BioRisk | De [=23 (20 | 7) Apeer-reviewed open-access journal

doi: 10.3897/biorisk.12.12156 REVIEW ARTICLE & B lO Re IS k

www.pensoftonline.net/biorisk

Global Trends in Biorisk Management

Sreenivas Reddy Bathula'*, A. Rakhimol!

| Department of Biotechnology, Bapuji Institute of Engineering and Technology, Davanagere - 577004,
Karnataka, India 2 SAVI EASY LIFE s.r.0., Praha 5, 15000, Czech Republic

Corresponding author: Sreenivas Reddy Bathula (jaishwa@hotmail.com)

Academic editor: J. Spangenberg | Received 7 February 2017 | Accepted 17 June 2017 | Published 14 July 2017

Citation: Bathula SR, Rakhimol A (2017) Global Trends in Biorisk Management. BioRisk 12: 1-23. https://doi.
org/10.3897/biorisk.12.12156

Abstract

This report recapitulates the diverse aspects of biological safety. Biological laboratory is a space that fa-
cilitates the handling and storage of microorganisms, their components or their derivatives. Laboratories
that handle dangerous pathogens have to act in a responsible manner to manage the safety and security
threats posed by these pathogens. This necessity was foreground in the December 2008 World at risk
report, which specifically demanded bioscience laboratories that handle dangerous pathogens to imple-
ment a unified laboratory biorisk management framework to enhance their safety and security. The report
also discusses the guidelines of biosafety regulations provided by World Health Organization (WHO)
that are necessary to adequately and sustainably manage these biorisks and helps in better understanding
of risk governance approaches for laboratories that handle dangerous pathogens to achieve the ultimate
goal of minimizing or preventing the occurrence and consequences of human error within the laboratory
environment: the biorisk management approach, composed of biosafety, laboratory biosecurity and ethi-
cal responsibility. It preferably provides an agreement between authorities, the public, and the scientific
community establishing trust and societal safety and security, while enabling the continued progress of
science. Biorisk management approach demonstrates that biorisks in all their potential forms are appro-
priately addressed, managed and minimized. Thus, biorisk management has become an important aspect
of the development and sustainability of biological activities.

Keywords

Biorisk, Biosafety, biosecurity, biosafety level laboratories and laboratory management

Copyright S.R. Bathula,A. Rakhimol. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY
4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..

2 Sreenivas Reddy Bathula & A. Rakhimol / BioRisk 12: 1-23 (2017)

Introduction

Management of biological safety and security risks is a difficult and costly venture. It
requires a comprehensive system incorporating the most important aspects of biorisk
which encompasses both policy and management aspects. Biorisk governance aims at
providing a framework for an organization to enable biorisk assessment and biorisk
management activities to take place in a sustainable way. It not only improves decision
making, planning and prioritisation, but also contributes to a more efficient allocation
and use of the valuable biological materials (VBM) within a laboratory. Biorisk man-
agement, thus creates value by ensuring that the resources are efficiently used and thus
guarantee the achievement of the strategic objectives (Fig. 1).

Biorisk governance is based on detailed risk assessment, sound decision making,
strict and consistent implementation of appropriate risk mitigation measures, moni-
toring and reviewing (Fig. 2).

Biorisk assessment forms the basis of biorisk management. Biological risk assess-
ment is a legal obligation in many countries that have biosafety regulations, as part of
the notification or authorization process and/or as a basis to determine the required
containment levels and other protective or preventive measures. It is also a major ele-
ment of the WHO laboratory biosafety manual and a basis of the laboratory biorisk
management standard CWA 157937.

Biosafety and biosecurity are the two components of biorisk (WHO 2004).

Biorisk Management =

AA ad — pa tachatat Be

Identify
the risk
factors

Monitor
and
review

VWVho
can be

; ' harmed
Management seach accent
Standards

Record your
findings Evaluate
the risks

Dr: Dina Ramadan
Microbiologist
Quality manager ,central health laboratory

Figure |. AMP model of biorisk management.

Global Trends in Biorisk Management 3
Understanding

Pre-Assessment

~

Mi anagement(” Communicaton ‘') Appraisal

Lharacternsaton
and Evaluation

Figure 2. Biorisk governance process.

Biosafety

The World Health Organization issues a practical guidance from which the under-
standing of biosafety on techniques for use in laboratories is derived. The WHO Labo-
ratory biosafety Manual (LBM) considers biosafety to be “the containment principles,
technologies and practices that are implemented to prevent unintentional exposure
to pathogens and toxins, or their accidental release.” The LBM contains expert guid-
ance on how to implement the relevant principles, technologies and practices. The
WHO encourages all states to consider such concepts when developing and enhancing
national regulatory regimes. The international guidance is then tailored to fit precise
national requirements. Such concepts are consistent across public, animal and plant
health sectors and close cooperation between the WHO, FAO and OIE contributes to
the development of relevant guidance and understandings. Biosafety is one term that
is used to describe the policies and procedures adopted to ensure the environmentally

safe application of modem biotechnology (WHO 2014).

Biosecurity

The term biosecurity is more complex as it can have different meanings in different
contexts. In the Biological Weapons Convention (BWC) setting, it is most commonly

4 Sreenivas Reddy Bathula & A. Rakhimol / BioRisk 12: 1-23 (2017)

used to refer to mechanisms to establish and maintain the security and oversight of
pathogenic microorganisms, toxins and relevant resources. The implications of bios-
ecurity in public health settings, however, relate more closely to the BWC. Laboratory
biosecurity describes “the protection, control and accountability for valuable biological
materials within laboratories, in order to prevent their unauthorized access, loss, theft,
misuse, diversion or intentional release.” Biosafety is one term that is used to describe
the policies and procedures adopted to ensure the environmentally safe.

Finally, it is important to note that concern about risks to human health and to the
environment is not peculiar to biotechnology. Rather, these questions have emerged
as an important component in the development, regulation and promotion of the
products of many new and older technologies such as chemicals and pharmaceuticals.

2.1 Laboratory practices

2.1.1 Personal protective equipment

Personal protective equipment (PPE) is an essential element laboratory safety, and
must be provided to all staff members by their respective institutions free of charge.
PPE provided to staff members includes, but is not limited to:

¢ Gloves

e Disposable or reusable laboratory coats (impervious to liquids)
e Side shields (for glasses)

e Face shields

e Surgical masks

e Safety glasses

¢ Prescription safety glasses

° Goggles

¢ Hoods

e Shoe covers

¢ Respiratory protection (e.g., N95 respirator)
e Other site-specific PPE

At a minimum, laboratory personnel shall wear gloves and a laboratory coat when-
ever handling biological agents, cells and tissues. Safety glasses with side shields, gog-
gles, or face shield shall be worn when these materials could potentially be splashed in
the face. Laboratory personnel shall wear other personal protective equipment (apron,
face shield, surgical mask, N95 respirator, etc.) as needed or required to prevent poten-
tially infectious materials from reaching their clothes, skin, eyes, mouth, or other mu-
cous membranes. PPE must be removed prior to leaving the work area and placed in
designated areas. PPE must be treated as medical waste when discarded. If PPE is not
disposable, PPE shall be cleaned with disinfectant before and after use or laundered by
an outside vendor by placing it into designated biohazard bags provided by the vendor.

Global Trends in Biorisk Management 5

2.1.2 Biological safety cabinets

Biological safety cabinets (BSCs) provide a primary level of containment for working
safely with potentially hazardous biological materials. When combined with standard
microbiological practices, BSCs can protect both laboratory personnel and the envi-
ronment. Although many may think that the principle function of BSCs is to protect
cells and cultures from contamination by bacteria and fungi, their primary purpose
should be to protect the laboratory workers and the environment from exposures to
potentially infectious agents.

BSCs are designated as Class I, H, or HI based on specific airflow patterns within
the BSC and on the locations of high efficiency particulate air (HEPA) filters within
the unit. HEPA filters are usually composed of a pleated sheet of borosilicate fiber
material that has been treated with a wet-strength water-repellant binder. These filters
are specifically designed to remove particles equal and greater than 0.3 microns with
an efficiency of 99.97%. This filtration level will capture bacteria, spores, and viruses
from the filtered air (Fig. 3).

Implementation of the following procedures will ensure optimal operation of a
BSC and maintain product, personnel and environmental protection:

e Front and rear grills should be free of clutter to allow proper air intake.

e Sash should not be raised above the specified level.

e Personal protective equipment (laboratory coat or gown, gloves) must be worn
in order to maintain product and personnel protection.

e Work surfaces must be disinfected before and after working in the BSC.

¢ Bunsen burner use will cause airflow disruptions and damage to the HEPA
filter and potentially cause a fire, and should be avoided.

¢ Certification must be performed annually.

Biosafety
Cabinet

la Room Air
IS Cortaminated Air
- Negative pressure
Gg Contaminated Air
- positive pressure t
MM) HEPA Filtered Air

Figure 3. Airflow Pattern in Biosafety Cabinet.

6 Sreenivas Reddy Bathula & A. Rakhimol / BioRisk 12: 1-23 (2017)

BSCs are required to be tested and certified annually by technicians accredited by the
National Sanitation Foundation (NSF International). Additionally, BSCs will be certified
when they are first installed and whenever they are moved, even to a nearby laboratory,
because the HEPA filters may be dislodged from their proper fitting during these moves.

2.1.3 Disposal of biological waste

Biological waste may be disposed of in three ways: designated biological waste box, chemical
disinfection, and steam sterilization/autoclave. Appropriate disinfection procedures will be
chosen and utilized in accordance with both the Principal Investigator (PI) and the Biologi-
cal Safety Officer (BSO) in order to ensure adequate decontamination of biological wastes.

Infectious and potentially infectious non-sharp waste and waste containing rDNA
may only be disposed of in designated biological waste boxes. Each box is labeled with
the universal biohazard symbol and is lined with two red plastic bags to reduce the
likelihood of leakage. When a biological waste box is between two thirds (2/3) and
three-quarters (3/4) full, the two bags should be individually sealed with tape and the
box itself sealed with two-inch tape. Do not overfill the boxes. Boxes that leak any liq-
uid or that exceed 55 pounds will not be moved or removed for disposal.

Liquid biological and rDNA waste must be rendered non-infectious by steam
sterilization or chemical disinfection prior to sink disposal. If chemical disinfection is
selected, full-strength household chlorine bleach may be added to the waste container,
such as an aspiration flask, so that the final solution concentration of bleach will be
10%. Contact time should be at least 30 minutes prior to sink disposal for bleach. Use
bleach that is labeled “mercury-free”.

Before disposing of the treated solution down the sink, check the pH to ensure it
is within the permissible pH range. If it is within the permissible range, then disposal
of the treated solution in the sink should be done with running tap water to minimize
possible plumbing damage due to the corrosive effects of the disinfectants. Autoclav-
ing solutions containing bleach is not permitted due to the potential for production of

toxic chlorine gas (National Select Agent Registry, CDC 2016).

2.1.4 Biological/radionuclide waste

Biological/Radionuclide Waste, disinfect the infectious material with chemical disin-
fectant and dispose of as chemical waste. Select chemical disinfectants carefully because
some disinfectants can react with chemicals.

2.1.5 Sharps management

Some of the most serious accidents in biological laboratories are those caused by punc-
ture wounds through skin (percutaneous exposures). All objects that can puncture skin

Global Trends in Biorisk Management 7

are designated as sharps and require special disposal treatment. Examples of sharps in-
clude hypodermic needles, glass Pasteur pipettes, razor blades, broken glass and suture
needles. Sharps must be disposed of separately from all other waste streams and sharps
containers cannot be disposed of with other biological waste. Federal regulations con-
cerning sharps primarily focus on work with human bodily fluids. Research work con-
ducted with animals only is not required to utilize engineered safety sharps; however,
it is recommended that engineered devices be used whenever practical. Because the
majority of laboratory biohazard injuries are due to hypodermic needles, special atten-
tion has focused on their use and disposal. Some guidelines include:

e Minimize use of needles and syringes.

¢ Do not bend, shear, or break needles.

¢ Do not recap needles.

¢ Do not remove needles from syringes.

¢ Dispose of the entire syringe-needle combination in a sharps container.

e Be careful during cleanup; some sharp items may be hidden in the waste
materials.

e Ifa needle stick occurs, encourage the wound to bleed for a few minutes, wash
the area, and then get medical attention immediately. In 2001, in response to
the Needle stick Safety and Prevention Act, OSHA revised the BBP Standard
29:'CPR 191021030.

2.1.5.1 Sharps disposal

To prevent injury from sharps, place all needles, Pasteur pipettes, syringes, suture nee-
dles, scalpels, and razor blades into standard sharps containers. Large volumetric/sero-
logical pipettes, or other items that can puncture the biological waste red bags should
be disposed of in Sharps containers. Sharps containers must be red, fluorescent orange
or orange-red leak proof, rigid, puncture-resistant, shatterproof containers that that
are marked prominently with the universal biohazard warning symbol and the word
“Biohazard” in a contrasting color. Place sharps containers in convenient locations
near work areas so they will be used. Do not overfill the sharps containers. Containers

should be sealed when they are three-quarters (3/4) full.

2.1.5.2 Broken and clean glassware disposal

Place clean glassware into the standard recycling boxes for glassware. Contaminated
broken test tubes or other broken glass items must be placed directly into sharps
containers.

2.1.5.3 Pasteur pipettes disposal

Pasteur pipettes are a special case because Massachusetts law requires that they be con-
sidered as a sharps waste no matter what their previous use. Discard glass Pasteur
pipettes directly into sharps containers; do not use broken glassware boxes. Plastic
pipettes and serological pipettes that could puncture the red waste bags should also be
disposed of in sharps containers.

8 Sreenivas Reddy Bathula & A. Rakhimol / BioRisk 12: 1-23 (2017)

2.1.6 Disinfection and decontamination

Disinfection and decontamination are terms that are often used interchangeably, but
they each have specific definitions. Disinfection is a chemical or physical treatment
that destroys most biological agents, except spores. Decontamination refers to a chemi-
cal or physical treatment that destroys most biological agents to a low level, but not
necessarily zero. A number of disinfectants are commonly used in laboratory settings,
particularly to wipe down surfaces to remove infectious agents.

2.1.6.1 Autoclaving procedures

Autoclaves work by denaturing biological molecules with superheated steam; dry heat
is not nearly as effective. For example, it takes 12 minutes to kill most spores with
steam at 121 degrees Celsius (°C), while 6 hours are required with dry heat at the same
temperature. It is the steam that kills.

As a result, anything that does not come in contact with steam inside the autoclave
may not be adequately decontaminated. The potential for inadequate decontamina-
tion becomes a greater concern when sealed biohazard bags are placed in an autoclave.
There are two simple solutions:

1. carefully cut open the bag, or

2. place about 200 milliliters of water in the bag before sealing. Typically, bags
(24” x 36”) of solid plastic waste take from 45 minutes to 1 hour to reach
sterilizing temperatures throughout its contents.

2.1.6.2 Autoclave testing and validation
Autoclaves should be tested quarterly and validated to insure that they are oper-
ating properly and killing the biological organisms in each autoclave load. The
preferred method for autoclave validation is to test it with a commercial spore
test system. This system uses ampoules containing a bacterial species called Bacil-
lus stearothermophilus that is tolerant to high temperatures and contains a color
indicator solution. The ampoules are autoclaved under realistic conditions, such
as in the middle of a bag of waste, and then incubated for two days at 56°C. If
the spores grow, a color change will occur indicating inadequate sterilization in
the autoclave. If there is no growth, no color change occurs and the autoclaving
procedure is adequate. Frequent validation is not necessary, unless required by
regulatory authorities in special circumstances. By using an established autoclave
test procedure, quarterly checks with a biological indicator usually adequate to as-
sure proper autoclave function and to detect gradual deterioration of operation. It
is important to note that autoclave tape indicates only that a critical temperature
was reached; it does not indicate the length of time at the desired temperature or
whether steam was present.

The following tips will help prevent injury and property damage when using the
autoclave.

Global Trends in Biorisk Management 9

¢ Do not overfill containers. Leave the top third as empty expansion space.

e Use only vented closures so that steam may enter the load.

e Place contaminated materials in autoclave bags. Place bags inside plastic or
metal trays when autoclaving.

e Use only containers designed for sterilization. Use plastic or metal trays.

e When opening the autoclave, wear appropriate PPE as items may be hot to
the touch.

2.1.7 Spill management
Management of Small Spills (spills 100 ml)

The following procedures are recommended for a large volume biological spill in
the laboratory area, in a BSC, or if equipment malfunctions while processing biologi-
cal materials:

e If the spill occurs in a BSC, close the sash and leave the BSC running.

¢ Keep people out of the area to prevent spread of the contamination. Put up
a warning sign indicating that there was a spill in the BSC, the steps taken to
treat/contain the spill, and contact information for a responsibly party.

e Remove any contaminated clothing and put it into a biohazard bag for decon-
tamination later.

e Wash hands and exposed skin thoroughly with soap and water.

3. Biorisk assessment

Risk assessment is the backbone of the practice of biosafety. While there are many tools
available to assist in the assessment of risk for a given procedure or experiment, the most
important component is professional judgment. Risk assessments should be based on
the specific characteristics of the organisms being considered for use, the equipment
and procedures to be employed, animal models that may be used, and the containment
equipment and facilities available. The performed risk assessments should be reviewed
routinely and revised when necessary, taking into consideration the acquisition of new
data having a bearing on the degree of risk and other relevant new information from the
scientific literature. One of the most helpful tools available for performing a microbio-
logical risk assessment is the listing of risk groups for microbiological agents. However,
simple reference to the risk grouping for a particular agent is insufficient in the conduct
of a risk assessment. Other factors that should be considered, as appropriate, include:

1. Pathogenicity of the agent and infectious dose
2. Potential outcome of exposure
3. Natural route of infection

10 Sreenivas Reddy Bathula & A. Rakhimol / BioRisk 12: 1-23 (2017)

4, Other routes of infection, resulting from laboratory manipulations (parenteral,
airborne, ingestion)

AN

Stability of the agent in the environment

6. Concentration of the agent and volume of concentrated material to be ma-
nipulated

7. Presence of a suitable host (human or animal)

8. Information available from animal studies and reports of laboratory-acquired
infections or clinical reports

9. Laboratory activity planned (sonication, aerosolization, centrifugation, etc.)

10. Any genetic manipulation of the organism that may extend the host range of
the agent or alter the agent's sensitivity to known, effective treatment regimens

11. Local availability of effective prophylaxis or therapeutic interventions

4.The laboratory biorisk management approach

Laboratory biorisk management is fundamentally a culture of rigorously assessing
risks, deciding how to mitigate those risks deemed to be unacceptable and establishing
mechanisms to constantly evaluate the effectiveness of the control measures.

4.1 Hazard Analysis

In order to determine which practices and procedures are required when working with
biological materials, a risk assessment should be conducted. Based on an agent-based
biorisk assessment that includes laboratory biosecurity considerations, laboratories
containing Valuable Biological Materials (VBM) should develop systems and controls
to provide the required degree of assurance that biosafety and laboratory biosecurity
risks are appropriately managed, and that the consequences of release of any VBM
from the laboratory are appropriately minimized. (http://www.biosecurity.sandia.gov/
BioRAM/Biorisk%20Framework%20Report.pdf)

Managing these risks represents:

1. Reducing the risk of unintentional exposure to pathogens and toxins or their
accidental release (biosafety), and reducing the risk of unauthorized access,
loss, theft, misuse, diversion or intentional release of VBM to tolerable, accept-
able levels (laboratory biosecurity).

2. Providing assurance, internally and externally (facility, local area, government,
global community, etc.), that suitable measures have been adopted and effec-
tively implemented.

3. Providing a framework for continuous awareness-raising for biosafety, labora-
tory biosecurity and ethical code of conduct, and training within the facility.

Global Trends in Biorisk Management i

The present document does not provide prescriptive guidance on the development
of laboratory biosecurity measures, but describes recommendations and performance
expectations, placing responsibility on national authorities and facility managers to
demonstrate that appropriate and reasoned biorisk minimization procedures have been
established and will be implemented. These recommendations do not call for compli-
ance with a set of requirements, but rather help to identify and set goals to be achieved.
This approach allows countries and facility managers to define and choose appropri-
ate systems and controls to ensure that the biorisk management goals that have been
identified are reached. It allows institutions to adapt their laboratory biosecurity plans
to their particular situation.

4.2 Securing valuable biological materials (VBM)

Laboratory biosecurity is more than just the safeguarding of dangerous pathogens and
toxins from individuals or organizations who would use them for harm. While protec-
tion of dangerous pathogens and toxins is obviously appropriate, the scientific, medi-
cal and pharmaceutical communities should also consider protecting materials with
historical, medical, epidemiological, commercial or scientific value. These decisions
should be taken with due consideration to the fact that scientists serve only as tempo-
rary custodians of valuable scientific assets whose past and current value to science may
be understood, but whose utility for the future can only be estimated.

Some VBM have intrinsic value and they need to be preserved for study by future
generations of scientists. Their transfer and sharing should be encouraged or main-
tained as long as appropriate documentation allowing to track them is available. Thus
scientists have a duty to maintain VBM according to current best practice. Ifa decision
is taken to destroy unwanted or unnecessary materials, protocols must be followed
to ensure their full and complete destruction and documentation. The protection of
VBM includes appropriate storage conditions, documentation of their storage, use,
transfer to more appropriate laboratories, or proof of complete destruction.

The classification of biological materials as VBM should be left to their caretak-
ers (laboratory managers and scientists) who should know and understand their value
and should be able to address and define the level of protection required. To address
these issues, the caretakers of VBM should consult with partners, e.g. in the research
community and in the security, intelligence or information technology (IT) sectors to
ensure the protection of their valuable assets against identified biorisks. If the facility
holding the collection cannot ensure its protection, the laboratory manager together
with the responsible scientist(s) should make arrangements to safely transfer them to a
more secure site. In this way, policy-makers, scientists, laboratory directors and security
engineers, supported by journal editors and publishers of research results, may achieve
an appropriate balance between the protection of VBM and the preservation of an
environment that promotes legitimate microbiological research.

12 Sreenivas Reddy Bathula & A. Rakhimol / BioRisk 12: 1-23 (2017)

All microorganisms, natural or laboratory-modified, may be included in the broad
definition of VBM. Although some agents have heightened capacities to cause harm if
intentionally misused, virtually all may have legitimate uses for medical, commercial
and scientific applications. Their value should prompt a responsibility to limit op-
portunities for VBM to be inappropriately accessed while at the same time preserve
opportunities for their study and legitimate use, e.g. for the development of improved
vaccines, diagnostics and therapies, work that requires handling, using, transporting,

transferring and sharing of VBM.

5. Guidelines for basic level laboratories

A very specialized research laboratory that deals with infectious agents is the biosafety
lab. Whether performing research or production activities, when working with in-
fectious materials, organisms or perhaps even laboratory animals, the proper degree
of protection is of utmost importance. Protection for laboratory personnel, the envi-
ronment and the local community must be considered and ensured. Biological safety
levels are ranked from one to four and are selected based on the biological agents or
organisms, work practices, safety equipment and facility design on which the research
or work is being conducted. Each level up builds on the previous level, adding con-
straints and barriers (http://www.cdc.gov/biosafety/). (Table 1)

The four biosafety levels were developed to protect against a world of select
agents. [hese agents include bacteria, fungi, parasites, prions, rickettsial agents and
viruses, the latter being probably the largest and most important group. In many
instances the work or research involves vertebrate animals, everything from mice to
cattle. When vertebrates are involved, additional precautions and safety requirements
are necessary. Using the most infectious agents also means extensive security measures
are in place, not only because of their virulence but also because of their potential for
use in bioterrorism.

5.1 Biosafety level laboratories

5.1.1 Biosafety level 1

Biosafety level one, the lowest level, applies to work with agents that usually pose
a minimal potential threat to laboratory workers and the environment and do not
consistently cause disease in healthy adults. Research with these agents is generally per-
formed on standard open laboratory benches without the use of special containment
equipment. BSL 1 labs are not usually isolated from the general building. Training on
the specific procedures is given to the lab personnel, who are supervised by a trained
microbiologist or scientist. Standard microbiology practices are usually enough to pro-
tect laboratory workers and other employees in the building.

Global Trends in Biorisk Management 13

Table |. Description of biosafety level laboratories.

Biosafety level BSL-1 BSL-2 BSL-3 BSL-4
* No Contamination * Containment ¢ High Containment * Max Containment
Hanae Defined Organisms * Moderate Risk * Aerosol Transmission ¢ “Exotic”, High-Risk Agents
: Oa. Disease of varying severi Rap vy eee rte * Life-threatening disease
disease arying Y disease 8
ae es, Ecoli Influenza, HIV, Lyme Disease Tuberculosis Ebola Virus
. ' Indigenous or exotic agents, Dangerous & exotic agents
Agents that present Agents associated with human 6 6
i Ses tomer ee eta ca etn agents that present a potential _that pose a high risk of
Pathogen type ‘patil a cendl® Metide fe esate Sethe for aerosol transmission, & aerosol transmitted laboratory
ee i ea ans : agents causing serious or infections & life-threatening
potentially lethal disease. disease.
Autoclave None None Pass-thru autoclave with Bioseal Pass-thru autoclave with Bioseal
requirements required in laboratory room. required in laboratory room.

The guidance and recommendations given as minimum requirements pertaining
to laboratories of all biosafety levels are directed at microorganisms in Risk Groups
1-4. Although some of the precautions may appear to be unnecessary for some organ-
isms in RiskGroup1, they are desirable for training purposes to promote good micro-

biological techniques (GMT).

5.1.2 Biosafety level 2

Diagnostic and health-care laboratories (public health, clinical or hospital-based) must
all be designed for Biosafety Level 2 or above. As no laboratory has complete control
over the specimens it receives, laboratory workers may be exposed to organisms in
higher risk groups than anticipated. This possibility must be recognized in the de-
velopment of safety plans and policies (https://www.eolss.net/sample-chapters/C17/
E6-58-01-08.pdf).

Biosafety level two would cover work with agents associated with human disease,
in other words, pathogenic or infectious organisms posing a moderate hazard. Exam-
ples are the equine encephalitis viruses and HIV when performing routine diagnostic
procedures or work with clinical specimens. Therefore, because of their potential to
cause human disease, great care is used to prevent percutaneous injury (needlesticks,
cuts and other breaches of the skin), ingestion and mucous membrane exposures in
addition to the standard microbiological practices of BSL 1. Contaminated sharps are
handled with extreme caution. Use of disposable syringe-needle units and appropriate
puncture-resistant sharps containers is mandatory. Direct handling of broken glass-
ware is prohibited, and decontamination of all sharps prior to disposal is standard
practice. The laboratory’s written biosafety manual details any needed immunizations
(e.g., hepatitis B vaccine or TB skin testing) and whether serum banking is required
for at-risk lab personnel. Access to the lab is more controlled than for BSL 1 facilities.

14 Sreenivas Reddy Bathula & A. Rakhimol / BioRisk 12: 1-23 (2017)

==>

SL

Biosafety Level 2

AVINORUWED PERS One

Figure 4. Biosafety level 2.

Immuno compromised, immune suppressed and other persons with increased risk for
infection may be denied admittance at the discretion of the laboratory director (Fig. 4).

BSL 2 labs must provide the next level of barriers, mainly safety equipment and fa-
cilities. Preferably biosafety cabinet, autoclave and other decontamination equipments,
first aid kits and a readily available eyewash station is needed. Self closing lockable
doors and biohazard warning signs are also required at all access points.

5.1.3 Biosafety level 3

The containment laboratory — Biosafety Level 3 is designed and provided for work with
Risk Group 3 microorganisms and with large volumes or high concentrations of Risk
Group 2 microorganisms that pose an increased risk of aerosol spread. Biosafety Level
3 containment requires the strengthening of the operational and safety programmes
over and above those for basic laboratories — Biosafety Levels 1 and 2. The guidelines
given above are presented in the form of additions to those for basic laboratories — Bi-
osafety Levels 1 and 2, which must therefore be applied before those specific for the
containment laboratory — Biosafety Level 3.

Yellow fever, St. Louis encephalitis and West Nile virus are examples of agents re-
quiring biosafety level 3 practices and containment. Work with these agents is strictly
controlled and must be registered with all appropriate government agencies. These are
indigenous or exotic agents that may cause serious or lethal disease via aerosol trans-
mission, i.e., simple inhalation of particles or droplets. The pathogenicity and commu-
nicability of these agents dictates the next level of protective procedures and barriers.
Add to all the BSL 2 practices and equipment even more stringent access control and
decontamination of all wastes, including lab clothing before laundering, within the lab

Global Trends in Biorisk Management LS:

Figure 5. Biosafety level 3 laboratory.

facility. Baseline serum samples are collected from all lab and other at-risk personnel
as appropriate.

More protective primary barriers are used in BSL 3 laboratories, including solid-front
wraparound gowns, scrub suits or coveralls made of materials such as Tyvek® and respira-
tors as necessary. Facility design should incorporate self-closing double-door access sepa-
rated from general building corridors. The ventilation must provide ducted, directional
airflow by drawing air into the lab from clean areas and with no recirculation (Fig. 5).

5.1.4 Biosafety level 4

The maximum containment laboratory — Biosafety Level 4 is designed for work with
Risk Group 4 microorganisms. Before such a laboratory is constructed and put into
operation, intensive consultations should be held with institutions that have had ex-
perience of operating a similar facility. Operational maximum containment laborato-
ries — Biosafety Level 4 should be under the control of national or other appropriate
health authorities (Fig. 6).

Agents requiring BSL 4 facilities and practices are extremely dangerous and pose
a high risk of life-threatening disease. Examples are the Ebola virus, the Lassa virus,
and any agent with unknown risks of pathogenicity and transmission. ‘These facilities
provide the maximum protection and containment. To the BSL 3 practices, we add
requirements for complete clothing change before entry, a shower on exit and decon-
tamination of all materials prior to leaving the facility.

16 Sreenivas Reddy Bathula & A. Rakhimol / BioRisk 12: 1-23 (2017)

Figure 6. Biosafety level 4 laboratory.

The BSL 4 laboratory should contain a Class II biological safety cabinet but
may use a Class I or II BSC in combination with a positive-pressure, air-supplied
full-body suit. Usually, BSL 4 laboratories are in separate buildings or a totally iso-
lated zone with dedicated supply and exhaust ventilation. Exhaust streams are fil-
tered through high-efficiency particulate air (HEPA) filters, depending on the agents
used. Along with those such as impervious, easy-to-clean surfaces, insect and rodent
control, and total barrier sealing of all wall, floor and ceiling penetrations has to be
paid attention.

5.2 Facility commissioning

Laboratory/facility commissioning may be defined as the systematic review and docu-
mentation process signifying that specified laboratory structural components, systems
and/or system components have been installed, inspected, functionally tested and veri-
fied to meet national or international standards, as appropriate. The respective build-
ing system's design criteria and design function establish these requirements. In other
words, laboratories designated as Biosafety Levels 1-4 will have different and increas-
ingly complex commissioning requirements. Geographical and climatic conditions, such
as geological fault lines or extreme heat, cold or humidity may also affect the labora-
tory design and therefore the commissioning requirements. Upon the completion of the
commissioning process, the pertinent structural components and support systems will
have been subjected to the various operating conditions and failure modes that can be
reasonably expected, and will have been approved. The commissioning process and ac-
ceptance criteria should be established early, preferably during the programming phase

Global Trends in Biorisk Management 7

of the construction or renovation project. By acknowledging the commissioning process
early in the project, architects, engineers, safety and health personnel and ultimately
the laboratory occupants understand the performance requirements of the specific lab-
oratory and set uniform expectations for laboratory and/or facility performance. ‘The
commissioning process provides the institution and the surrounding community with
a greater degree of confidence that the structural, electrical, mechanical and plumbing
systems, containment and decontamination systems, and security and alarm systems will
operate as designed, to assure containment of any potentially dangerous microorganisms
being worked with in a particular laboratory or animal facility. Commissioning activities
generally begin during the programming phase of the project and proceed through the
construction and subsequent warranty period for the laboratory/facility. Warranty peri-
ods should generally extend for one year following occupancy. It is recommended that
a commissioning agent is retained who is independent of the architectural, engineering
and construction firms involved in the design and construction. The commissioning
agent serves as an advocate for the institution constructing or renovating the laboratory
and should be considered as a member of the design team; involvement of the agent
in the early programming phase of the project is essential. In some cases, the institu-
tion may act as its own commissioning agent. In the case of more complex laboratory
facilities (Biosafety Levels 3 or 4), the institution may wish to retain an outside commis-
sioning agent who has demonstrated experience and success in the commissioning of
complex biosafety laboratory and animal facilities. When an independent commission-
ing agent is used, the institution should still be a member of the commissioning team.

5.3. Facility certification

The laboratory biorisk management standard CWA 15793, which is based on a man-
agement system approach like ISO 9001, ISO 14001 or OHSAS 18001, is intended
to help laboratories develop a systematic framework for managing their risks. First, it
requires a policy statement, which puts forth a strategic positioning and a formal com-
mitment from the organization’s top management. Secondly, biosecurity is included
in the whole risk management approach together with biosafety. Last but not least,
the planning phase is not limited to the risk assessment, but also includes planning
for the resources needed for the implementation of the decisions and the monitoring
of their outcome, which appears as some guarantee for a sustainable management.
In general, key features of all management systems include structuring the system to
achieve the organization's objectives in the most effective and efficient way, under-
standing the interdependencies between the processes of the system, structuring ap-
proaches to harmonize and integrate processes, providing a better understanding of
the roles and responsibilities necessary for achieving common objectives (and reduc-
ing cross-functional barriers), understanding organizational capabilities and establish-
ing resource constraints prior to action, targeting and defining how specific activities
within a system should operate, and continually improving the system through meas-

18 Sreenivas Reddy Bathula & A. Rakhimol / BioRisk 12: 1-23 (2017)

urement and evaluation. All of these management system elements are applicable to
managing laboratory biorisks and their implementation can be enhanced through a
risk governance framework.

6. Safety organization and training

It is essential that each laboratory organization has a comprehensive safety policy, a
safety manual, and supporting programmes for their implementation. The responsi-
bility for this normally rests with the director or head of the institute or laboratory,
who may delegate certain duties to a biosafety officer or other appropriate personnel.
Laboratory safety is also the responsibility of all supervisors and laboratory employees,
and individual workers are responsible for their own safety and that of their colleagues.
Employees are expected to perform their work safely and should report any unsafe acts,
conditions or incidents to their supervisor. Periodic safety audits by internal or external
personnel are desirable (Rodney K. Wilson 2015).

6.1 Biosafety officer
Wherever possible a biosafety officer should be appointed to ensure that biosafety poli-

cies and programmes are followed consistently throughout the laboratory. ‘The biosafe-
ty officer executes these duties on behalf of the head of the institute or laboratory. In
small units, the biosafety officer may be a microbiologist or a member of the technical
staff, who may perform these duties on a defined part-time basis. Whatever the de-
gree of involvement in biosafety, the person designated should possess the professional
competence necessary to suggest, review and approve specific activities that follow ap-
propriate biocontainment and biosafety procedures. The biosafety officer should apply
relevant national and international rules, regulations and guidelines, as well as assist the
laboratory in developing standard operating procedures. The person appointed must
have a technical background in microbiology, biochemistry and basic physical and bio-
logical sciences. Knowledge of laboratory and clinical practices and safety, including
containment equipment, and engineering principles relevant to the design, operation
and maintenance of facilities is highly desirable. The biosafety officer should also be
able to communicate effectively with administrative, technical and support personnel.

6.2 Biosafety committee

Biosafety committee a biosafety committee should be constituted to develop institu-
tional biosafety policies and codes of practice. The biosafety committee should also
review research protocols for work involving infectious agents, animal use, recombi-
nant DNA and genetically modified materials. Other functions of the committee may

Global Trends in Biorisk Management 19

include risk assessments, formulation of new safety policies and arbitration in disputes
over safety matters. The membership of the biosafety committee should reflect the
diverse occupational areas of the organization as well as its scientific expertise (https://
bch.cbd.int/database/attachment/?id=10858). The composition of a basic biosafety
committee may include:

e Biosafety officer(s)

e Scientists

¢ Medical personnel

e Veterinarian(s) (if work with animals is conducted)
e Representatives of technical staff

e Representatives of laboratory management.

The biosafety committee should seek advice from different departmental and special-
ist safety officers (e.g. with expertise in radiation protection, industrial safety, fire preven-
tion, etc.) and may at times require assistance from independent experts in various associ-
ated fields, local authorities and national regulatory bodies. Community members may
also be helpful if there is a particularly contentious or sensitive protocol under discussion.

7. Organizations Monitoring Biorisk

7.1 World Health Organization (WHO)

http://www.who.int/csr/bioriskreduction

The WHO has at least two sets of relevant activities: the Biosafety and Laboratory
Biosecurity Programme; and the project of the biorisk reduction for dangerous patho-
gens team on life science research and development for global health security.

The WHO Biosafety and Laboratory Biosecurity programme is designed to as-
sist member states understand, adopt and implement biorisk management strategies
to minimize risks of infections through safe and secure practices in laboratory and
transport environments, and to accomplish these goals in a cost-effective manner. It
is part of WHO’s efforts to establish a biosafety and laboratory biosecurity culture
worldwide. To this end, the programme provides guidance on, and promotes the use
of, safe and secure workplace practices, appropriate protective equipment, engineering
and administrative controls in the handling of pathogenic organisms in laboratories,
during transportation, in field investigations and in vaccine manufacturing facilities,
to protect workers, the environment and the community from exposure, infection, and
subsequent development of disease. Five WHO biosafety collaborating centres support
the Global Biosafety and Laboratory Biosecurity Programme. They each have nomi-
nated a focal point to be a member of the WHO Biosafety Advisory Group (BAG) to
support the programme. The BAG meets regularly to address outstanding biosafety
and laboratory biosecurity issues, to discuss activities, projects and collaborations.

20 Sreenivas Reddy Bathula & A. Rakhimol / BioRisk 12: 1-23 (2017)

7.2 Food and Agriculture Organization (FAO)
http://www.fao.org/biosecurity

The activities of FAO are not so obviously linked to the topics under discussion at
the Biological Weapons Convention (BWC) meeting of experts. Nevertheless, certain
elements, especially as they relate to the development of biosafety best practices, are
closely related; others contain resources which could be extrapolated to fit the BWC
context, such as principles of capacity building in disease-related fields. The FAO has
conducted a technical consultation on biological risk management in food and agri-
culture in Thailand in 2003; created an international portal on food safety, animal and
plant health; established a Working Group on Biosafety; detailed examples of national
approaches to biosecurity; conducts a capacity building programme; and has reviewed
certain thematic areas, including biotechnology in food and agriculture, biotechnology

and food safety, and animal and plant health.

7.3 World Organization for Animal Health (OTE)

http://www.oie.int

The OIE collaborates with other international organisations on the development of ge-
neric biosafety and safe transport guidance, the OIE produces a number of key docu-
ments specifically targeting animal-related fields. The OIE produces the international
health standards for animals and animal products — trade standards and biological
standards: the Terrestrial Animal Health Code; the Manual of Diagnostic Tests and
Vaccines for Terrestrial Animals; the Aquatic Animal Health Code; and the Manual of
Diagnostic Tests for Aquatic Animals. These standards deal with a range of pertinent is-
sues: risk management approaches and principles; biosecurity consideration (especially
in the animal and agricultural use of the term); identification and traceability of live
animals; hygiene precautions; and disinfection and disinsectisation.

The OIE also produces a number of other resources. The OIE Quality Standard and
Guidelines for Veterinary Laboratories: Infectious Diseases sets out the management and
technical competence for the accreditation of testing for infectious animal disease. ‘This
quality control system contributes to ensuring the safe and secure operation of relevant
facilities. The standards cover: management requirements (including quality systems,
document control, records, internal audits and management reviews); technical require-
ments (including personnel issues, equipment, measurement traceability and handling
of specimens); validation of laboratory techniques; and international reference standards.

8. Conclusion

Some of the most worrisome incidents happen in laboratory due to overlooking of
safety rules and not following the guidelines given by Instructors/ safety trainers. Bad

Global Trends in Biorisk Management 24

handling of instruments and chemicals without reading safety guidelines, misusing
them for alternate purposes could cause devastation. Wearing protections and taking
safety measures like how to use first aid kit, safety equipment, know the locations of
the fire extinguishers, eyewash, and water taps is essential. Conducting experiments in
right environment like fume hood, safety cabins, handling chemical leftovers, poten-
tial pathogens in an appropriate manner, avoid self contaminating, keeping track of
harmful chemicals and strains is important. (https://wyss.harvard.edu/staticfiles/pdf/
WyssBiosafety Manual-July2012.pdf)

The biorisk management approach described is composed of a biosafety, a labora-
tory biosecurity and an ethical component. It offers laboratory facilities a programme
that should help them to protect their valuable scientific assets. Concurrently with
the work of other agencies and entities that have addressed biosecurity issues in a va-
riety of contexts and from other viewpoints, this document has addressed VBM and
the growing advances in life sciences and related technologies that are likely to alter
the spectrum of current and future biorisks, presenting ways to identify, prevent and
minimize them. Under the ultimate responsibility of laboratory directors whose tasks
should include the ability to demonstrate that risks are appropriately managed, biorisk
management programmes may be divided into seven main components:

1. Identify VBM that require protection on the basis of regularly performed bi-
orisk assessments.

2. Establish clear guidance, roles, responsibilities and authorities for those who
work with or have access to VBM and to the facilities that contain them.

3. Promote a culture of awareness, shared sense of responsibility, ethics, and re-
spect of codes of conduct within the international life science community.

4, Develop policies that do not hinder the efficient sharing of reference materials

and scientific data, clinical and epidemiological specimens and related infor-

mation, and that do not impede the conduct of legitimate research.

Strengthen collaboration between the scientific, technical and security sectors.

coast

Provide appropriate training to employees of laboratory facilities.

7. Strengthen emergency response and recovery plans on the assumption that
biorisk management systems can only minimize, but never really eliminate,
every conceivable threat.

The threat of chemical weapons or malicious use of chemicals was always there,
along with that by using advances in biotechnology microorganisms can be created
against humans, livestock, crops, food, water infrastructure and other economically
valuable entities (Smith et al. 2017). It is important to create a biorisk checklist to
make the people aware of biohazard materials (Naroeni et al. 2016). In order to imple-
ment technologies at the laboratory working level, a management team should be cre-
ated whose role is to protect workers, the environment, the product and the biological
pathogen. To face the increasing biological threat from emerging infectious diseases
and bioterrorism, it has become essential for governments around the globe to increase
awareness and preparedness for identifying and containing those agents (Zaki 2010).

22 Sreenivas Reddy Bathula & A. Rakhimol / BioRisk 12: 1-23 (2017)

National and international monitoring authorities should prevent the proliferation
and the use of chemical, biological, radiological, and nuclear (CBRN) weapons (Al
Jewari and Koblentz 2016). It is urgent to realize the concept of biological risk assess-
ment and management on handling pathogenic biological agents (PBA). The develop-
ment of a methodology to assess laboratory biological risks assures the handling of PBA
(Dobrokhotskif and Kolombet 2010). Russia and many European Union countries
were implemented international standards (CWA 15793:2008, CWA 15793:2011)
in laboratory biorisk management (Dobrokhotskii and Diatlov 2013, Sundqvist et
al. 2013, Dobrokhotskii et al. 2012). In developing countries awareness programs are
necessary on biosafety/ biosecurity/ biocontainments. Technology transfer is crucial to
achieve sustained scientific growth and build cooperation between countries. Programs
such as seminars, conferences, workshops, policy documents related to biorisk man-
agement in biomedical and biotechnology laboratories are needed to create awareness
among scientists (Khan et al. 2016).

Furthermore, the commitment to constantly improve biorisk management per-
formance for a facility and its operation through attainable goal-setting and actual
goal-achieving should be encouraged and acknowledged at all levels. Ethical, legal and
economic framework conditions changes from country to country (Hamill 2017). The
World Health Organization has recognized the importance of Human genetic vari-
ation both within and among population. The levels of biosafety standards differ as
biological-risk assessment varies (Reymond et al. 2002).

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