishment of emergency response

9
drills to ensure safe operation of the facility. Facility staff attended international training
courses in collaboration with the Public Health Agency of Sweden, the University of Texas
Medical Branch and CDC. A rigorous internal programme was established that provided
BSL-4 training to researchers, operations staff and maintenance personnel; this included task-
specific theoretical, practical and mentoring components prior to certification.

Victorian Infectious Diseases Reference Laboratory, Australia

The Victorian Infectious Diseases Reference Laboratory (VIDRL) is part of the Royal
Melbourne Hospital and housed at the Doherty Institute. It is a national public health
laboratory with diagnostic functions, performing about 300 000 serological, molecular and
microbiological tests per year. VIDRL houses many national reference laboratories and WHO
collaborating centres and is home to over 700 scientists, educators, clinicians and students.
In 2014, the National High Security Quarantine Laboratory at VIRDL was commissioned as a
high-containment diagnostic laboratory to detect imported viral haemorrhagic fevers, as well
as diagnose smallpox and other high-threat pox viruses.
The BSL-4 laboratory at VIRDL is a single suite of about 90 m3 located in a high-
containment facility with seven BSL-3 laboratories. Particular design features include an off-
the-shelf chemical shower, built-in vaporized hydrogen peroxide (VHP)/gas decontamination
pipework, a pass-in chamber and a dunk tank. Ultimately a decision was made to switch from
VHP to the more gas-like ionized hydrogen peroxide, so the laboratory uses a stand-alone
unit for decontamination and the VHP piping remains unused. In addition, the laboratory was
designed with an adjacent control room with a large window. This room is constantly staffed
whenever BSL-4 laboratory work is carried out, with the controller acting as a biosafety
practitioner, as well as record keeper and note taker for the laboratorian. During the Ebola
virus crisis of 2014–2016, the laboratory was activated 33 times for diagnostics on suspect
cases. In the absence of diagnostic work, the laboratory is involved in assay development,
testing, antiviral drug screening; it is open to future collaboration.

BSL-4 laboratory at the Robert Koch Institute, Germany

The Robert Koch Institute, in Berlin, is a federal institute under the Federal Ministry of
Health, working to safeguard public health in Germany. The final designs for its BSL-4
laboratory were approved in 2006, with construction taking place in 2010–2015. German
legislation requires all authorizations and permissions to come from state or federal
regulators. This resulted in the laboratory approaching multiple authorities for permissions in
accordance with the Genetic Engineering Act, Biological Agents Ordinance, Animal Welfare
Act and Protection against Infection Act. As of July 2017, the laboratory satisfied all external
review committees and authorities for compliance with nearly 140 regulations, and obtained
licences to work with mice, guinea pigs and hamsters.
The 330-m² BSL-4 facility is subdivided into two suites that can operate independently, each
with a laboratory space, animal room and necropsy room. In total, the laboratory contains
eight Class II biosafety cabinets and can accommodate up to 10 operators at a time. All
processes were validated, including the chemical shower via use of fluorescent material to

10
show coverage of entire suite, and the necropsy room autoclave by embedding spores in
carcases prior to runs. The BSL-4 laboratory was running in a mock phase, using BSL-2
agents, and expected to begin work with RG4 pathogens in March 2018.

Established high-containment laboratories – moving to the future

Australian Animal Health Laboratory, Australia

The Australian Animal Health Laboratory (AAHL), operated in Geelong under the
Commonwealth Scientific and Industrial Research Organisation, had been operational since
1985 and played a vital part in the Australian biosecurity infrastructure. It was designed to
carry out research and diagnostic activities to protect Australia’s livestock and general public
from emergency and zoonotic disease threats, with approximately 400 m2 of BSL-4
laboratory space plus 127 m2 of BSL-4 animal suites. AAHL’s uniqueness lies in its ability to
conduct high-containment research at all levels, from in vitro through insects to large
animals. While the building was designed for a 100-year lifespan, changing research demands
and technologies made this goal unrealistic. The cost of construction was approximately
A$ 185 million in 1985, whereas the current cost to rebuild would be over A$1 billion. As the
annual budget was A$ 63 million, a new construction project was unlikely.
AAHL was designed with a modular concept, and contained numerous suites. It also
contained a large training laboratory that provided critical training for staff involved with
large-animal work, providing technical training while suited prior to working with RG4
agents. Major refurbishing projects in recent years had greatly added to AAHL’s capacity for
BSL-4 research: BSL-3 spaces were upgraded to BSL-4. A 350-m2 BSL-4 zoonosis suite had
recently been added that contained laboratory space and insectary, two small-animal rooms,
and a bioimaging facility. A BSL-3 insectary had also been built, with space for rearing and
feeding insects, as well as animal accommodation for transmission studies. A new, extensive
expansion project being planned and funding negotiations were underway.

US Army Medical Research Institute of Infectious Diseases, United States of

America
The US Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort
Detrick, in Frederick, Maryland, is arguably the oldest high-containment facility. Its mission
is to provide leading-edge medical capabilities to deter and defend against biothreats, and its
vision is to be a leader in advancing medical biodefence to protect US military forces and the
nation. Its core competencies are to prepare for uncertainty and emerging infectious diseases,
achieved through:
1. developing, testing and evaluating medical countermeasures;
2. providing world-class expertise in medical biological defence;
3. rapidly identifying biological agents;
4. training and educating the force;
5. maintaining biosafety, biosecurity and biosecurity standards; and
6. preparing for technological uncertainty.

11
Through these competencies and with the efforts of subject matter experts from a variety of
fields, USAMRIID fulfils its vision. Using appropriately developed animal models, it
generates data on medical countermeasures of such quality that they can go directly to the US
Food and Drug Administration for licencing when human clinical trials are not possible.
Vaccines and countermeasures had been developed at USAMRIID targeting a range of
biological threats, including anthrax, plague, hanta- and filoviruses, ricin toxin and
Staphylococcal enterotoxin B.
USAMRIID planned to move from its current facility to a newly constructed site in the
coming years. The new building would be the largest, most complex biocontainment facility
ever designed, nearing 304 800 m2. Scientific capacity was expected to be 4–5 times as large,
and new capabilities for BSL-4 studies would include positron emission tomography (PET),
computed tomography (CT), and magnetic resonance imaging (MRI) and structural biology.

New laboratories and public opinion: earning public trust

and support

The many challenges and lessons learned in earning public support, and the link between
public perception and concerns and mistrust were discussed, using the examples of
laboratories in the United States and Japan.

National Emerging Infectious Diseases Laboratories, United States

of America
The mission of the National Emerging Infectious Diseases Laboratories (NEIDL), in Boston,
is to conduct research on infectious disease for the local, national and global good. Messaging
around this and other national biocontainment laboratories included a mission to develop
countermeasures against bioterrorism agents, which often overshadowed the real public
health concerns surrounding emerging and re-emerging infectious diseases. While initial
local press releases seemed quite favourable, messaging on NEIDL gradually became more
negative, and the use of terms such as bioterror lab and bioweapons lab increased public
mistrust.
NEIDL is in a populated area, near Boston University Medical Campus and many residences,
ranging from low-income public housing to multimillion-dollar condominiums. Despite the
diverse income levels, the public’s underlying assumption was that NEIDL’s site had been
selected because many poor people lived in that area. Specific concerns raised in Boston were
that BSL-4 laboratories pose unacceptable public risk, that secret work on bioweapons would
be done and that there were more than enough other BSL-4 laboratories to handle the existing
scientific problems. Movies, books and even news releases gave sensational accounts of the
public’s exposure to high-consequence pathogens, and there was a misperception that any
breach in containment would result in a major pathogen release. Incidents in any high-
containment laboratory further add to public unease about any nearby facilities.

12
The city of Boston had a long history of community activism by neighbourhoods and of
questioning government and other authorities. Federal and state lawsuits filed against the
National Institutes of Health and the State of Massachusetts in 2005 and 2006 stated that risk
assessments for NEIDL had failed to address worst-case scenarios. A supplemental risk
assessment was requested and undertaken shortly afterwards. It required nearly four years to
complete, considered 13 pathogens and 300 failure scenarios, and addressed environmental
justice issues. Once the lawsuits were favourably resolved in 2014, NEIDL began actively
inviting members of the public for tours and conversation inside the facility. These events
allow personnel to provide information addressing their specific concerns. As a result, almost
3000 people had visited NEIDL; in addition, scientific staff regularly attended public
meetings and participated in other outreach activities, and the community liaison committee
was active.
Many lessons were learned on the path to gaining acceptance for NEIDL in Boston. In
particular, the personnel were not fully prepared to communicate effectively with the public
about either science or risk. As misperceptions are difficult to predict, they must be drawn out
of people in order to be addressed. People’s beliefs and individual histories influence how
well they listen and what they truly hear.
No laboratory can promise that no incident will ever occur. If/When one does happen,
however, communicating about it and using the opportunity to teach the public about
redundancies and maintaining safety are critical. Scientists and safety professionals need to
engage more actively in communicating why their work is important and how safe and secure
science is carried out, and helping to distinguish minor from serious incidents.

National Institute of Infectious Diseases Laboratory, Japan

The National Institute of Infectious Diseases Laboratory, in Tokyo, constructed a laboratory
was in 1981 with a cabinet line for BSL-4 capabilities. It had been used only as a BSL-3
laboratory since that time, however, owing to the lack of approval from the Ministry of
Health, Labour and Welfare, compounded by lack of mutual understanding between the
Laboratory and the local government.
The Laboratory’s responsibilities included preparing against viral haemorrhagic fevers and
the threat of bioterrorism associated with these fevers and smallpox, preparing for emerging
virus infections such as SARS and Middle East respiratory syndrome-related coronavirus,
and training scientists to develop surge capacity to work with diagnostic specimens
containing highly pathogenic agents in the event of an outbreak. The Laboratory was also
involved in many research projects, including the development of diagnostic systems and
vaccines for viral haemorrhagic fevers and other emerging viruses, studies on virus therapies
for monkeypox and severe fever with thrombocytopenia syndrome, and studies of the
efficacy of a highly attenuated smallpox vaccine in a nonhuman primate model.
In 2015, the National Institute of Infectious Diseases Laboratory finally received approval to
use the gloveboxes for work with RG4 agents. It pursued a long process to promote mutual
understanding with local communities and understanding of BSL-4 work. Activities to
engage the public included open houses, inviting local community members to tour the BSL-
13
4 laboratory, and regular meetings of the communication committee with local residents,
local municipal government, the Ministry of Health, Labour and Welfare and medical
experts. Transparency was essential in obtaining support and trust from the public, and the
National Institute of Infectious Diseases Laboratory was committed to playing a role in
controlling, combating and managing infections associated with highly pathogenic agents in
Japan and abroad.

Activities of other organizations and high-containment

laboratory networks

World Organisation for Animal Health

The World Organisation for Animal Health (OIE), located in Paris, France, is an
intergovernmental organization aiming to deliver timely, high-quality information and
services to allow the management of risks to the health and welfare of terrestrial and aquatic
animals, minimize associated dangers to human health and economy, and protect the
environment and biodiversity, using a One Health approach. Founded in 1924 in response to
rinderpest, OIE currently had 181 Members (countries), 12 regional and subregional
representatives, 73 partner organizations, 267 reference laboratories with expertise on
designated pathogens or diseases, and 55 collaborating centres with expertise on specialty
knowledge areas, such as biosafety.
OIE’s major responsibility is to ensure transparency of the global situation of animal disease
through gathering and sharing information. When Members notify OIE of important disease
events, it makes official reports and disseminates them to national delegates and the public
via the World Animal Health Information Database. Members have an obligation to report on
over 100 OIE-listed diseases, as well as emerging diseases and significant epidemiological
events.
In addition, OIE aims to improve veterinary services by preventing and controlling the spread
of important animal diseases, setting international standards, and sharing data and core
competencies. OIE’s science-based standards, including the terrestrial animal health code3
and the manual of diagnostic tests and vaccines for terrestrial animals,4 include specific
sections related to biosafety. As outlined in Chapter 1.1.4 of the manual, “individual
biosafety and laboratory biosecurity measure or composite measures, rather than a designated
biosafety level … guides a laboratory in the safe and secure handling of any individual
biological agent or toxin”. While OIE does not have a particular BSL-4 focus group, it is a
standard-setting organization, an information hub and a very valuable network with reference
centres in 38 countries.

3
Terrestrial animal health code 2018. Paris: World Organization for Animal Health; 2018.
4
Manual of diagnostic tests and vaccines for terrestrial animals 2018, Vol. I and II, eighth edition. Paris: World
Organization for Animal Health; 2018.
14
International Experts Group of Biosafety and Biosecurity
Regulators
The International Experts Group of Biosafety and Biosecurity Regulators (IEGBBR) is an
informal group of biosafety and biosecurity regulators from 11 different countries, as well as
observers from WHO and OIE. Its mission is:
1. to provide a forum for the sharing of knowledge and experience with issues related to the
oversight of human and animal pathogen biosafety and biosecurity;
2. to promote international cooperation among competent regulatory authorities to
strengthen and advance global regulatory mechanisms for the oversight of biosafety and
biosecurity; and
3. to support more global or mutually complementary responses to emerging issues and
threats posed by human and animal pathogens.
All members have oversight functions in their countries on biosafety biosecurity or both.
New memberships are discussed with a steering committee (comprising a chair, co-chair and
member) and there are no restrictions on the geographical location of members.
IEGBBR meets on a biannual basis, with its first meeting in Canada in 2007. Topics
discussed include updates in member countries on issues such as regulatory revisions, dual
use, and the regulation of technologies (clustered regularly interspaced short palindromic
repeats (CRISPR), synthetic biogy), incidents and inspection regimes . Current activities
included constructing a website, preparing a compendium of regulation and oversight of
biosafety and biosecurity in different countries, sharing information on the oversight of dual-
use research and outreach to the European Commission on the revision of directives and to
WHO on poliovirus containment.
In addition, IEGBBR is willing to provide expertise to international groups and organizations
– from the International Genetically Engineered Machine Competition Foundation to ISO and
the Global Partnership against the Spread of Weapons and Materials of Mass Destruction – to
promote the building of capacity for global biosafety and biosecurity.

Biosafety Level 4 Zoonotic Laboratory Network

The Biosafety Level 4 Zoonotic Laboratory Network (BSL4ZNET) was established in March
2016 to strengthen international coordination, improve knowledge sharing and leverage
partnering capacity to respond to current and emerging high-consequence zoonotic biothreats
through partnerships between animal health and public health laboratories. It emphasizes the
word zoonotic, as the initiative stemmed from the Canadian Food Inspection Agency,
national regulators of food safety and animal health.
BSL4ZNET consists of 12 member organizations from five countries: Australia, Germany,
Canada, the United States and the United Kingdom. Activities centred on four main strategic
focus areas, each with its own working group: knowledge sharing and institutional
cooperation, international response and surge capacity, scientific excellence and training.

15
After its inception, BSL4ZNET established direct and efficient communication lines between
BSL-4 professionals in 60 active members, with over 100 documents shared and hundreds of
participant hours invested in working groups’ teleconferences. Key outcomes achieved
through BSL4ZNET included creating partnerships and sharing best practices between
international animal and public health laboratories, facilitating international staff exchanges
and a process map for material transfer and exchange between network partners, addressing
critical gaps in research knowledge via the DISCONTOOLS database and building capacity
for BSL-4 laboratories through a systematic evaluation of positive pressure suits.
BSL4ZNET planned to continue building capacity through a workshop on high-containment
necropsy, develop broader partnerships to address critical research gaps and develop effective
countermeasures, and transfer knowledge and technology globally to areas of particular need.

Group of High Containment Laboratories Directors

The Group of High Containment Laboratories Directors (GOHLD) provides an informal
trusted environment in which laboratory directors can meet and openly discuss operational
and management issues in their high-containment laboratories working with animal
pathogens and/or high-threat zoonotic agents. The Group’s members provide mutual support,
facilitate the sharing of best practices for biological risk management and have the
opportunity to harmonize top-level procedures. Further, the Group enables facility directors
from around the globe to provide a united response on issues related to high-containment
laboratories to, for example, WHO and OIE. In 2016, the Group published Guidelines for
Livestock Biosafety Manual Development, which covered topics ranging from general
directives on biological safety to special safety arrangements, stretching from PPE to risk
management and laboratory inspections. Further direct benefits included collaboration
between members during laboratory commissioning, decommissioning and demolition
projects with the Pirbright Institute, United Kingdom and the US Department of Agriculture.
In addition to its role as forum for directors, the Group promotes cooperation in the area of
applied research on laboratory biosafety and biosecurity and facilitates national and
international training in biocontainment, biological risk management, biosafety and
laboratory biosecurity. It also cooperates with external groups in facilitating access to BSL-3
animal facilities across Europe, should an outbreak of animal or zoonotic disease occur.

Efficient response to highly dangerous and emerging pathogens at

EU level
Efficient response to highly dangerous and emerging pathogens at EU level (EMERGE) is an
EU-funded joint action with 38 partner institutes from 25 countries, created to address the
need for an efficient, rapid and coordinated response to high-threat pathogens causing serious
cross-border outbreaks. Coordinated by the Robert Koch Institute and with funding for 2015–
2018, EMERGE contains seven work packages and stems from previous joint actions that
linked existing EU-funded networks on highly infectious bacteria and viruses with a
European BSL-4 network.

16
EMERGE has three main objectives: to ensure efficient responses to emerging and re-
emerging cross-border events, to ensure coordinated and effective responses to such
outbreaks by linking up laboratory networks and institutions, and to perform external quality
assurance exercises and provide appropriate training that ensure laboratory preparedness to
perform diagnostics and manage biological risks in case of an outbreak. Annual assessments
are carried out to determine the priority agents, viruses and bacteria in RG3 and RG4 that
have the greatest cross-border potential. If gaps in diagnostic capabilities are not addressed
and no other networks are engaged in such activities, the agent is prioritized under the joint
action.
In line with its objectives, EMERGE has two operational modes. For the interepidemic mode,
priorities include the development of protocols and guidelines, and the assessment and
enhancement of laboratory performance. For the outbreak response mode, dedicated funding
is released to support network interoperability, the development of recommendations for
diagnostic approaches, quality assurance for diagnostics, the provision of ad hoc training, and
the validation and improvement of biological risk management. The switch from one mode to
the other follows initial input from international organizations such as OIE and WHO,
followed by evaluation by the EMERGE steering committee.

European Research Infrastructure on Highly Pathogenic Agents

The European Research Infrastructure on Highly Pathogenic Agents (ERINHA) is an EU
research infrastructure dedicated to RG4 pathogens and the study of emerging highly
infectious microorganisms. It is a distributed research infrastructure that links members and
external users, including scientists from academe and industry, with European BSL-4
laboratories and complementary facilities, to allow for high-calibre research and development
projects and services that could not be provided by a single national infrastructure or BSL-4
network. ERINHA was initiated before 2008 and entered its formal preparatory phase in
2010. As of July 2017, it was recognized as an international non-profit-making association
under Belgian law and had a central administrative hub in Paris. It was planned to become
operational in 2018. ERINHA would have a general assembly (decision-making body),
executive board (executive body and source of proposals) and a director-general.
ERINHA’s research portfolio particularly prioritized RG4 pathogens based on the WHO
Research and Development (R&D) Blueprint. Its internal research agenda focused on
increasing its capabilities, expertise and competitiveness, while its external research agenda
addressed external collaboration, project hosting and research contracts.
The central coordination unit would be the access point for any requests to use ERINHA. It
would perform scientific management, and provide access to services, advice and project
coordination.
Current ERINHA activities included finalizing operational frameworks and recruiting the
central coordination unit. Proposals for new scientific programmes (internal and external)
were being developed; new European members countries were being recruited and
international collaboration was being established. In addition, ERINHA advocated on the EU

17
and international levels to keep research on highly infectious diseases a high priority on
funding agendas.

Unique opportunities to advance global health enabled by

high-containment facilities

Next the participants discussed the unique opportunities offered by BSL-4 facilities to
advance health, using the examples of facilities in the United States, India and Spain. BSL-4
laboratories are expensive to run and difficult to construct and bring online, and require
tremendous investment for maintenance, but the need for such facilities cannot be
understated. While some studies can be performed in the field, others really require a BSL-4
facility. Similarly, studies utilizing surrogates do not necessarily provide data that are fully
applicable for the agent in question. BSL-4 laboratories provide added benefits at a global
level, where the highly trained biocontainment workforce can be deployed in emergency
outbreaks and provide expertise based on experience with diagnostics, packaging of samples
for shipping, and correct PPE usage for people at risk. Further, deployments may evolve into
partnering opportunities, in which where laboratorians and clinicians from areas receiving
outside assistance obtain training in biocontainment not only during outbreaks but also in-
house at host high-containment facilities.
BSL-4 laboratories offer additional benefits, including the isolation and characterization of
unknowns, testing of novel inactivation products and procedures, and modifications of assay
parameters as new discoveries are made. For example, the Ebola-virus-specific ELISA was
originally developed for use with whole blood and later modified for testing of semen
samples. In addition, animal models are being developed to mimic the persistent infections
observed in the most recent Ebola virus outbreak.

Integrated Research Facility, National Institute for Allergy and

Infectious Diseases , United States of America
Construction of the Integrated Research Facility (IRF) of the National Institute for Allergy
and Infectious Diseases, which is located at Fort Detrick and houses two BSL-4 laboratories,
began in 2005; it began operations in 2012 and obtained CDC select agent approval in 2014.
IRF’s mission is to manage, coordinate and facilitate research on emerging infectious
diseases, to develop medical countermeasures that directly benefit patient management. IRF
projects vary widely in scope, including the discovery of candidate countermeasures, in vitro
and in vivo drug screens, the identification of candidate immune-therapeutics, the
development of candidate vaccines and clinical care paradigms, and the identification of host-
directed therapeutics. IRF undertakes research in a way that ensures that all aspects of any
given model, from in-vitro and in-vivo models to the assays selected to analyse results, are
developed to most accurately reflect human disease. Results should always be translational,
with real meaning at the bedside. Critically questioning every project as to whether the
research questions are valid and results generated will be truly useful, is paramount.

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In addition to its variety of study areas and subject matter experts, IRF was unique in the
BSL-4 community for its imaging suite, designed with animal loading zones in BSL-4 and
manning stations in the adjacent clean area. Medical imaging capabilities include PET/CT,
single photon emission computed tomography (SPECT)/CT, X-ray fluoroscopy and MRI.
Through these technologies, disease progression and response to therapeutics in animal
models can be followed and quantified in real time without reliance on animal sacrifice and
pathology reports. Medical imaging has been used with animal infections with the Nipah,
Hendra, Marburg and Ebola viruses, and numerous animal models are well developed for
each pathogen under study. Likewise, IRF also has vast in vitro drug screening capabilities
through the use of fluorescently labelled viruses.

Microbial Containment Complex, National Institute of Virology,

India
The Microbial Containment Complex of the National Institute of Virology, located in Pune,
India, conducts research on pathogens of high consequence, which provides an opportunity
for supporting public health programmes.
The BSL-4 facility in India was built with a mandate to handle clinical samples from
outbreaks caused by highly pathogenic RG4 agents. It detects, identifies, propagates and
manipulates these viruses in the laboratory to develop diagnostics, therapeutics and vaccines.
The 848-m2 BSL-4 facility was accredited in 2012, one year after the first cases of Crimean
Congo haemorrhagic fever (CCHF) were found in India. Owing to the unprecedented nature
of the outbreak, molecular evolution studies were undertaken to investigate whether cases
resulted from a bioterrorist attack. The BSL-4 laboratory developed ELISA kits and
performed serosurveillance of livestock in different districts; it noted seropositivity over the
country, especially in sheep and goats. Results indicated that the CCHF virus had probably
circulated for many years, but perhaps was masked by some other disease and not properly
detected. As differential diagnosis is a problem with this virus, due to the short incubation
period combined with similar clinical signs to dengue, the National Institute of Virology
developed an algorithm for segregating suspected CCHF patients based on retrospective
clinical and biomedical data. The laboratory provides continuous CCHF diagnostic support to
the state of Gujarat.
In addition to CCHF, the Institute has done extensive work with Kyanasur Forest disease,
which causes significant human disease and mortality. It developed multiple disease-specific
assays, including polymerase-chain-reaction(PCR)-based and serological (IgG and IgM
ELISA) tests. Through extensive epidemiological studies in wildlife, humans and ticks, the
Institute also provided critical information on seasonality of the virus in different tick species
and risky behaviour that increases the likelihood of infection.
The Institute’s BSL-4 laboratory provided multiple unforeseen benefits to the country after its
commissioning, working on outbreak investigations, testing referred clinical samples and
responding to public health emergencies, including those caused by Zika, Ebola and yellow
fever viruses. It became a poliovirus repository, including laboratory confirmation of the first
identified human cases of several viruses in India, provided the first report of H5N8 avian
19
influenza virus in India and characterized two novel virus species. In addition, it provides
technical support to medical colleges in improving laboratory infrastructure and diagnosis
and developed protocols for maintaining biosafety measures for performing tests in the
colleges.

Centre de Recerca en Sanitat Animal, Institut de Recerca i

tecnologia Agrolimentàries, Spain
Centre de Recerca en Sanitat Animal (CReSA), located in the Bellaterra quarter of Barcelona,
was created in 1999, with a biocontainment unit commissioned in 2005. The facility was
constructed as an animal BSL-3/4 facility but works with RG3 pathogens, inspired by the
Institute of Virology and Immunology Mittelhäusern design. The box-in-a-box design strictly
differentiates BSL-3 and -2 spaces. CReSA gave top priority to quality assurance from the
beginning, and received Good Laboratory Practice certification since 2009 in viral safety,
immunogenicity, administration of test products and obtaining of samples, and
immunological drug safety. CReSA was have ISO 17025 accredited in2009 in molecular and
immunological diagnosis of numerous viral diseases and prions, and earned ISO9001
certification in 2015.
The CReSA biocontainment facility was designed with flexibility and redundancy. Rather
than being built to house a specific pathogen or animal model, it is able to take up a broad
range of studies to accommodate requests from government and or researchers. Animal suites
can be modified if necessary to add equipment for work with vector-borne diseases. This
flexibility allowed CReSA to take up unforeseen opportunities; for example, although the
initial plans did not include work with vectors, requests arrived for this type of work and now
the laboratory has breeding facilities for Aedes aegypti and Anopheles stephensi for dengue
fever, yellow fever and malaria studies. In addition, it has conducted vector studies with
chikungunya fever, West Nile fever and Rift Valley fever viruses.
The biocontainment unit has designated management staff, comprising six animal care
workers and one technical coordinator. Four technical staff and a coordinator operate the
BSL-2/ 3 laboratory, and a subcontracted company provided engineering service.
The CReSA biocontainment facility serves over 70 internal users, participates in multiple
national and EU-funded projects, and provides services through private contracts. Looking to
the future, CReSA hopes to increase the participation of the BSL-3 unit in EU projects by
offering the space and expertise of the facility and to enhance relationships with private
industry for research and development work, particularly in testing vaccines and
prophylactics. Finally, the laboratory aims to be enrolled in initiatives on biocontainment,
biosafety and international biological risk management (including life-long education).

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Issues in biosafety and biosecurity in high-containment
laboratories

Establishing and maintaining biosafety and biosecurity: the

National Bio and Agro-Defense Facility, United States of America
The National Bio and Agro-Defense Facility, in Manhattan, Kansas, carried out significant
amounts of evidence-based facility engineering through the use of mock-up laboratories. This
ensured the long-term functionality of the laboratory by providing an opportunity to correct
any details with lower quality levels than expected.
As the Facility is located in a geographical area nicknamed Tornado Alley, significant
structural integrity testing was performed to evaluate the building’s ability to withstand high
wind speeds and possible projectiles without compromising negative pressure. A mock-up
laboratory space was built within a stainless-steel-and-concrete frame, containing ductwork,
electrical lines and plumbing. Pressure decay testing compared different types of concrete
with varying cure times (90 versus 180 days) and assessed varied embed types and sizes and
amounts of water stop material for their ability to maintain negative pressure.
Fibre-optic-cable installations and trench-drain options were also evaluated. Multiple readers
were utilized for the analysis, including a differential pressure manometer, temperature
thermocouple and particle counters. Overall the percentage of volume lost or gained per hour
for embeds was similar to that of a Class III Biosafety Cabinet, although atmospheric
temperature affected the phenomenon.
In addition to structural resistance against wind and projectiles, engineers at the Facility
constructed mock-ups of large-animal holding facilities to test numerous other factors,
including load testing and finishings on penning and gating materials. Further, they
performed multiple studies using tribology and tribometry to determine the best flooring for
large-animal cubicles using the American Society for Testing and Materials (ASTM) F2913–
11 testing method. Analyses were carried out with both the animals and workers caring for
them in mind, and resulted in precise formulas for the needs of different species of animals.
All the analyses carried out were compiled in a document to assist select agent regulators
during the eventual accreditation phases. Finally, the Facility’s engineering team made a
traceability matrix as a tool for regulators to disseminate best design practices.

Cooperation between scientists and engineers on laboratory

design: National Biosafety Laboratory, Hungary
The National Biosafety Laboratory, in Budapest, experienced challenges during construction
of its maximum-containment facility that pointed to ways forward. The lack of highly
specialized biocontainment engineers, combined with limited published information on the
best engineering practices and difficulty in accessing supplier networks, creates great
difficulties when constructing maximum-containment facilities in many regions of the world.
Close cooperation between scientists, engineers and designers/architects is required
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throughout all stages of laboratory creation to ensure that the construction project takes
account of users’ needs.
During initial planning stages, the creation of a user requirement specification (URS)
document can greatly facilitate understanding between scientists and engineers. The URS
reflects the primary needs of the users, taking input from management, scientists, engineers
and safety staff, and lists all features, components, process flows, and operating parameters
needed. When shared with the design team, the URS will translate to a feasible, sustainable,
safe and functional facility able to carry out its objective. As such, the scope of the facility
must be set out prior to construction, as laboratories intended for diagnostic work without
culture, and in vitro and/or in vivo research will have significantly different footprints.
Even with a well-defined URS, engineers face many challenges with high-containment
facilities. Reliance on engineering aspects (such as heating, ventilation and air conditioning
(HVAC) systems and biosafety cabinets) with increasing degrees of complexity is rising,
although little evidence is available to quantify the additional safety benefits of these layers
for staff and the environment in comparison to good microbiological practices. In addition,
while national and international guidelines on facility design may exist, they often disagree.
Energy consumption must be carefully considered for its environmental implications, as well
as operational costs. Cost-reduction strategies can include reducing the number of air changes
during off hours, use of renewable energy and power saving options, and flexibility with
HVAC, so that conditioned air is slightly warmer in the summer and cooler in the winter. The
availability of evidence-based information detailing the best methods to test the effects of
such energy-saving mechanisms on containment integrity will be critical for future
construction projects, especially in lower-resource settings.
Many challenges in the realm of maximum-containment engineering must be addressed. The
theoretical, practical and biosecurity training of engineers, upgrades of relevant international
guidelines, dissemination of evidence-based practices and increased access to supplier
networks would all facilitate the construction process. Combined with cooperation between
scientific and engineering teams, these would ensure that facilities are designed with the
primary needs of users in mind, to successfully carry out their intended mission.

Cabinet line systems: Public Health England, United Kingdom

The example of the High Containment Microbiology Department at Public Health England,
in Salisbury, provided an overview of the biosafety measures offered by the cabinet lines and
the changes required in switching to positive-pressure suits. There were currently no active
suit laboratories in the United Kingdom. The guidance of the country’s Health and Safety
Executive on the principles, design and operation of CL4 laboratories had greatly influenced
high-containment environments. While not necessarily legally binding, the guidance covered
many aspects of the requirements for BSL-4 laboratories and animal cubicles, as well as the
expectations of health and safety management.
BSL-4 cabinet lines were the current design standard for maximum-containment facilities in
the United Kingdom. Legislation required that these laboratories undergo servicing every six
months, at which time all systems were tested to EU or Public Health England standards. At
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that time, everything in the laboratory was checked and certified: including BSL-4 suite
supply and exhaust HEPA filters, pressure decay, effluent systems and autoclaves. Cabinet
lines underwent thorough testing as well, from thermal mapping of motors, testing
uninterrupted power supply, and checking seals, pressure decay, electrical and air change
rates. Worker competency was also assessed during these periods.
Frequently performing such rigorous testing basis provides many benefits. It ensures
reliability and continued operation of a laboratory; ensures protection of staff, the general
public and the environment; and provides an opportunity to trend data over time to predict the
lifetime of any given component of the laboratory. In addition, the comprehensive service
reports generated as a result provide evidence for review during regulatory audits and
demonstrate compliance with the law. The High Containment Microbiology Department’s
planned switch to a suit laboratory in its newly planned facility would require extensive
servicing and testing regimes and in-depth training of engineers to allow for maintenance and
servicing during operations.

Evidence-based biosafety: BSL-4 OIE laboratory at the Institute of

Virology, Centre for Research in Veterinary and Agronomic
Sciences, National Institute of Agricultural Technology, Argentina
The BSL-4 OIE laboratory at the Institute of Virology, Centre for Research in Veterinary and
Agronomic Sciences (CICVyA), National Institute of Agricultural Technology (INTA), in
Buenos Aires, followed evidence-based biosafety and engineering provisions at INTA.
Numerous regulatory authorities oversaw the Institute, including an Argentinian regulatory
authority that reports to OIE, and many design features and procedures were set to BMBL
and Laboratory biosafety manual standards.
The BSL-4 OIE laboratory contained two high-containment spaces, including a laboratory
and large-animal vivarium. This facility was constructed for work with many high-
consequence agricultural pathogens, although work with RG4 pathogens was not permitted.
All aspects of the laboratory were subject to a high degree of control through a building
automation system that constantly monitored and reported on critical systems, such as
airlocks, pass-throughs, security access, autoclaves and effluent treatment tanks. Redundancy
was a key theme to many of these systems, involving duplication of not only pieces of
equipment (for example, two effluent decontamination tanks) but also their key components,
such as pumps and crushers.
The BSL-4 laboratories in Argentina invested significant efforts in developing their design
and operating standards. Using OIE recommendations as a baseline, pressure differentials,
HEPA filters and other biosafety measures were selected after significant in-house testing to
ensure no loss of containment or mixing of air between rooms. For example, an air pressure
differential of –50 Pa was selected for the laboratory, even though standards require only –35
Pa. Higher air differentials were similarly selected for centrifuge rooms, viral seeding rooms
and animal suites. All air pressures were registered every two seconds, with alarms alerting to
variations of ± 10 Pa from set points. Based on its experience, INTA specifically

23
recommended the use of two different pressure references in the physical space of interest, as
opposed to ducts, relative to the outside. In addition, testing revealed that Class II A
Biosafety Cabinets were preferable to those in Class II B to avoid fluctuations in laminar
flow resulting from fluctuations in room pressure.
Detailed protocols and rationale for the transport of samples from animal cubicles to the
laboratory, selection of decontamination methods for solid effluent and large-animal waste,
disinfection of containment suites and establishment of quarantine times for vivarium staff
were also developed and described in detail. Most important was the sharing of such in-house
data with the authorities, to provide regulators with access to them.

Surge capacity: Animal and Plant Health Agency, United Kingdom

The Animal and Plant Health Agency took various engineering and procedural steps in
ramping up from a CL2 to an SAPO4 facility in the event of an outbreak.
The Agency focused on livestock production sectors, including diagnostic work, United
Kingdom surveillance, regional laboratory network, training and response to outbreak
emergencies. The facility in Weybridge, Surrey contained two high-containment laboratory
facilities operating at SAPO4/ACDP3 levels, as well as a large-animal high-containment
facility. In addition to these spaces, the building was designed with an outbreak contingency
plan in mind, where facilities normally operating at CL2 could ramp up to SAPO4 during
outbreaks of, for example, foot-and-mouth disease, classical and African swine fever, African
horse sickness virus and bluetongue virus. This was accomplished by a specially designed
CL2 facility, which operated under negative pressure at all times and contained HEPA filters
fitted to the air supply. Sealability was tested every six months to ensure that the facility
could be fumigated if needed, and effluent treatment plants, autoclaves and the incinerator
were regularly tested. The facility had not been activated to CL4 in 10 years, so training to
maintain staff competency was important. Regular, semiannual training was given for two-
week periods in mock-hot situations.
Using a two-phase activation process, the Agency could accommodate the testing of tens of
thousands of SAPO4 required-suspected samples. The first phase involved the activation of a
smaller, core suite, in which nonessential materials were removed, appropriate signage was
affixed, biosecurity was enhanced through restricted access and showers were activated, and
an effluent treatment plant switched to CL4 mode. This process required about four working
days to complete, and processing capacity could reach 40 000–60 000 samples per week.
Procedural changes accompanied the facility changes, including completely changing all
clothing, showering out, utilizing a lunchroom inside for breaks, and using pass-through
boxes and disinfectants. Sample receiving rooms and robot rooms for automated sample
processing were also utilized. When sample numbers were too high, a second extended CL4
laboratory space was added. This process required about two weeks and led to processing
scales of up to 120 000 samples per week. The Government would eventually make the
decision for the Agency to downscale and come out of outbreak mode.

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Training for high-containment laboratories: networks,
requirements and opportunities

BSL4ZNET
The training work group within BSL4ZNET had regular teleconferences with invited guest
speakers, covering topics from training and onboarding procedures, certifications and annual
refreshers, to comparisons of train-tracking software, training needs and available
opportunities. It supported laboratory exchanges between partner institutes, enhancing
personnel competency levels and promoting collaboration and capacity building between
partners. By mapping training needs and current opportunities, it identified specific gaps. In
particular, needs were identified for training in best practices in handling sharps and
conducting large-animal necropsy in BSL-4. As a result, a necropsy workshop with an
experienced pathologist was planned for February 2018 to provide hands-on training and
establish guidelines and a community of practice. Additional capacity-building projects were
planned through twinning NBAF with the National Centre for Foreign Animal Disease
laboratory in Winnipeg, Canada, where future NBAF research staff would gain practical
experience in the BSL-4 laboratory and animal cubicle through supported long-term stays.

Public Health Agency of Sweden

The Public Health Agency of Sweden, in Stockholm, developed a comprehensive BSL-4
training programme. The Swedish BSL-4 laboratory, operational since 2001, designated
training as one of its core capacities under biological risk management. The training
programme covered all appropriate laboratory personnel, including researchers, engineers
and maintenance staff, as well as biosafety professionals and laboratory managers. The
Agency organized training courses and awareness-raising campaigns for both local and
international partners, assisted the development of training tools and provided advice on
aspects of biothreats and preparedness.
Before the BSL-4 training programme was established, Agency staff visited several sites in
Europe and North America. All the trainers had experience in BSL-3 but not BSL-4;
nevertheless, many had previous scuba experience that was utilized for developing suit
training.
Several general factors should be considered in developing BSL-4 training programmes.
First, training should be integrated with specific personnel tasks, be based on scenarios, build
capacity and utilize a know–feel–do approach. In addition, it should contain both biosafety
and biosecurity components. Consideration must also be given to timing, perhaps treating
training as a continuous learning process, rather than a requirement for access. Finally,
checklists should be used to ensure that learning objectives are covered and measurable
outcomes are reached, such as enhanced individual capacity, improved teamwork and/or
greater compliance with regulations. Laboratories intending to launch external in-house
training programmes for international visitors should be aware of potential financial, legal
and security challenges.
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Further to the continuing capacity-building activities for biosafety and biosecurity, the Public
Health Agency of Sweden prioritized the development of a training curriculum for BSL-4
laboratories and the recognition of best practices. This could include a BSL-4 training
handbook, sharing of training tools and tutorials.

IEGBBR member countries

An overview of regulatory requirements related to training in IEGBBR member countries
showed that, in Asia-Pacific countries, both Australia and Singapore required training and
competency assessments for any person with access to security-sensitive biological agents,
and the regulations of both countries described the scope of training. In Japan, personnel
handling pathogens and toxins must have relevant knowledge and skills, although the specific
scope of training was not laid out.
In the Americas, Canadian regulations similarly specified the training areas required for
anyone with access to select agents and toxins, while regulations in the United States require
that any individuals approved through security risk assessment received relevant training,
though its scope was not strictly defined.
Of the European IEGGBR member countries, France had a ministerial order on training, and
Denmark required training as a licensing condition. The Netherlands Biosecurity Office
provided training workshops and electronic learning toolkits for stakeholders, and
Switzerland offered a biosafety curriculum for biosafety officers and subject-specific
curricula for various topics. Finally, the United Kingdom required safety training under the
Health and Safety Executive, though this was not specific to biosafety and biosecurity.
All IEGBBR member countries offered multiple, varied approaches to training in biosafety
and biosecurity, including formal courses, public resource documents and in-house,
institutional-level courses. National biosafety associations, the International Federation of
Biosafety Associations and EU centres of excellence offered additional training opportunities
and efforts to enhance competency in biosafety and biosecurity.

High-containment laboratories in Novosibirsk, Russian Federation

The Russian regulatory framework for high-containment facilities required national- and
institutional-level inspections of all facilities. As these facilities contained one of the two
WHO-designated smallpox reference laboratories, they were subject to annual WHO expert
review of biosafety and biosecurity. As a national mandate, all people working with highly
pathogenic organisms must go through training at least once every five years. The biosafety
department at the Russian State Research Centre for Virology and Biotechnology carried out
training of Centre personnel and researchers from other Russian federal institutes. It delivered
both site- and agent-specific training and conducted training assessments and monitoring of
personnel awareness through annual examinations. In the Russian Federation, only people
who passed these examinations were permitted to work with highly pathogenic organisms.

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BSL-4 laboratory oversight

Introduction
Speakers with diverse roles and geographical locations extensively covered the role of
competent regulatory bodies in oversight and enhancement of biosafety and biosecurity in
BSL-4 laboratories. Regulatory authorities have many public health responsibilities and
accountabilities as government or multinational agencies. Their mandates include protecting
public health, ensuring the availability and delivery of timely diagnosis and treatment, and
promoting the advancement of science and research. Their policies should advance public
health by helping to speed innovations that make diagnostics, drugs and vaccines more
effective, safe and affordable. Finally, they assist in the diffusion of accurate, science-based
information to the general public.

Federal Select Agent Program, United States of America

The Federal Select Agent Program had an important role in the regulation and oversight of
high-containment laboratories. It was a list-based regulatory programme that oversaw the
possession, use and transfer of select biological agents and toxins considered to pose severe
threats to human, animal or plant health. The list of select agents covered 66 pathogens and
toxins, with Tier-1-classified agents presenting the greatest risks of deliberate misuse with the
most significant potential consequences for public health or the economy. Any agency
wishing to work with a listed agent or toxin must be officially registered and certified.
The Division of Select Agents and Toxins of CDC was involved in the oversight of BSL-4
laboratories on numerous levels, splitting attention evenly between issues of biosafety and
biosecurity. It carried out facility inspections prior to issuing certificates of registration, upon
recommissioning of a facility, during annual inspections and following incidents or
mitigation of major containment issues. Through these inspections the Division ensured that
registered entities had appropriate measures in place to protect staff, the public and the
environment. Accordingly, it also took appropriate actions on regulatory violations, to
address identified risks and increase future compliance with the regulations of the Federal
Select Agent Program.
The inspection process reviewed several areas, including records and checks of HVAC
systems, effluent decontamination systems, building automation systems, security systems
reviews and inventory access records. Inspections were carried out to BMBL standards to
ensure that appropriate biosafety measures were in place, emphasizing proof of agent-specific
training, the use and availability of appropriate PPE, equipment certification records
(including primary containment, equipment with potential for aerosols generation and
decontamination technologies) and all specialized support systems for BSL-4 suit laboratories
and ABSL-4 facilities.
From a biosecurity perspective, the Division of Select Agents and Toxins:
• carried out security risk assessments in conjunction with the Federal Bureau of
Investigation prior to granting individual access to select agents and toxins;
27
• supported continuous monitoring and self- and peer reporting;
• had guidelines for physical laboratory security;
• oversaw agent inventory and accountability; and
• handled reports of theft, loss or release of select agents or toxins.
Since 2003, there had been no reported thefts of a select agent or toxin from a registered
entity, no deaths among laboratory workers and no reported cases of illness or death in the
general public due to work with these agents in regulated laboratories. The Federal Select
Agent Program provided guidance, training and outreach to help entities meet the
requirements of the regulations, and collaborated nationally and internationally on the
development of biosafety and biosecurity oversight programmes.

Regulators and institutional review committees in the promotion of

responsible science, Switzerland
Swiss legislation did not require an institutional biosafety committee, but every institution
must have at least one biosafety officer who liaised between national regulators, principal
investigators and laboratory personnel. A national biosafety committee of 15 experts advised
the competent regulatory agency and issued recommendations in all biosafety-related areas,
from required training to major decisions on new facility construction projects.
National regulators were well aware of what went on in which institution, but did not
influence the type of research carried out. Through their oversight roles, they aimed to
harmonize practices between laboratories through strong communication with the biosafety
officers and evaluation of institutional risk assessment and mitigation measures. Regulators in
Switzerland handled numerous authorization requests from laboratories that informed them of
the particular organisms utilized, the volumes used, genetic modifications and the publication
of scientific papers. They were also involved in making major decisions on national biosafety
issues. Examples included requirements for any future gain-of-function research with highly
pathogenic avian influenza (HPAI) to be conducted in BSL-4 facilities, despite other
countries allowing such work under enhanced BSL-3 conditions, and the designation of Spiez
as the new site for a BSL-4 facility with human pathogen capacity and of a national high-
containment laboratory network that included Spiez and the Mittelhäusern site of the Institute
of Virology and Immunology.

Regulators’ perspective
A break-out session held exclusively for regulators enabled them to discuss common
challenges and concerns in BSL-4 laboratory oversight. The discussions touched on
numerous topics, such as national standards, prescriptive versus performance-based biosafety,
training requirements, inspections, inventory control and reporting of laboratory incidents. As
legal systems and national laws and bureaucratic processes varied greatly around the world,
so did the regulatory regimes governing high-containment facilities. The regulators pointed to
numerous differences in the guidelines that shaped laboratory design and operations, the
frequency with which conformity to such regulations was officially inspected and the nature
and depth of such inspections.

28
The inspection process could comprise internal audits, federal- or state-level inspections or a
combination of both. In some cases, national frameworks granted laboratories flexibility
regarding internal audits, granting each institution the right to determine the frequency at
which they occurred. In other cases, the requirement was altogether absent. The frequency of
national BSL-4 inspections was also highly variable, ranging from twice per year to annually
to every three years.
The availability of national standards or guidelines varied greatly in different regions of the
world. Some countries, such as Canada, had established extensive legally binding standards
covering biosafety at the user, institutional and even engineering levels. Others had less
detailed national guidelines, which may or may not include requirements for facility
construction, and yet others had no specific national requirements. In many of these
instances, the WHO Laboratory biosafety manual served as an important guidance document.
The countries that had national standards varied widely in the intervals at which these were
revised.
The shift from prescriptive to performance-based regulatory approaches to biosafety was a
challenge for many regulatory bodies. Inspecting laboratories through a performance-based
approach was much more difficult for the regulator. Adding more flexibility gave more room
for interpretation; this could often lead to confusion for management and operators, which in
turn resulted in some facilities taking a more stringent approach than necessary out of fear of
possible noncompliance.
Approaches to training oversight also varied. These ranged from a requirement for agent-
specific training in some countries to a general, nonprescriptive requirement for training in
others. For countries without specific requirements, national systems allowed for institutions
to interpret international guidelines relating to the training of personnel, but each institution
was responsible for organizing training sessions and decided on content on the basis of its
own priorities. Thus, the review of documentation to ensure that training had taken place was
not a set part of all national inspection processes.
Regulations around laboratory inventory control were widely discussed. Many national
systems had diverse regulatory bodies for work with human and animal pathogens, while
zoonotic agents were often regulated on both sides. In certain countries with BSL-4-trained
inspectors, the inspection process included physical inventory checks. Depending on the
country and agency in question, there might be requirements for precise titres and volumes of
all RG4 agents, the specific number and physical locations of receptacles, passage history and
user access records. In general, even if the regulatory agency did not hold specific details of
an institute’s inventory, a designated officer within the entity was expected to have the
information accessible.
Most countries represented at the breakout session required notification of laboratory
incidents and exposures to regulating bodies, with distinctions often made between incidents
and LAIs. The timeframe within which notifications were required ranged from immediate
(made by telephone) to within two days or longer. In other cases, written records of incidents
were sufficient and provided to regulatory bodies during the auditing process, although
national records were not kept. As a result of these discussions, the regulators noted an
29
opportunity for WHO to collate global information on LAIs as a contribution to evidence-
based approaches to biosafety. Further, owing to differences in methods and attempts to carry
out root-cause analyses, WHO could further play a role in the sharing of best practices.

Operators’ perspective
In another breakout session, laboratory operators and leaders discussed aspects of the
oversight of laboratory personnel and operations, in order to compare and contrast institutes’
diverse approaches and identify best practices and common concerns to share with their
regulatory counterparts.
With the shift towards performance-based biosafety allowing laboratories more freedom,
laboratory operators had a common desire for increased interaction and discussion with
regulators, to help shape policies satisfactory to both. Operators noted that both top-down and
bottom-up approaches were employed to ensure adherence to regulations and safe laboratory
operations: some regulations came from within while others came from above.
The group considered a combination of self-auditing for continued improvement (including
yearly SOP evaluations, consultations with biosafety officers and review of laboratory
procedures to take corrective action), internal institutional reviews and external audits to be
beneficial in proactively tackling operational issues.
Inventory management systems varied greatly among BSL-4 laboratories, with each using
diverse systems with varying degrees of complication for tracking pathogen stocks. The
participants overall felt satisfied with the systems they had in place, although most felt there
was room for improvement. In addition, while no specific requirements were laid out as to
types of acceptable systems for inventory management, operators recognized the importance
of using a system that could easily be audited and said they would appreciate input on
preferences from their regulatory partners
Operators and regulators showed a major difference when pathogen-specific training was
discussed. For the operator, working safely in the environment was more important than
focusing on a specific pathogen. Some institutes had scientists working with only one
pathogen and others had groups that worked with many different agents. Thus, specific
training on the processes being carried out should have the greatest importance. The
participants in the operators’ session suggested a role for WHO in identifying potential
partners to facilitate training or establish a training network for BSL-4 facilities across the
globe, in order to harmonize best practices.
The laboratory operators were interested in the establishment of best practices for incident
response, as they were concerned about how a major incident in any BSL-4 facility could
negatively affect the entire high-containment laboratory community. They agreed that the
development of standardized plans to respond to emergencies must involve input from the
institutional biosafety committee, occupational safety and health, the CLC and local first
responders. In addition, the establishment of mechanisms and checks to ensure that laboratory
personnel were fit to work as key to incident prevention. The operators noted a large range of
approaches to making such decisions, with personality, performance and overall health as

30
influencing factors. For those granted access to BSL-4, a high level of trust between
supervisors and personnel, combined with nonpunitive reporting systems, were shared ideals
to encourage communication and ensure that laboratory personnel avoided work in
containment if they felt unwell for any reason.

Pressing issues in sharing pathogens

Nagoya Protocol
From WHO’s perspective, the Nagoya Protocol on Access to Genetic Resources and the Fair
and Equitable Sharing of Benefits Arising from their Utilization,5 a supplementary
agreement to the Convention on Biological Diversity, has the objective of ensuring fair and
equitable sharing of the benefits that arise from use of genetic resources, including access to
them. This formal agreement creates a global framework in which Member States commit
themselves to fulfilling two basic requirements:
1. prior informed consent: entities wishing to access genetic resources first obtain
permission from their country of origin; and
2. mutually agreed terms: bilateral agreement between provider and recipient on how
benefits arising from use of this material are shared with the country of origin.
At present, 101 governments had officially signed on to the Nagoya Protocol. WHO is not a
Party, but an observer of intragovernmental meetings, and provides expert scientific advice
on issues surrounding the Protocol. In response to concerns about the implications of this
agreement, WHO worked to identify areas where the Nagoya Protocol may affect public
health programmes that require access to pathogens. Study questions specifically examined
the Protocol’s implications for access to: influenza virus with pandemic potential, seasonal
influenza viruses and other pathogens that affect human health. In addition, WHO examined
the functionality of a bilateral approach versus a multilateral approach in terms of potential
bureaucratic delays that could affect response times to health emergencies.
WHO received about 30 responses from Member States, nongovernmental organizations and
vaccine companies. The results showed that the Nagoya Protocol had implications for public
health responses to infectious diseases: some positive and others causing concern. Particular
issues surrounded legal uncertainty resulting from the implementation of the Protocol, where
bilateral agreements between countries with highly diverse laws could prove highly complex
and the increased costs associated with this legal uncertainty could result in delayed
development of health countermeasures. In addition, the broad principles set out by the
Nagoya Protocol allow individual Member States to dictate how implementing legislation
will address pathogens and how to implement health emergency measures.
As article 4.4 of the Protocol specifies that, where specialized international access and
benefit-sharing frameworks exist for any particular genetic resource and are consistent with

5
The Nagoya Protocol on Access and Benefit-sharing. In: Convention on Biological Diversity [website].
Montreal, Secretariat of the Convention on Biological Diversity; 2018 (https://www.cbd.int/abs/, accessed 10
December 2018).
31
the objectives of the Protocol, such a framework would supersede the Nagoya Protocol for
that particular genetic resource. The Pandemic Influenza Preparedness (PIP) Framework, for
example, recognized by the EU as a specific framework for the transfer of pandemic
influenza virus strains, would allow EU countries to bypass the legal aspects of the Nagoya
Protocol for sharing of influenza viruses. Aside from the PIP Framework and the WHO
advisory committee presiding over all live-variola-related decisions, however, no other
pathogen-specific oversight groups existed.
The WHO report set out a number of specific actions to implement the Nagoya Protocol in
harmony with public health programmes requiring access to pathogens. These included the
promotion of dialogue, consultation, international cooperation and public awareness around
the Protocol. Articles 19 and 20 of the Protocol require each signing country to develop
guidelines, standard templates, common sets of principles and codes of conduct to clarify
rules for access to pathogen samples, and others to accelerate the sharing process.
Member States showed considerable interest in the results of the WHO study, which also
provoked further questions. These included the implications of the PIP Framework for non-
EU countries and implications for establishing sharing practices for non-influenza pathogens
and genetic data. To answer these questions, WHO worked closely with the Secretariat of the
Convention on Biological Diversity and focused particularly on genetic data. WHO also
convened consultations on the PIP Framework, had the R&D Blueprint and was developing
a tool for material transfer agreements (MTAs) that would help countries protect their
interests when bilateral agreements are made.
WHO strongly encouraged stakeholders to better understand the Protocol, as it might have
great implications for public health. The global issue of the Nagoya Protocol relating to
pathogen sharing was still at a preparatory phase, providing an opportunity to shape policy
decisions surrounding its implementation. The decisions in the future meeting relating to
pathogen sharing could have unintended consequences for public health and how
laboratories can share pathogens and/or their sequence data. The scientific community
needed to share its questions and concerns with government ministries and agencies involved
in decision-making.
The participants discussed their concerns about the consequences of the Nagoya Protocol.
For example, it might require the revision of existing arrangements between academic or
research laboratories, including memorandums of understanding and MTAs, though this
would depend on the laws of the countries concerned. Even contracts made prior to 2014
might require examination to ensure their terms were compliant with the Protocol. The
ability to access and share reference collections, critical to laboratory work around the world,
was another serious concern. While the Protocol was unlikely to affect strains pre-2014, this
would depend on regulations set out by each member country; added complications would
arise when a third country requested a genetic resource from a recipient country, rather than
the original supplier/donor country. Other potential issues arising from metagenomics
analyses and unexpected results from diagnostic samples must also be addressed.
As the number of countries that were Parties to the Nagoya Protocol continued to increase,
others would likely be constrained to join, although some developing nations might be
32
unable to do so, owing to the lack of government infrastructure. Mechanisms to assist
pathogen sharing between Parties and other countries must therefore be devised.

Shipping of Category A Infectious Substances

A review of issues surrounding the shipment of Category A (Cat A) Infectious Substances
fostered discussion on possible solutions to its overregulation. The recommendations of the
United Nations Committee of Experts on the Transport of Dangerous Goods established
tightly regulated guidelines for shipping hazardous agents and materials, with varying
requirements depending on the particular agent and sample matrix.
The most stringent regulations applied to Cat A agents, which were defined as infectious
substances transported in a form capable of causing permanent disability or life-threatening
or fatal disease in otherwise healthy human beings or animals upon exposure. Within this
category, pathogens classified as United Nations 2814 (affecting humans) and United
Nations 2900 (affecting animals only) were subject to the strictest requirements, regardless
of their form, including cultures, clinical specimens, and even suspected clinical specimens,
depending on the pathogen. Category B (United Nations 3373) material, on the other hand,
refers to biological substances, including patient specimens from HPAI infections or anthrax.
Combining the Committee of Experts’ specifications with the diverse shipping regulations of
each mode of transportation (air versus sea or land) made the transport of Cat A agents
highly complex. Very few couriers were licenced to handle these packages and enormous
paperwork and financial requirements often resulted in shipment delays. In addition, even
licenced couriers might decline to transport specific Cat A substances, which had occurred
with packages containing Ebola virus samples. On the other hand, shipping Cat B agents did
not require licenced carriers, was timely and less costly, and could be done even through
postal services. Further, aside from a difference in drop-test resistance, the packaging
requirements for Cat A and Cat B agents were essentially identical, suggesting that the same
level of risk protection was achieved in either scenario.
No documented cases had ever been recorded of accidents involving shipped infectious
substances resulting in infection of personnel. Combined with the abovementioned facts, this
raised the question as to whether the regulations surrounding Cat A shipments were truly
essential and helpful for protecting public health. If the Cat A classification were re-
examined, and agents could be shipped with the same degree of safety as Cat B agents, the
greater number of capable shippers, combined with the decreased cost, might have
significant public health benefits. As far as clinical specimens are concerned, Cat B practices
should perhaps be seriously considered for the shipping of Cat A agents. WHO hoped to
organize a stakeholder meeting on the shipment of infectious substances in the near future to
address these issues.

MTAs
MTAs needed to be well constructed, and the strategy adopted by the Institute of Novel and
Emerging Infectious Diseases at the Friedrich Loeffler Institute, in Germany, exemplified its

33
commitment to public sharing. MTAs between high-containment laboratories serve many
important purposes, from virus discovery, to the development and validation of assays, to
animal studies. They should be designed for two different scenarios – normal business and
emergency situations – as stated in the Nagoya Protocol. Material to be shared includes
samples, pathogens, antibodies and genetic constructs. Ultimately, the capability for material
exchange and transfer is a key performance indicator of international research agencies;
those incapable of it are probably not fit to play a great role in international interventions.
In the past, collaboration had often been collegial; materials were transferred based on
mutual trust, scientific interest and ethical values. This sort of collaboration was more
difficult at present, as institutions usually had formal systems, profit interests and reputations
to uphold. Governance issues could also complicate material transfers, as the ultimate
signing authority was not always clear and responsibilities towards third parties might come
into play. In addition, issues surrounding the place of jurisdiction, claims for damages and
guarantees of material fitness might have legal implications. Further, approaches to dealing
with legal issues varied between continents.
The Friedrich Loeffler Institute was a recently constructed facility for research and diagnosis
of high-risk animal pathogens. In addition to significant BSL-3 and BSL-3+ large-animal
cubicle spaces, the Institute was the only maximum-containment facility in Europe with
capacity for large-animal BSL-4 work. In addition to work in Europe, the Institute
participated in several international collaborations and had received a total of 25 000
mammalian samples from African partner countries between 2013 and 2017. This was
largely achieved through the Institute’s simplified approach to MTAs, which had removed
any clauses related to profit orientation and government issues. An MTA contained 10
simple clauses pertaining to ownership of original material, use for noncommercial purposes,
liability for fitness of the material, confidentiality and proprietary aspects of the results
obtained. In its MTA, the Institute granted the beneficiary ownership of all research results,
sought no royalties, permitted publications with written approval and stated that material
should be destroyed at the study’s conclusion, although no time stipulations were attached.
The use of simplified MTAs with plain language that regulate only truly relevant issues can
greatly facilitate collaboration. Having a streamlined internal MTA process with downgraded
authorization procedures can shorten timelines, simplify negotiations and increase the
likelihood of successful collaboration.

Building confidence between high-containment

laboratories and the global community: cultivating a
safety-oriented culture

Public Health Agency of Sweden

Intensive risk communication by the Public Health Agency of Sweden changed the
community’s perception of its BSL-4 laboratory from a high-risk to a high-security facility,

34
seen as a resource rather than a threat. Since opening the laboratory 2001, the Agency had
invested heavily in promoting biosafety and training through many activities, including the
establishment of a Nordic biosafety network, development and delivery of the first
postgraduate biosafety course in Sweden, capacity-building projects and involvement in
workshops of the European Committee for Standardization (CEN).
The BSL-4 laboratory had been fully operational for 16 years, contained two fully functional
BSL-4 units and had hosted eight onsite training courses for international participants. During
this period, it had had zero shutdowns, zero biosecurity breaches and zero major staff
incidents. There was a nearly 100% (assumed) reporting of deviations in the BSL-4
laboratory, a much higher rate than in lower-containment areas. Having the right people in all
areas of laboratory operations and ensuring their willingness to interact were key to success.
Other critical factors included a solid research, diagnostics and biosafety infrastructure;
permanent financial support through government funding; long-term strategies for national
preparedness; and international collaboration.
BSL-4 laboratories should prioritize particular areas to increase confidence with the global
community. The first was performance-based validation of risk management. Having
validation mechanisms in place increased the implementation of a safety-oriented culture and
the likelihood of collaboration with other laboratories. Sharing of best practices, from
biosafety measures to inactivation procedures and training resources to facility operations,
was another key means for BSL-4 laboratories to build trust. Participating in formal
laboratory networks and establishing bilateral memoranda of understanding were excellent
means to this end.
Finally, as described by CEN workshop agreement 15793 on laboratory biorisk management
provisions, BSL-4 laboratories must make personnel reliability assessments to ensure that
staff are fit for the job and would promote the Agency. The Agency employed a thorough
screening process, generating an overall candidate profile based on health checks and medical
examinations, background checks and behaviour-based screening. Psychological assessments
were included to assess emotional stability, capacity for communication and cooperation,
judgment, integrity and capacity to resist external pressure, acceptance of and capacity to
follow instructions, and an active approach to safety and security management.

KCDC, Republic of Korea

National and institutional systems fostered a culture of biosafety in the Republic of Korea.
Biosafety and biosecurity were part of the national budget and were governed by numerous
regulatory acts. All laboratories in the country must be registered with the appropriate
ministries governing the use of pathogens with which they worked.
Laboratories required ministerial approval before starting work with RG3 and RG4
pathogens, and must apply for reauthorization every three years. Those dealing with high-
consequence pathogens were subject to regular inspections of facilities, operations and
biosafety and biosecurity management.

35
The county made significant investments in enhancing biosafety and biosecurity. Numerous
published national guidelines specified containment levels, standards for animal facilities and
biosafety and security in general, and even the verification processes for high-containment
facilities. Annual education and training were required for all research and laboratory staff,
and biosafety training workshops and conferences were regularly held for research personnel.
Targeted efforts to enhance institutional biosafety committees included professional training
and national workshops for their members, and the development and distribution of
guidelines for the committees.
At KCDC, biosafety systems were governed at the national (BSL-4 certification, revalidation,
inspection, biosafety education) and institutional levels (SOP development, education,
training, and emergency-response drills). The BSL-4 training process was highly structured,
with general theoretical training provided to all new staff, followed by practical training in a
mock laboratory and significant onsite training by experienced supervisors. Overall, scientific
staff participated in over 80 hours of training prior to testing and task-specific certification.
Regular incident-response training and emergency drills familiarized workers with
emergency procedures and evacuation routes, and periodic reassessment and retraining of
existing staff ensured that knowledge and skills remained up to date. Within the institution,
management and biosafety officials ensured attention to biosafety during the development of
SOPs, by holding periodic meetings for dialogue between stakeholders, and continuing to
improve the expertise of the institutional biosafety committee.
Through a combination of national, institutional and internal regulations, the KCDC BSL-4
laboratory was committed to a culture of biosafety, leading to safer science and building
confidence and trust in the global high-containment community.

CDC, United States of America

The BSL-4 research groups at CDC took a particular approach to achieving a safety-focused
culture. Many research groups studying diverse pathogens occupied CDC's high-containment
facility. To improve coordination between the many stakeholders, CDC established a high-
containment laboratory operations group as a forum to discuss scheduling requirements, set
standards for routine training, guide protocol and manual development, and ensure safe
working practices. Members included representatives of research staff, the sections dealing
with animal care, engineering and security, the internal select agent programme and linked
parties. CDC linked the high-containment operators with upper management by creating a
high-containment laboratory governance council with representatives of CDC management,
biosafety and security, and the high-containment laboratory operations group. This council
approved policies, set priorities for the high-containment laboratory and resolved issues on
which the operations group could not reach consensus.
CDC applied a standard training regimen for the BSL-4 laboratory. All staff received initial
training on general entry/exit and emergency procedures from the office of laboratory safety,
and annual refresher training thereafter. Each research programme then offered pathogen-
specific training, beginning with practical training in BSL-2 and followed by closely
monitored, mentor-based training in BSL-3 and -4. CDC stipulated a minimum number of
36
required hours or training sessions prior to granting individual access, although mentors
might require additional entries before deeming a person competent to work alone.
CDC enforced a regular standard review procedure for many critical procedures. A laboratory
safety review board examined all SOPs on an annual basis, conducted quarterly reviews on
records of material inactivation and removal from BSL-4, assessed validation data for
inactivation protocols and approved inactivation SOPs. Drills on emergency procedures were
reviewed annually, and staff competency was regularly assessed; other BSL-4 research
groups peer reviewed the study plans of BSL-4 research programmes.

Biosafety controls for newly emerging pathogens in a

limited-resources setting

The final speaker challenged the participants to resolve a scenario-based dilemma: the
selection of biosafety controls and laboratory handling procedures for the diagnosis of an
unknown pathogen in a limited-resource setting.
The selection of biosafety and containment measures is usually based on an understood or
assumed level of risk associated with the material, and greatly influenced by a number of
factors, such as the location of testing (in the field versus on site), availability of resources
and information to work with, cost considerations, time pressures to provide results, political
and community consent, and legislative requirements. When the agent is unknown, the
determination of risk is often based on extrapolation from what is known of similar
pathogens. In other cases, even this may not be possible. Well-equipped BSL-4 laboratories
allow for a broader range of manipulations than work in the field, where limited risk
mitigation measures accommodate only methodologies that do not require pathogen
propagation.
In countries such as New Zealand, which had no RG4 endemic organisms, laboratorians
neither expected nor were accustomed to handling materials containing such organisms.
Nevertheless, increasing border pressure due to international travel (where ill visitors or
returning travellers may present with symptoms questionable for high-consequence
pathogens) presented a need for RG4 diagnostic capabilities in nonendemic countries. In
response to this pressure, New Zealand was building a high-containment enhanced CL3+
facility, to contain a separate high-biosafety laboratory suite with BSL-4 design features,
where initial diagnostic screening using inactivation methods could be performed. In
anticipation of future activities, the participants were asked to describe appropriate biosafety
controls and guidance to laboratorians dealing with suspected diagnostic samples of
potentially uncharacterized RG4 agents.
The participants strongly recommended that a rigorous training programme, including risk
assessment training and biosafety cabinet training, be required. Building on this, pairing staff
inexperienced in high-containment work with experienced mentors would build the former’s
confidence in using enhanced PPE and other procedures specific to high containment.

37
The majority of participants strongly encouraged the use of inactivating agents, with
suggestions including immediate inactivation at the field collection site or the use of partial
inactivation methods, such as Triton X-100 in the case of Ebola virus, which greatly reduce
virus titre and infectivity without interfering with biochemical tests. Other options include the
addition of inactivating buffers directly to vacutainer tubes, and a method developed by the
National Centre for Virology in India: a one-minute inactivation method that does not
interfere with downstream nucleic acid or serological testing. Alternatively, and perhaps
ideally, initial samples from an unknown suspected outbreak situation should be immediately
aliquoted with a portion inactivated and sent for next-generation sequencing characterization,
while the remainder is stored safely in its nascent form until further information is acquired.
While some participants felt that attempts to propagate unknown samples could be considered
when associated case fatality rates are not unusually high, others called for caution in testing
samples for known/expected agents, rather than the unknown. For example, at the US
Department of Agriculture attempts to propagate suspected porcine reproductive and
respiratory syndrome virus samples in cell culture revealed co-infection with Reston
ebolavirus, an agent with no prior history of swine or other livestock infection. Ultimately,
having well established SOPs in place that account for process-associated risks in different
scenarios is key to guiding staff in their initial decision-making. Beyond the facility level,
having well established relationships between laboratories would provide remarkable strength
to collaborative international responses to outbreaks.

Collaboration between high-containment facilities and

WHO: moving forward

The coming together of participants from over 50 countries for the WHO Consultative
Meeting on High/Maximum Containment (Biosafety Level 4) Laboratories Networking
resulted in intense discussions from operators’ and regulators’ perspectives. All participants
showed keen interest in collaborative opportunities in areas ranging from scientific research
and training to recruitment strategies, operations and facility design. Discussions highlighted
several critical points where commitment from networking partners and WHO is required to
strengthen the global BSL-4 community in moving forward.

Creation of a community of practice

With the unprecedented expansion of BSL-4 laboratories worldwide, opportunities and
mechanisms to promote the sharing of best practices would lead to enhanced biosafety and
biosecurity as early as the planning stages. Many critical areas were noted, including:
• the efficacy of inactivation methods, with a focus on effects on infectious dose;
• the environmental impact of chemically inactivated waste;
• the validation of chemical showers;
• waste disposal plans for emergency situations, such as excessive waste from Ebola
patients;

38
• information on facility engineering, operations and maintenance for new projects in the
design stage;
• facility decommissioning;
• strategies for community engagement and messaging on working together for responsible
science;
• the availability of countermeasures or postexposure protocols for LAIs;
• recruitment strategies for new laboratories;
• inventory management systems;
• incident response plans;
• auditing and regulations; and
• tools and metrics for risk assessment.

Facility sharing
Collaborative facility sharing for operator cross-training would increase capacity and
confidence building in the BSL-4 community. It would be especially important when new
laboratories were constructed, so that new recruits could gain real experience prior to
working in their own facilities. Participants suggested twinning through bilateral agreements
as the best approach. Further, a commitment from BSL-4 laboratories to provide surge
capacity for other countries was warranted in anticipation of future emergencies.

Mapping of training opportunities

The importance of training for laboratory operators and facility staff was among the most
discussed topics at the Meeting. The participants identified numerous gaps in BSL-4 training,
from the identification of best training practices and maps of training opportunities and
rosters of expert trainers to institutional assessment mechanisms to demonstrate
comprehensive and effective training programmes. They repeatedly stressed the value of
creating a platform to map training opportunities and share best practices.

Sample sharing
With complications likely to arise from the ratification of the Nagoya Protocol, there was a
need to establish sample sharing frameworks that include legal conditions. Suggestions
included placing certain pathogens in the public domain, and establishing a set of laboratory
strains without consensus on ownership that could be shared without any conditions.

International recognition of BSL-4 laboratories

Differences in national regulatory systems and guidelines led to varied interpretations of
requirements for BSL-4 facilities and programming between countries using the WHO
Laboratory biosafety manual as a guidance document and those employing particular
national frameworks. The rapid expansion of BSL-4 laboratories, combined with a lack of
internationally designated inspection teams, had resulted in a certain level of mistrust
between well established and newly operational facilities. New facilities in countries without

39
strong international research networks met hesitation from international partners about
admission to cooperative and collaborative agreements, particularly on material sharing,
even when significant investments in biological risk management had been made. As a
result, there was a clear need to establish baseline standards for an acceptable BSL-4 facility.
The participants encouraged WHO to take part in designating a formal group of international
experts to perform site visits and officially vouch for facilities and their operations.

Suggested future roles and responsibilities for WHO

The participants suggested that WHO take on or continue several initiatives to support the
global BSL-4 community of practice. These included:
• facilitating collaboration between high-containment laboratories;
• identifying competent partners to provide global biosafety training ;
• mapping and coordinating existing networks;
• continuing messaging on the revised Laboratory biosafety manual;
• gathering data on LAIs and incidents on a global scale; and
• designating and deploying experts for validation of and expertise sharing with new BSL-4
laboratories.
The participants expressed an overwhelming interest in a WHO-coordinated, designated web
space to serve as an information hub for BSL-4 laboratories, which would facilitate the
dissemination of data and access to network partners to all members of the BSL-4
community.

40
Annex 1. Agenda

Day 1: Wednesday, 13 December

Topics Speakers
Registration of participants
Opening remarks Guenael Rodier
• Meeting objectives and expected outcomes Florence Fuchs
• Introduction of chairperson for the day and rapporteur Sébastien Cognat
• Housekeeping announcement Kazunobu Kojima

Keynote talk Jim LeDuc

WHO Laboratory biosafety manual revision and high-

containment approaches
• Revision principles, concepts, and updates Kazunobu Kojima
• Biosecurity level 4 (BSL-4)/high-containment/varying Kathrin Summermatter
approaches
• Open discussion
Activities of other organizations, networks and their role
regarding high containment work
• World Organization for Animal Health Christine Uhlenhaut
• International Expert Group on Biosafety and Biosecurity Thomas Binz
Regulation
• Biosafety Level 4 Zoonotic Laboratory Network Primal Silva
• Group of High-Containment Laboratory Directors Christine Bruce
• Quality Assurance Exercises and Networking on the Detection Antonino Di Caro
of Highly Infectious Pathogens
• European Research Infrastructure on Highly Pathogenic Hervé Raoul
Agents
Activity update: planned, under construction, newly
constructed and established high-containment laboratories
• High-containment laboratories planned
o Nagasaki University, National Research Centre for the Jiro Yasuda
Control and Prevention of Infectious Diseases BSL-4,
Japan
o Chinese Center for Disease Control and Prevention, China Zhao Chihong
o Centre for Emergency Preparedness and Response, Public Allen Roberts
Health England, United Kingdom
• High-containment laboratories under construction
o Institute Pasteur de Côte d’Ivoire, Ministry of Higher Mireille Dosso
Education and Scientific Research, Côte d’Ivoire
o National Bio and Agro-Defense Facility, Department of Eugene Cole
Homeland Security, United States of America
41
 o High Containment Large Animal Facility, Pirbright Institute, Michael Johnson
United Kingdom
• Newly constructed high-containment laboratories
o Chinese National High Containment Facilities for Animal Zhigao Bu
Diseases Control and Prevention, Harbin Veterinary
Research Institute, China
o National Biosafety Laboratory, Wuhan Institute of Virology, Yuan Zhiming
Chinese Academy of Sciences, China
o Osong BSL-4 Laboratory, Korea Centers for Disease Min Woo Park
Control & Prevention, Republic of Korea

o Victorian Infectious Diseases Reference Laboratory, Julian Druce

Australia
o Centre for Biological Threats and Special Pathogens, Andreas Kurth
Robert Koch Institute, Germany
• Established high-containment laboratories moving into the
future
o Commonwealth Scientific and Industrial Research James Watson
Organization, Australia
o US Army Medical Research Institute of Infectious Sina Bavari
Diseases, United States of America

New laboratories and public opinion: earning support and

trust of the public
• Allocation of funds for construction and operation Ronald B. Corley
• Addressing diverse opinions of citizens Masayuki Saijo
• Communication with community
• Maintaining support through showing a safety record to the
public and good laboratory practice
Unique opportunities enabled by high-containment facilities to
advance global health
• Research on pathogens of high consequence Lisa Hensley
• Capacity to develop and test novel therapeutics D.T. Mourya
• Ability to address recently identified global health threats F. Xavier Abad
• Opportunities to safely conduct high-risk research Morejón de Girón

Day 2: Thursday, 14 December

Topics Speakers
Recap of Day 1 Day 1 chairperson
(Bryan Charleston)
Appointment of chairperson Kazunobu Kojima
Overview of the Nagoya Protocol and how it relates to high- Jakob Quirin
containment laboratories

42
Shipment of Category A infectious substances Kazunobu Kojima
• Associated challenges
• Perceived benefits and enhancements to safety
• Value in expanding or limiting the scope of the programme
Establishing and maintaining biosafety and biosecurity in
high-containment laboratories: engineering
• Evidence-based facility engineering Eugene Cole
• Adaptability to meet changing scientific needs
• Dissemination of best laboratory design practices Zoltan Kis

Selection of biosafety measures approved, validated and

implemented at high-containment laboratories
• Heating, ventilation and air conditioning (HVAC) system and air Samuel Edwin
pressure cascade
• Positive pressure suit system Allen Roberts
• Cabinet line system
• Chemical shower system Juan Manuel
• Access controls implemented to maintain security Schammas
• Discussion on best containment practices for vivariums
Shared challenges and opportunities for strengthening high-
containment laboratories
• Surge capacities Steve Lever
o Readiness strategies for sample influx
o Streamlined processing of samples Wendy Shell
o Lines of communication for laboratory coordination
• Roles of regulators and institutional review committees in the
promotion of responsible science Thomas Binz
o Improved communication among stakeholders
o Value of diligence by an institutional review committee Giuseppe Ippolito
o Mitigated risks in favour of scientific benefits
Laboratory oversight and biosafety enhancement: the
regulator’s perspective (meeting room 1) Session chair:
Mary Louise Graham
• Laboratory oversight: compliance monitoring and verification
o Intercountry comparison of standards for effective and
achievable engineering controls
o Oversight of laboratory training programmes
o Inventory management systems for dangerous pathogens
o Inspections
• Laboratory incident and exposure response
o Identification of best practices for incident reporting
o Identification of best practices for exposure reporting
o Corrective actions to address the root cause
o Encouraging reporting while discouraging non-reporting

43
Laboratory oversight and biosafety enhancement: the
operator’s perspective (meeting room 2) Session chair:
Bradley Pickering
• Oversight of laboratory personnel
o Adherence to regulations and safe laboratory operation
o Inventory management policies that reflect regulations
o Mentored pathogen-specific training
• Plan–do–check–act of laboratory operations
o Identification of best practices for incident response
o Establishment of trust between the supervisor and
laboratory personnel
o Reviews of laboratory procedures to correct deficiencies
o Self-/internal auditing mechanism to ensure continual
improvement
Laboratory oversight and biosafety enhancement plenary Breakout session
session chairpersons

Establishing and maintaining biosafety and biosecurity in

high-containment laboratories
• Training
o Identification of best training practices Primal Silva
o Institutional assessment mechanisms to improve training Sergei N.
o International network of training: mapping of training Shchelkunov
opportunities and roster of trainers Åsa Szekely Björndal
o Evidence demonstrating establishment of comprehensive
and effective training programmes in a laboratory Su Yun Se Thoe
o Regulatory requirements in different countries
Confidence building between high-containment laboratories
and global community
• Framing the recognition of laboratories with demonstrated Åsa Szekely Björndal
proficiency in biosafety and biosecurity
o Metric utilized to assess safe laboratory operation
o Assessment of laboratory personnel training
o Framework for recognition of laboratories
• Cultivating a safety-oriented culture in high-containment Haesun Yun
laboratories
o Guidance establishing laboratory review committees and Victoria Olson
biosafety offices
o Approach to support laboratories
• Material transfer between high-containment laboratories Martin Groschup
o Procedures to facilitate the development of research
programmes in the growing high containment community

44
Day 3: Friday, 15 December
Topics Speakers
Recap of Day 2 Day 2 chairperson
(Stephan Gunther)
Appointment of chairperson Kazunobu Kojima
Biosafety controls for newly emerging pathogens
• Consensus on initial biosafety controls employed Joseph O’Keefe
• An optimized approach to handling clinical samples and Amadou Alpha Sall
conducting research in varying settings
Collaboration between high-containment facilities and WHO: Day 3 chairperson
open discussions for identifying mechanisms that promote: (Mary Louise Graham)
• increased access through collaborative facility sharing
• sharing of best biosafety and biosecurity practices
• mapping of training opportunities
• global consensus outlining biosafety and biosecurity
• identification of WHO’s role in facilitating collaboration between
high-containment laboratories
Summary, recommendations and plan of action Mary Louise Graham
• Summary
• Discussion
• Conclusions and recommendations
• Future plan of action
Adjournment

45
Annex 2. Summary of biosecurity level 4 (BSL-4)
laboratories in the planning or operational phases as of
December 2017, based on available information

Institute/Organization Country BSL Operational Laboratory Human WHO

status type or region
animal
Institute of Virology, National Argentina 3+ Operational – Animal Americas
Institute of Agricultural
Technology (INTA)
National Food Safety and Argentina 3+ Operational – Animal Americas
Quality Service (SENASA)

Australian Animal Health Australia 4 Operational Suit Animal Western

Laboratory, Commonwealth (ABSL4) Pacific
Scientific and Industrial
Research Organization
(CSIRO)
Emerging Infectious Diseases Australia 4 Operational Suit Human Western
and Biohazard Response Unit Pacific
(EIBRU), Westmead Hospital
Victorian Infectious Diseases Australia 4 Newly Suit Human Western
Reference Laboratory constructed Pacific
(VIDRL), Peter Doherty
Institute for Infection and
Immunity
Pan American Foot-and- Brazil 3+ Operational – Animal Americas
Mouth Disease Center
(PANAFTOSA)
National Centre for Foreign Canada 4 Operational Suit Human Americas
Animal Disease, Canadian
Food Inspection Agency
National Microbiology Canada 4 Operational Suit Human Americas
Laboratory (NML), Public (ABSL4)
Health Agency of Canada
Chinese Center for Disease China 4 Planned Suit Human Western
Control and Prevention, Pacific
Beijing China BSL-4
Chinese National High China 4 Newly Suit Animal Western
Containment Facilities for (ABSL4 constructed Pacific
Animal Diseases Control and and
Prevention, Harbin Veterinary BSL4)
Research Institute
Wuhan Institute of Virology, China 4 Newly Suit Human Western
Chinese Academy of Sciences constructed Pacific
Institut Pasteur de Côte Côte d'Ivoire 4 Under Suit Human Africa
d'Ivoire, Ministry of Higher Construction
Education and Scientific
Research

46
Institute/Organization Country BSL Operational Laboratory Human WHO
status type or region
animal
Department for Biological Czech 4 Operational Suit Human Europe
Defence, Military Institute of Republic
Health
Laboratory for Biological Czech 4 Operational Suit Human Europe
Monitoring and Protection, Republic
National Institute for Nuclear,
Chemical, and Biological
Protection
National Veterinary Institute, Denmark 3+ Operational – Animal Europe
Technical University of
Denmark
Jean Mérieux Laboratory P4, France 4 Operational Suit Human Europe
National Institute of Health
and Medical Research of
France (INSERM)
Bernhard Nocht Institute for Germany 4 Operational Suit Human Europe
Tropical Medicine
Fredrich Loeffler Institute Germany 4 Operational Suit Human Europe
(FLI), Federal Research
Institute for Animal Health
Institute for Virology, Philipps Germany 4 Operational Suit Human Europe
University of Marburg
Robert Koch Institute Germany 4 Newly Suit Human Europe
constructed
National Biosafety Laboratory Hungary 4 Operational Suit Human Europe
(OKI), National Public Health
Institute (former National
Center for Epidemiology)
Microbial Containment India 4 Operational Suit Human South-East
Complex (MCC), National Asia
Institute of Virology
High Security Animal Disease India 3+ Operational – Animal South-East
Laboratory, National Institute Asia
of High Security Animal
Diseases (NIHSAD)
Lazzaro Spallanzani National Italy 4 Operational Suit Human Europe
Institute for Infectious
Diseases
L. Sacco University Hospital, Italy 4 Operational Suit Human Europe
University of Milan
Nagasaki University BSL-4, Japan 4 Planned Suit Human Western
Nagasaki University Pacific
National Institute of Infectious Japan 4 Operational Cabinet line Human Western
Diseases (NIID) Pacific
National Biocontainment New 3+ Operational – Animal Western
Laboratory, Ministry for Zealand Pacific
Primary Industries
Osong BSL-4 Laboratory, Republic of 4 Newly Suit Human Western
Korea Centers for Disease Korea constructed Pacific

47
Institute/Organization Country BSL Operational Laboratory Human WHO
status type or region
animal
Control and Prevention
(KCDC)

Federal Budgetary Research Russian 4 Operational Suit Human Europe

Institution – State Research Federation
Centre of Virology and
Biotechnology VECTOR,
Russian Federal Service for
Surveillance on Consumer
Rights Protection and Human
Wellbeing (Rospotrebnadzor)
National Health Laboratory, Saudi Arabia 4 Planned Suit Human Eastern
Saudi Ministry of Health Mediterran
ean
Special Pathogens Unit, South Africa 4 Operational Suit Human Africa
National Institute for
Communicable Diseases
(NICD) in South Africa
Centre for Research into Spain 3+ Operational – Animal Europe
Animal Health (CReSA),
Autonomous University of
Barcelona (UAB) and the
Institute of Agri-food
Research and Technology
(IRTA)
Unit of Highly Pathogenic Sweden 4 Operational Suit Human Europe
Microorganisms, Department
of Preparedness, Swedish
Institute for Communicable
Disease Control
Institute of Medical Virology, Switzerland 4 Operational Suit Human Europe
University of Zurich
Institute of Virology and Switzerland 3+ Operational – Animal Europe
Immunology (IVI), Federal
Department of Home Affairs
Laboratory of Virology, Switzerland 4 Operational Suit Human Europe
Geneva University Hospitals
Animal and Plant Health United 4 Operational Suit Human Europe
Agency (APHA), Department Kingdom
for Environment, Food, and
Rural Affairs (DEFRA)
Centre for Emergency United 4 Operational Cabinet line Human Europe
Preparedness and Response, Kingdom
Public Health England (PHE)
Defence Science and United 4 Operational Suit Human Europe
Technology Laboratory Kingdom
(DSTL), Ministry of Defence
High Containment Large United 4 Under Suit Human Europe
Animal Facility (HCLAF), Kingdom Construction
Pirbright Institute

48
Institute/Organization Country BSL Operational Laboratory Human WHO
status type or region
animal
National Institute for United 4 Operational Suit Human Europe
Biological Standards and Kingdom
Control (NIBSC), Department
of Health
Rocky Mountain Lab (RML), United 4 Operational Suit Human Americas
National Institute of Allergy States of
and Infectious Diseases America
(NIAID)
National Biodefense Analysis United 4 Operational Suit Human Americas
and Countermeasures Center States of
(NBACC) America
Foreign Animal Disease United 3+ Operational – Animal Americas
Diagnostic Laboratory States of
(FADDL), Plum Island America
Galveston National United 4 Operational Suit Human Americas
Laboratory, University of States of (BSL4
Texas Medical Branch America and
ABSL4)
Viral Immunology Center, United 4 Operational Cabinet line Human Americas
Georgia State University States of
America
Integrated Research Facility at United 4 Operational Suit Human Americas
Fort Detrick, National Institute States of
of Allergy and Infectious America
Diseases (NIAID)
Special Pathogens Branch, United 4 Operational Suit Human Americas
Centers for Disease Control States of
and Prevention America

Texas Biomedical Research United 4 Operational Suit Human Americas

Institute States of
America
National Emerging Infectious United 4 Newly Suit Human Americas
Diesease Laboratories States of constructed
(NEIDL), Boston University America
US Army Medical Research United 4 Operational Suit Human Americas
Institute of Infectious States of
Diseases (USAMRIID), US America
Department of Defense
Plum Island Animal Disease United 3+ Operational Animal Americas
Center, US Department of States of
Homeland Security America
National Bio and Agri-Defense United 4 Under Suit Animal Americas
Facility (NBAF), US States of (ABSL4) Construction Laboratory
Department of Homeland America
Security

49
Annex 3. Participants6

Argentina
Mr Ezequiel Matias Roqueiro, Biosafety Officer, National Food Safety and Quality Service
(SENASA), Buenos Aires
Mr Juan Manuel Schammas, Biosafety Responsible Official, Institute of Virology, National
Institute of Agricultural Technology (INTA), Buenos Aires

Australia
Dr Julian Druce, Head of Virus Identification Laboratory, Victorian Infectious Diseases
Reference Laboratory (VIDRL), Peter Doherty Institute for Infection and Immunity,
Melbourne
Dr Vitali Sintchenko, Director, Centre for Infectious Diseases and Microbiology – Public
Health, University of Sydney, Westmead
Dr James Watson, Veterinary Investigation Leader, Australian Animal Health Laboratory,
Commonwealth Scientific and Industrial Research Organization (CSIRO), Geelong

Brazil
Dr Ottorino Cosivi, Director, Pan American Foot-and-Mouth Disease Center
(PANAFTOSA), Rio de Janeiro*

Canada
Dr Bradley Pickering, Lead Scientist BSL-4 Program, National Centre for Foreign Animal
Disease, Canadian Food Inspection Agency, Winnipeg
Dr David Safronetz, Chief of Special Pathogens, National Microbiology Laboratory (NML),
Public Health Agency of Canada, Winnipeg
Dr Primal Silva, Chief Science Operating Officer, Science Branch, Canadian Food Inspection
Agency, Ottawa and Biosafety Level 4 Zoonotic Laboratory Network (BSL-4ZNET)

China
Professor Zhigao Bu, Director-General, Harbin Veterinary Research Institute, Chinese
Academy of Agricultural Sciences
Dr Jinxiong Liu, Associate Professor, Harbin Veterinary Research Institute, Chinese
Academy of Agricultural Sciences
Dr Zhiming Yuan, Director, National Biosafety Laboratory, Wuhan Institute of Virology,
Chinese Academy of Sciences

6
Participants listed with an asterisk were invited but unable to attend.
50
Dr Chihong Zhao, Director, Office of Laboratory Management, Chinese Center for Disease
Control and Prevention, Beijing

Côte d'Ivoire
Professor Dr Mireille Dosso, Director, Institute Pasteur Côte d'Ivoire, Abidjan

Czech Republic
Dr Michal Kroca, Director, Department for Biological Defence, Military Institute of Health,
Techonin
Dr Michal Dřevínek, Laboratory for Biological Monitoring and Protection, National Institute
for Nuclear, Chemical and Biological Protection, Milin

Denmark
Dr Kirsten Tjørnehøj, Senior Advisor Biosafety, National Veterinary Institute, Technical
University of Denmark, Lindholm

France
Dr Hervé Raoul, Director, Laboratory P4 Jean Mérieux, National Institute of Health and
Medical Research of France (INSERM), Lyon

Germany
Dr Markus Eickmann, Head of BSL-4 Containment Laboratory, Institute for Virology,
Philipps University of Marburg*
Professor Dr Martin H. Groschup, Head, Institute of Novel and Emerging Infectious
Diseases, Friedrich Loeffler Institute, Federal Research Institute for Animal Health, Isle of
Riems
Professor Dr Stephan Günther, Head of Department of Virology, Bernhard Nocht Institute for
Tropical Medicine, Hamburg
Dr Andreas Kurth, Head, Biosafety Level-4 Laboratory, Centre for Biological Threats and
Special Pathogens, Robert Koch Institute, Berlin

Hungary
Dr Zoltan Kis, Head, National Biosafety Laboratory, National Public Health Institute (NPHI),
Budapest
Dr Bernadett Pályi, Biosecurity Officer, NPHI, Budapest

51
India
Dr D.T. Mourya, Director, Microbial Containment Complex (MCC), National Institute of
Virology, Pune
Dr V.P. Singh, Director, National Institute of High Security Animal Diseases, Anand Nagar,
Bhopal

Italy
Dr Antonino Di Caro, National Institute for Infectious Diseases, Lazzaro Spallanzani, Rome
Professor Maria Rita Gismondo, Chief of Clinical Microbiology, Virology and
Bioemergency, L. Sacco University Hospital, Milan
Dr Giuseppe Ippolito, Scientific Director, National Institute for Infectious Diseases Lazzaro
Spallanzani, Rome

Japan
Professor Daisuke Hayasaka, Associate Professor, National Research Center for the Control
and Prevention of Infectious Diseases (CCPID), Nagasaki University
Dr Masayuki Saijo, Director, Department of Virology, National Institute of Infectious
Diseases (NIID), Tokyo
Professor Jiro Yasuda, Director, BSL-4 Facility Project Office, CCPID, Nagasaki University

Netherlands
Mr Douwe Kuperus, Biosafety Officer, Wageningen Bioveterinary Research

New Zealand
Dr Joseph O'Keefe, Director, National Biocontainment Laboratory Project, Wallaceville

Republic of Korea
Mr Min Woo Park, Staff Scientist, Division of Bioterrorism Preparedness and Response,
Korea Centers for Disease Control and Prevention (KCDC)
Dr Haesun Yun, Scientist, Division of Biosafety Evaluation and Control, KCDC, Korea
National Institute of Health

Russian Federation
Professor Sergei N. Shchelkunov, Head, Department of Genome Studies and Development of
DNA Diagnostics of Poxviruses, Federal Budgetary Research Institution – State Research
Centre of Virology and Biotechnology VECTOR, Russian Federal Service for Surveillance
on Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor), Koltsovo

52
Saudi Arabia
Dr Waleed Saleh Alsalem, Chief Executive Officer, National Health Laboratory, Ministry of
Health, Riyadh*

Senegal
Dr Amadou Alpha Sall, Institut Pasteur in Dakar (WHO Collaborating Centre for Reference
and Research of Arboviruses and Viral Haemorrhagic Fever Viruses)

South Africa
Professor Janusz T. Paweska, Head, Centre for Emerging Zoonotic and Parasitic Diseases,
National Institute for Communicable Diseases (NICD), Sandringham-Johannesburg*

Spain
Dr F. Xavier Abad Morejón de Girón, Head, Biocontainment Unit, Centre for Research into
Animal Health, Institute of Agri-food Research and Technology, Barcelona

Sweden
Dr Åsa Szekely Björndal, Officer/Senior Expert Advisor, Institutional Biosafety, Public
Health Agency of Sweden (PHAS), Stockholm
Dr Åsa Rosenquist, Head, Unit for Diagnostic Preparedness of Notifiable and High
Consequence Pathogens, PHAS, Stockholm

Switzerland
Dr Pascal Cherpillod, Biosafety Officer, Laboratory of Virology, Geneva University
Hospitals
Dr Michael Huber, Institute of Medical Virology, University of Zurich
Dr Kathrin Summermatter, Head Biosafety and Deputy Director, Institute of Virology and
Immunology (IVI), Federal Department of Home Affairs, Mittelhäusern

United Kingdom
Dr Christine Bruce, Head of Operational Delivery, National Infection Service, Public Health
England (PHE), Salisbury
Dr Bryan Charleston, Director, National Institute of Bioscience, Pirbright Institute
Dr Michael Johnson, Director of Capability, National Institute of Bioscience, Pirbright
Institute
Dr Steve Lever, Principal Scientist, Defence Science and Technology Laboratory (DSTL)
Porton Down, Salisbury

53
Dr Allen Roberts, Director, High Containment Microbiology Department, PHE, Salisbury
Dr Wendy Shell, Bio Risk Manager, Safety, Health and Well-being (SHaW), Animal and
Plant Health Agency (APHA), Addlestone
Dr Matthew Smith, SAPO4 Facility Manager/Head of Pandemic Flu Are, National Institute
for Biological Standards and Control (NIBSC), Potters Bar

United States of America

Dr Sina Bavari, Chief Scientific Officer/Scientific Director, US Army Medical Research
Institute of Infectious Diseases (USAMRIID), Frederick
Mr L. Eugene Cole II, Program Technical Director, Program Executive Office, National Bio
and Agri-Defense Facility (NBAF), Science and Technology Directorate, US Department of
Homeland Security, New York
Dr Ronald B. Corley, Director, National Emerging Infectious Disease Laboratories (NEIDL),
Boston University
Dr Robert Davey, Director ABSL4, Department of Virology and Immunology, Texas
Biomedical Research Institute, San Antonio
Dr J. Patrick Fitch, Director, National Biodefense Analysis and Countermeasures Center
(NBACC), Fort Detrick
Dr Elaine Haddock, Senior Research Assistant, Rocky Mountain Laboratories (RML),
National Institute of Allergy and Infectious Diseases (NIAID), Hamilton
Dr Lisa Hensley, Associate Director for Science, Integrated Research Facility, NIAID, Fort
Detrick
Dr Julia Hilliard, Director, Viral Immunology Center, Georgia State University, Atlanta
Dr James LeDuc, Director, Galveston National Laboratory, University of Texas Medical
Branch
Dr Charles Lewis, Foreign Animal Disease Diagnostic Laboratory (FADDL), United States
Department of Agriculture, Plum Island
Dr Victoria A. Olson, Chief, Poxvirus and Rabies Branch, National Center for Emerging and
Zoonotic Infectious Diseases, Division of High-Consequence Pathogens and Pathology,
Centers for Disease Control and Prevention (CDC), Atlanta

Other organizations

International Expert Group on Biosafety and Biosecurity Regulation (IEGBBR)

Dr Thomas Binz, Head, Section Biological Safety and Human Genetics, Federal Office of
Public Health, Federal Department of Home Affairs, Liebefeld, Switzerland
Dr Samuel S. Edwin, Director, Office of Public Health Preparedness and Response, Division
of Select Agents and Toxins, CDC, Atlanta, United States of America

54
Dr Tatsuhiro Isogai, Director, Infectious Diseases Information Surveillance Office,
Tuberculosis and Infectious Disease Control Division, Health Service Bureau, Ministry of
Health, Labour and Welfare, Tokyo, Japan
Ms Relus Kek, Public Health Group Biosafety Branch, Ministry of Health, Singapore
Dr Gary Lum, Principal Medical Adviser, Office of Health Protection, Department of Health,
Canberra, Australia
Dr Yann Meslier, Inspector, Inspection Division, French National Agency for Medicines and
Health Products Safety (ANSM), Saint-Denis, France*
Dr Keith Stephenson, Intervention Programme Manager, Microbiology and Biotechnology
Unit, Health and Safety Executive, Leeds, United Kingdom
Dr Su Yun Se Thoe, Deputy Director, Public Health Group Biosafety Branch, Ministry of
Health, Singapore

World Organization for Animal Health (OIE)

Dr Christine Uhlenhaut, Coordinator, Scientific Committee, Paris, France

WHO Collaborating Centre for biosafety and biosecurity

Ms Mary Louise Graham, Director, Centre for Biosecurity, Office of Biosafety and
Biocontainment Operations, Public Health Agency of Canada, Ottawa, Canada

Rapporteur
Dr Samantha Kasloff, Postdoctoral Fellow, National Centre for Foreign Animal Disease,
Canadian Food Inspection Agency, Winnipeg, Canada

World Health Organization

Headquarters
Dr Guy Boivin
Dr Sebastien Cognat
Dr Pierre Formenty*
Dr Florence Fuchs
Dr Matthew Huante
Dr Kazunobu Kojima
Ms Dhamari Naidoo*
Mr Jakob Quirin
Dr Guenael Rodier, Director, Country Health Emergency Preparedness and IHR

*
* unable to attend
55
Regional Office for Europe
Dr Joanna Zwetyenga, Division of Communicable Diseases and Health Security

56