Laboratory Information Management System For Biosafety Laboratory: Safety and Efficiency
Laboratory Information Management System For Biosafety Laboratory: Safety and Efficiency
Laboratory Information Management System For Biosafety Laboratory: Safety and Efficiency
net/publication/351827389
CITATIONS READS
0 70
3 authors, including:
Some of the authors of this publication are also working on these related projects:
All content following this page was uploaded by Dingzhong Andrew Sun on 25 May 2021.
Review Article
a r t i c l e i n f o a b s t r a c t
Article history: Laboratory information management system (LIMS) has been widely used to facilitate laboratory activ-
Received 15 September 2020 ities. However, the current LIMSs do not contain functions to improve the safety of laboratory work,
Received in revised form 25 February 2021 which is the major concern of biosafety laboratories (BSLs). With tons of biosafety information that need
Accepted 9 March 2021
to be managed and an increasing number of biosafety-related research projects under way, it is worthy of
expanding the current framework of LIMS and building a system that is more suitable for BSL usage. Such
a system should carefully trade off between the safety and efficiency of regular lab activities, allowing the
Keywords:
laboratory staff to conduct their research as free as possible while ensuring their and the environment’s
Laboratory information management
system
safety. In order to achieve this goal, the information on the research contents, laboratory personnel,
Biosafety experimental materials and experimental equipment need to be well collected and fully utilized by a cen-
Biological research laboratory tralized system and its databases.
Laboratory safety Ó 2021 Published by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article
Workflow management under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2. Laboratory Information Management System for Biosafety Laboratory (BSL-LIMS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.1. Project management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
2.1.1. The safety modules for project preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
2.1.2. The safety modules for On-Going project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
2.2. Personnel administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2.3. Experimental materials management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
2.4. Equipment management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3. Beyond the basics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Declaration of Competing Interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
1. Introduction gram robots (for example, the Biomek series from Beckman Coul-
ter) to execute iterative experiments without any human
Laboratory information management system (LIMS) is a com- operation.5 Outside the lab, many current LIMSs in clinical and
puterized system that collects, processes and stores laboratory- analytical labs have greatly accelerated the process to present
generated information. Though, initially, the LIMS was simply the test results to the customers/testees because of a network-
invented for automation of experimental data, it now has the based reporting system.4 For whatever functions a LIMS actually
potential to develop into the digital hub of many laboratory activ- possesses, the purpose of the LIMS is to save human labor, and
ities.1–4 Inside the lab, by deeply entwining the LIMS and highly- improve data quality (i.e. accuracy, reliability and timeliness).6
automated laboratory equipment, researchers are even able to pro- Although the importance of LIMS in a lab was quite low at the
beginning, with the rapid development of computer and network
technologies, the LIMS had gradually evolved to play more diverse
⇑ Corresponding author.
roles and become an irreplaceable part in many labs. The range of
E-mail address: [email protected] (L. Wu).
https://doi.org/10.1016/j.jobb.2021.03.001
2588-9338/Ó 2021 Published by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
D. Sun, L. Wu and G. Fan Journal of Biosafety and Biosecurity 3 (2021) 28–34
the users of LIMS has expanded as well, from mostly analytical high level biosafety labs (BSL-3 or -4), or basic research BSLs.
labs, to diagnostic biosafety laboratories (BSLs) of specific function Since BSL-LIMS has its root in BSLs, the focus of the system is
and many general research labs.2,3,7,8 different from the traditional LIMS as how BSLs are different
Nevertheless, the functions of all the current LIMSs to our from regular research labs. Biosafety and biosecurity are
knowledge do not touch the major concern, i.e. biological safety brought up to the front as main concerns in BSL-LIMS with sim-
and security, of biosafety labs. This is even true for those LIMSs ilar, if not more, importance as efficiency.10 Biosafety in labora-
being currently used in BSLs. Although, through the depletion tories includes two parts: 1) the safety of people who work in
and reduction of human factors from certain experimental sec- the lab or are related to the laboratory personnel; 2) the safety
tions, the current LIMSs have actually increased the general safety of environment.11 So the aim of BSLs is to keep both the per-
of the BSLs, these systems themselves do not contain any safety- sonnel and environment safe before, during, and after the
and security-control mechanisms. The focus of a traditional LIMS, experiments. If there are any unavoidable safety risks in the
whether it is used in BSLs or not, is still to better facilitate lab staff course of a research project, then the risks must be reduced
doing experiments. Even the Electronic Laboratory Notebook to an acceptable and controllable degree before the start of
(ELN), a function widely appreciated by BSL staff, was not designed the project, and be kept this way until the end of it; otherwise,
for but merely happened to suit the working environment of BSLs. the project should be abandoned rather than allowed to begin.
Thus it is a matter of fact that we do not currently have any digital Hence, as a part of BSLs, the design of the LIMS has to comply
system that can help us manage the biosafety information. Mean- with the safety standards set by the BSLs. Since biosafety is a
while, tons of biosafety-related information are being collected, precondition for experiments in BSLs, the focus of the corre-
stored and transmitted in digital form since 2000, and there is sponding LIMS shifts from the post-experimental information
actually much more digitalized biosafety information than any (i.e. results) management to the pre-experimental information
other kind of safety information.9 Together, those result in a very (i.e. preparation) management. Even though the overall frame-
strange situation: while biosafety information itself is highly digi- work of BSL-LIMS might look similar to the one of traditional
talized, there is no centralized system in control to organize the LIMS, the contents of them would be very different.
electronic information altogether and to use it appropriately. Every The information management in a BSL can be divided into four
piece of information usually stays in the form of isolated electronic categories:
documents in either a local computer or on a local network, and
the search and retrieval of the information are usually complicated. 1. Project management
For example, when a safety document/form/sheet is requested by a 2. Personnel administration
user, the calling, deployment, and returning of the document is 3. Experimental material management
mostly done separately by humans, via a not-well-indexed infor- 4. Equipment management
mation system and certain unrelated transmission system like
email or even paper-based messaging. Hence, the information The whole information management system would involve
management system in biosafety labs, if they do exist, is ineffec- large amount of information collection and exchanging within
tive, inefficient and cannot satisfy the needs of biosafety labs. and between different categories. And many check points need
Therefore, we believe that a specific information management sys- to be set up for the sake of safety control. These interconnected
tem for biosafety laboratories that is able to improve the safety and information flows and check points form an elaborate network
efficiency of these laboratories is a necessity. whose structure can be simplified to Petri Nets,2 with laboratory
data or information as places, and research or audit activities as
2. Laboratory Information Management System for Biosafety transitions. Since the laboratory work flow management has
Laboratory (BSL-LIMS) already been a part of many regular research labs’ information
management systems(2, 3, 7), some modules in these traditional
The laboratory information management system for biosafety LIMSs (e.g. the management of samples, materials, or equip-
laboratory (or BSL-LIMS in abbreviation) proposed in this paper ment) may be used by the BSL-LIMSs, though new databases
is an information management system specifically designed for on biosafety information should be added and the some struc-
29
D. Sun, L. Wu and G. Fan Journal of Biosafety and Biosecurity 3 (2021) 28–34
tures probably need to be redesigned in order to meet the new Secondly, in regular biological labs, the lab director or other
demands for biosafety and biosecurity. person who is in charge may do an inspection of the experi-
menters, the experiment materials, and the experiment equipment
2.1. Project management and facilities at the beginning of the project. However, this kind of
inspection is mostly voluntary and very coarse, and the inspected
Research projects comprise the body of a research laboratory. In contents are usually arbitrary. There is no mechanism to secure
other words, a research lab is founded so as to support one after the compliance with certain operation rules before and during
another research project. Hence, the effective management of pro- the project, since it lacks nationally or institutionally enforced laws
jects is the most important job for a lab manager or director. How- or regulations. As a result, few lab workers and principal investiga-
ever, there are two new challenges to meet to get the job done in tors would attempt to make sure that everything that would be
high level BSLs, in addition to the challenges raised in regular involved in the project is well prepared before they start the first
laboratories. experiment; instead, more would try to get started first as soon
First, the high level BSLs are usually multi-purpose research lab- as the basic conditions of the project has been met, and the com-
oratories that do diverse studies. Unlike the diagnostic or analytical plete fulfilment of the experimental conditions would be consid-
laboratories, whose type of work is usually the same all the time, ered to be a parallel task. This mode might work in some of the
the projects within a research lab are usually changing from time regular research labs, but should be avoided by every BSL.
to time. In a diagnostic or analytical laboratory, LIMS can be In regular biological labs, since the contagious materials or
adopted to manage the lab activities once the diagnostic or analyt- other self-propagating materials of potential danger (e.g. gene
ical process has been determined.4 Since the information flows in drive materials) are excluded from experiments, the causes of acci-
these laboratories usually follow a linear structure, once the LIMS dents are usually non-biological factors. These factors may lead to
has been installed and connected with automated devices, it can very serious consequences, but the range of their influence is
then take its role as the information hub and quality control center mostly limited to the lab itself and its workers. For instance, cen-
of the laboratory.6 In contrast, the BSLs or general research labs trifugation is one of the common causes in laboratories that can
change their experimental contents comparatively often, and lead to severe injuries or even death of people.12 Nonetheless,
therefore no single procedure is enough to keep the laboratory the damage caused by centrifuge failure can hardly go beyond
activities safe and successful. As a result, the LIMS would be down- the neighboring rooms where the centrifuge locates and usually
played to be an ELN or a data reporter attached to certain piece of only has short-term detrimental effect. In contrast, the leakage of
automated equipment,2,8 losing its central position as the informa- untreated contagious materials from BSLs can lead to massive
tion hub of the lab, unless we can expand its functions.7 infection far beyond the laboratory workers and last as long as
Fortunately, the new functions to make a LIMS adapt to the BSL the chain of transmission has not been broken. Even a leakage from
usage are not difficult to achieve. All we need to do is to step back a a teaching lab of low biosafety level may cause infection in a large
bit and take a look at the whole picture. From a principal investi- community.13 Hence, the BSLs need extra safety measures to coun-
gator’s point of view, all research activities follow certain pattern ter the increased risk and lower the rate of accidents, especially the
(Fig. 1.). If we can expand the audit and revision control, which infection accidents, to the minimum (Fig. 2.). However, there are
are the core functions in the LIMS, from of only ‘‘scientific data” several prizes for doing so. First, adding extra authorization and
to of all ‘‘data that could affect scientific research”, then we should inspection processes will cost scientists extra time. The increase
be able to create a system that is able to oversee all research pro- in the time that they have to spend on non-research affairs will
jects in a laboratory. Each of these projects contains three aspects lower their efficiency and subsequently reduce the projects’ out-
to be managed: the experimenters, the experiment materials, and put. Second, humans are prone to errors and thereby can make
the experiment equipment and facilities. All of these aspects are more mistakes when being more burdened. Although the aim of
affected by the contents of the specific project, and the quality of extra safety regulations/rules is to lower the risk, the increased
preparation for these aspects will predetermine whether the pro- amount of precautions also adds the burden on both research staff
ject will go well or not. and biosafety managing staff, making them easier to get exhausted
30
D. Sun, L. Wu and G. Fan Journal of Biosafety and Biosecurity 3 (2021) 28–34
by the extra safety information that they need to deal with. The and biosafety officers can only make sensible judgement on the
reduced mental and physical state is often a cause of laboratory project if they know enough about the type of danger that a
accidents.14 Therefore, we need a tireless worker to facilitate microbe poses and its causing mechanism.23 For the microbes
humans, lowering the work load and errors of humans’. And that whose risks are unknown, the maximum containment laboratory
is exactly what a BSL-LIMS can offer. (BLS-4) should be used, and some operations that could increase
Because the work flows in a research BSL (Fig. 2.) are similar to the potential risk should be avoided. The BSL-LIMS should also con-
the ones in a regular multi-purpose biological laboratory (Fig. 1), tain a reporting function, maybe mandated by national laws, that
only with some additional safety check points, the BSL-LIMS can can allow individual users to report infectious incidents or newly
refer to some well-recognized standards (e.g. the International discovered biological risks. Only then the national databases of bio-
Organization for Standardization (ISO) and Clinical & Labs Stan- logical risks can effectively collect new biosafety information, be
dards Institute (CLSI)) and/or previous studies2–4,7,15 to design continuously updated and provide support to labs in a large area.24
the modules that are in common to all the biological labs (e.g. Theoretically, the national database on dangerous microbes should
project-template making, the experiment scheduling, sample man- be open to as many researchers as possible through internet, thus
agement, experimental data collection, results analysis and report- everyone related could utilize and contribute to the system. How-
ing, etc.). In contrast, for the processes that are unique to the BSLs, ever, due to the serious consequences that could be caused by the
there is no previous standard or study that can be used as exam- malicious use of this information, every country or region should
ples. Thus, we have to create new modules or update existing LIMS decide which open level is most appropriate based on their own
modules to satisfy the requirements of safety information manage- security situation.
ment, based on institutional, national or international biosafety b. Technical and methodological information database. The
guidelines.11,16,17 The project management can be divided into infection of a human being is a complex process. It is not only con-
two parts based on their effective stage: cerns the infectious dose (e.g. ID50), but also the state of the con-
tagious material (e.g. DNA or RNA, inactivated strain, genetically
2.1.1. The safety modules for project preparation modified strain, etc.), and the actual dose of exposure.11,25 Hence,
After a project proposal has been reviewed and passed by the the actual level of risk can only be assessed after considering both
relevant committee(s), and got funded, the researchers have to the pathogenicity of the microbe and the experimental methods.
turn the contents that they outlined in the proposal into a more The final risk level of an experiment can be higher or lower than
detailed and feasible plan. To manage different types of research the risk level of the pathogen, depending on the specific experi-
activities, the LIMS has to be highly flexible and support user con- mental method that will be used. A well-indexed technical and
figuration; to limit the complexity of such a LIMS, the system need methodological information database powered by a search engine
to be modularized with customizable modules or reusable tem- can be used as a reference system when the researchers are prepar-
plates.7,18 If this is a project that requires BSL usage, then the rele- ing the protocols. And once they submit it to the laboratory manag-
vant biosafety databases and safeguard mechanisms are necessary ing staff, a word processor can compare the keywords in the
as well. Since most of the laboratory texts nowadays are stored in database to what it finds in the context, automatically highlighting
digital form, it is possible to automatic recognize and extract some or warning the reviewers about the parts that may change the risk
biosafety related information (e.g. certain words, phrases, etc.) level.
within the texts via using special word processers and relevant c. Laboratory staff information database. Laboratory staff can be
databases. The reviewers or biosafety officers can use the extracted divided into three main categories based on their duties or types of
information to classify the research projects before giving any fur- work: the research staff, the biosafety staff, and the logistic staff.
ther examination; or, if the laboratory texts are all standardized Each can be subdivided furthermore based on their skills, positions
and machine-validated, the computer may be able to do the classi- or qualifications. A database that contain position, health, reliabil-
fication instead of humans, and/or directly warn the researchers ity and skill information on laboratory staff is essential for labora-
about the flaws of their research plan when they try to submit tory management. The details of this part will be discussed in
it.7 In this module, the biosafety information databases are the section 2.
cornerstones that determine the upper limit of data automation, d. Experimental material information database. A project usu-
though the algorithms also matter. The specific set of databases ally consumes a large amount of experimental materials. Sufficient
that are linked to a BSL-LIMS will be determined by the need of and high-quality materials are not only the assurance of a success-
the BSL and its research contents, but the types of databases may ful study but also one of the preconditions for laboratory safety.
be more or less the same in all BSLs. The details of how to manage this information will be covered in
a. Microbial information database. The biosafety information on section 3.
the microbes, especially pathogens, that will be involved in the e. Equipment information database. Equipment is able to pro-
project directly determines the biosafety level that is required to tect experimenters but can be a source of risk as well if being used
undertake the project. In terms of pathogenic microorganisms, inappropriately. We will discuss how to manage its information to
many countries have established their own pathogen information improve the safety during equipment usage in section 4.
databases to guide the related studies,19,20 while a few have made
legal policies to regulate non-pathogenic organisms of potential 2.1.2. The safety modules for On-Going project
danger as well.21,22 Labs and institutions should keep good aware- Everything, including human beings, that exits a biosafety lab
ness to the local/regional/national biosafety guidelines or policies, may contain biohazards. To protect the lab workers and the envi-
and follow these guidelines and policies all the time. Therefore, ronment, standard operating procedures (SOPs) and safety guideli-
whenever such governmental databases exist, labs and institutions nes should be followed when experimenters are working.
should always refer to them if they need to build their own micro- Nonetheless, humans are error-prone and always have a propen-
bial information databases. These databases will help laboratory sity to explore the safety margin in the system to improve effi-
staff to assess the potential risk of certain project and provide sug- ciency, due to all kinds of pressures.26 As a result, a safety
gestion on whether and how to undertake it. For all known patho- control mechanism for on-going projects in BSLs is required to pre-
gens or other type of dangerous microbes, the database should vent incidents from occurring or being exacerbated. The mecha-
include as much information on their pathogenicity or other nism usually includes at least an electronic surveillance and
potentially harmful mechanisms as possible. The research staff detection system, a building automation system with sites that
31
D. Sun, L. Wu and G. Fan Journal of Biosafety and Biosecurity 3 (2021) 28–34
can be remotely controlled, and a health surveillance program for might be one of the most effective methods to tell the identities of
all lab staff. Currently, the lab safety staff’s stewardship is the only experimenters. For example, every experimenter would be
additional force to safeguard on-going projects. Once the research assigned a specific color of his/her own. He/she will always wear
staff have started an experiment, they have to rely on their own the caps or gowns in this color in the lab. With the information pre-
good safety practice to keep everything on the right track. The recorded in a database, his/her identity can be easily confirmed
safety officers may frequently monitor the operations of experi- automatically when the color is captured by a video camera. Nev-
menters’, but only communicate with them when they sense a ertheless, the modules described above merely provide a tracking
major risk. In addition, since the focus of experimenters is often system that is good for record keeping but will depend on the vig-
not on safety, and the safety staff could not be in the working area ilance of safety staff to perceive abnormal behaviors and prevent
and monitor every single move of the experimenters, there would accidents. From this point of view, the movement tracking system
be a lag between the occurrence of a risk and the human detection is only the first step towards a real automatic accident preventive
of it. This reality calls for a better safety warning mechanism that is system.27 In the future, digital indicators and input terminals
capable of prevention and early detection of incidents. should be encompassed into the system together with the proxim-
Automatically-triggered alarms have been widely used in ity detectors. Since the indicators and input terminals installed at
devices with physical or chemical safety thresholds. The alarms specific control sites, such as the centrifuges and exits, will auto-
or likewise warning devices can warn the related laboratory staff matically react to experimenters’ approach and showing them nec-
promptly as soon as a potential risk is detected. Thus the lab staff essary information, experimenters will be able to receive guidance
would have enough time to react and prevent accidents from on their protocol and input data from anywhere in the lab. And the
occurring or limit the damage of them. However, most biological overall safety of the lab should be improved.
incidents are not caused by a single event,26 and biological risks
usually lack threshold values23 (as discussed in 1.1). Therefore, this 2.2. Personnel administration
warning mechanism based on continuous monitoring of certain
thresholds (e.g. the room pressure, chemical concentration in a Human workers are at the center of all stages of scientific
closed area, direction of airflow, etc) are not good enough maintain research activities. They are the main target that we want to pro-
the overall safety of BSLs. For the risks caused by complex biolog- tect but also a major cause of incidents in biosafety labs.14,25 The
ical operations, this system can do little help. laboratory staff, especially those who work with pathogens, has a
A more practical safeguarding mechanism for biohazardous much higher rate of acquiring certain infectious diseases compar-
control would be a node-based system, in which the experimental ing with ordinary people.28 Therefore, the effective and efficient
information will be assembled and submitted to the control node, administration of laboratory staff is one of the essential part to
and machines and/or humans will analyze the information and maintain biological safety and security in and outside BSLs.
decide if the next action is safe to be taken. Although LIMSs used Distinguished by their roles in biosafety laboratories, the per-
in both of the diagnostic/analytical labs and research labs have sonnel can be generally divided into three categories:
some quality control mechanism to prevent invalid inputs into a. The research staff. People in this group are the true users of
the next node,4,7 they are still operated in linear workflow and the laboratory. They are in the majority of laboratory staff, but
dealing with single-source data validation. Moreover, since the their population composition would change dynamically because
LIMSs are built for linear processes, the results of validation would many of them may be students. Since they are frequently in close
only go back to the experimenters. The BSLs demands the LIMS to contact with contagious materials, the safety and health conditions
be able to validate results from multiple sources as well as notify of these people must be examined as often and as rigorously as
the safety staff about any sign of risks. Therefore, the control node possible.23,29 The information on research staff’s skill level and
in BSL-LIMS should be able to automatically validate results from health condition (which includes both physical and mental health
different sources and synthesize the results, and instantly notify conditions) should be stored in a database whose contents can be
both experimenters and safety staff about any anomaly. called by the BSL-LIMS. The database need to be updated fre-
Contagious materials and lab workers are the major focuses in quently, not only by biosafety officers or BSL directors but by
biosafety control. As a result, the continuous tracking of their human resource staff and the research staff themselves as well.
movement would help improve the general safety of the lab or The medical history should be attached to the person’s other infor-
get investigators a better hindsight in accident analysis. For these mation for lab managing staff to review. Adjustments must be
reasons, the safety module of BSL-LIMS should be connected with made when something suggests a person will not be suitable for
certain proximity detectors as well. These detectors are able to the current job any longer, which applies to BSL staff in other cat-
monitor human behaviors and/or the movement of important bio- egories as well. The BSL-LIMS should warn the person in charge
logical samples. Since most accidents occur during the interaction when a change in staff information has been made. The alarm will
between the lab workers and the contagious materials, operations not be turned off until the issue is resolved, which resembles the
involving such kind of interactions deserves special attention and issue submission system in many online custom support systems.
should be monitored as much as possible. The tracking of samples In general, the valid period and access level of an authorization for
can be realized by physical tagging their containers with whatever a research staff are determined by the contents and period of his/
method that can be turned into electronic signals. For example, sci- her project.
entists have successfully used Radio Frequency Identification b. The biosafety managing staff. The number of biosafety staff is
(RFID) for item tracking in chemical laboratories.27 The continuous usually quite small compared with the number of research staff,
tracking of humans is more complicated but not impossible. Due to but their importance need not be emphasized more. As the over-
the health concern and large size of human beings’, the signal gen- seers of the BSLs, they are the last line of defense against laboratory
erated by an attached emitter need to be safe for human body but accidents. All the safety officers who work for BSLs that are above
strong enough to be read by a receiver. An alternative method is to safety level 2 need (usually state) admitted qualifications, showing
give experimenters visual labels that can be recognized by a recog- they have received enough training to direct BSLs of that level. The
nition system through cameras. Though direct biometric recogni- directors, and sometimes technicians, may be the only safety offi-
tion is difficult in BSLs due to the body coverage by personal cers in basic BSLs (BSL-1 and BSL-2), whilst the containment labs
protective equipment (PPE), experimenters can be distinguished (BSL-3 and BSL-4) demand a specific team to take care of biosafety
indirectly by pre-designated visual labels. A color labelling system matters. Biosafety managing staff are usually permanent employ-
32
D. Sun, L. Wu and G. Fan Journal of Biosafety and Biosecurity 3 (2021) 28–34
ees of the institution. Theoretically, they have the highest authority can also put the experimenters at risk. For example, in 2011, a
when dealing with biosafety-related matters. Hence, their qualifi- major incident of laboratory-acquired infection (LAI) of Brucella
cation and reliability should be inspected periodically, ensuring spp. occurred in the Northeast Agriculture University, China, which
that they are trustworthy and able to rise to the new challenges. ended up with 28 people being infected.32,33 The incident was
c. The support staff. The support staff are responsible for the caused by multiple reasons, but the source of Brucella bacteria
periodical maintenance of the laboratory facilities, equipment was some uninspected goats used in dissection.
and the lab construction itself.11 They affect the extend of safety In order to reduce the problems caused by experimental mate-
and efficiency of a laboratory, even though they may not spend rials, it is important to set up strict rules on the purchase, storage
as much time in the lab as people in the other two categories. and usage of them.6 Though many commercial LIMSs have already
The administration of internal engineers and/or animal mainte- provided functions related to inventory management, the aim of
nance staff who are permanent or long-term employees of the such modules is to keep the supply chain in the lab uninterrupted.
institution will be similar to the administration of research staff. To fulfil the safety requirements of a BSL, the LIMS need to be
If the cleaning services need to be done by specific cleaning staff equipped with some safety control mechanism.
other than the research and biosafety staff, then it is important The upgraded module in BSL-LIMS will emphasize the quality
to ensure that they have the appropriate qualification, especially control of the experimental materials. Users’ purchase behavior
when they are responsible for the waste disposal/transportation. can be limited by enabling a white or black list of suppliers, and
The qualification and identity of external support staff should be relevant certifications or/and safety data sheet (SDS) should always
carefully examined by the safety officers and only perform their be provided and uploaded to the material information database.
job under the supervision of the safety officers. The laboratory staff should keep good records on all of the materi-
The personnel administration in BSLs requires the clarity of the als, having their quality indicators, e.g. current state, shelf life, suit-
laboratory jobs and detailed information on each current/potential able purpose etc., in the database. For the materials that could lead
worker. The access level to a lab is always depend on the person’s to major accidents, e.g. experimental animals or lysis buffers,34 the
position and specific job. The laboratory director can only recruit or local testing results and evidence of validity must be submitted to
assign the specific type of job to a lab worker if the recruit meets the biosafety officers and stored in the corresponding database
the specific requirements for that job. These requirements are usu- before further approval can be granted.
ally listed in the local and/or national laws and regulations, and Last but not least, the BSL-LIMS should have a tracking system
enhanced by the institution’s own rules.11,16,23 The training and of all biohazardous waste, including the information on the
authorization of most BSL staff follows a hierarchical structure method of decontamination, the disposal time, and at least one
where staff have to finish the training and work in a lower level emergency contact.
BSL for a period of time before they can be allowed to enter a
higher level BSL. This structure works for each categories of per-
2.4. Equipment management
sonnel. In addition to the professional skills and physical health,
increased attention has been called to the reliability and mental
The laboratory equipment can be divided into two categories
health of lab workers.10,14,30 Since biosafety and biosecurity are
according to their expected working period: the permanent or
never a standalone matter, the institutions with containment BSLs
long-term equipment (or facilities), e.g. centrifuges, biosafety cab-
should work with their local/national government to come up with
inets; dispensable equipment, e.g. personal protective equipment
a feasible reliability program in order to limit the risk that is
(PPE), disposable pipets and Petri dishes. Since dispensable equip-
brought by unsuitable job assignments.
ment are only good for one-time usage, which is similar to exper-
The BSL-LIMS will be able to help with the administration of
imental materials, their management can also refer to the
laboratory staff, especially the management of research staff,
management method of experimental materials. On the other
through automatic filtering their information. Since the BSL’s
hand, the long-term equipment needs to serve the lab for a period
access control firstly depends on the biosafety level of the lab,
of time and be used now and then. Hence, the equipment has to be
and then the contents of the specific project. A ‘‘machine-human”
well understood and well maintained for the laboratory’s safety.
cooperated process of access authorization can be established.
While the experimental materials have their SDSs to provide
Whenever an application for BSL usage has submitted, the com-
basic safety information on themselves, all pieces of lab equip-
puter will evaluate the appliers conditions first according to their
ment, including the dispensable ones, should also come with sim-
information in the database, comparing it with the requirements
ilar information. This information, along with the other biosafety
for using that BSL; then, the application will move to the managing
related information, will be provided to the research staff through
staff for further review if those requirements are satisfied, or it will
a client portal to the BSL-LIMS so that they will be able to learn
go back to the appliers with feedback on which condition(s) is/are
about which specific lab may satisfy their safety demands. The
not fulfilled. The system will repeat this process for a second time
maintenance information on lab equipment should also be
with refined requirements of the specific project. By using this
included into this database, and periodic maintenance alarm can
hybrid ‘‘machine-human” co-evaluation model, human labor will
be set up to remind the corresponding staff to maintain the equip-
be saved and human error can be reduced.
ment, or ban the usage of the equipment before it has been main-
tained. Besides, because of the busy schedule and special security
2.3. Experimental materials management
concern of containment BSLs, a maintenance schedule is always
very helpful for managing the laboratory activities, and an equip-
No research can be carried out without experimental materials,
ment information database that can be filtered by different condi-
though the improper use of experimental materials can pose major
tions will surely help to create such a schedule.
threat to the safety of experimenters and the environment. The
general principle of sample management in BSLs is to limit the
access to the contagious samples and keep a good record of its 3. Beyond the basics
usage,31 and more details have already been discussed in section
1.2. However, the contagious sample is not the only thing that The laboratory safety is a dynamic process that requires contin-
can inflict risks upon experimenters and environment. Other types uous inspection and updating rather than a once-for-all action.
of materials, including the experimental animals, with poor quality Laboratory directors and staff must be aware of that and adjust
33
D. Sun, L. Wu and G. Fan Journal of Biosafety and Biosecurity 3 (2021) 28–34
to any new challenges while maintaining a high level of alertness 10. Trevan T. Biological research: Rethink biosafety. Nature. 2015;527
(7577):155–158. https://doi.org/10.1038/527155A.
towards all the known risks. These challenges may come from
11. World Health Organization WHO; Laboratory Biosafety Manual. 2004.
newly discovered pathogens as well as the application of new tech- 12. Kolff J, Ankney RN, Wurzel D, et al. Centrifugal pump failures. J Extra Corpor
nologies (e.g. gene drive).22,35,36 The BSL-LIMS need to cope with Technol. 1996;28(3):118–122.
the changes in every aspect in a lab, thus the system must be easily 13. Emmert EAB. Biosafety tATCoL; biosafety guidelines for handling
microorganisms in the teaching laboratory: development and rationale. J
expandable. However, a highly expandable and flexible system is Microbiol Biol Educ. 2013;14(1):78–83. https://doi.org/10.1128/jmbe.v14i1.531.
frequently equal to a highly complex one, making every change 14. Wurtz N, Papa A, Hukic M, et al. Survey of laboratory-acquired infections
in the system unnecessarily time-consuming.18 How to trade off around the world in biosafety level 3 and 4 laboratories. Eur J Clin Microbiol
Infect Dis. 2016;35(8):1247–1258. https://doi.org/10.1007/s10096-016-2657-
between the flexibility and the complexity will be a challenging 1.
job for software engineers and product managers. In addition, 15. ASTM; ASTM E1578-18, Standard Guide for Laboratory Informatics. West
proof-of-concept systems need to be established before the appli- Conshohocken, PA, USA: ASTM International, 2018.
16. 全国认证认可标准化技术委员会(SAC/TC261); Laboratories - General
cation of any BSL-LIMS in large scale. Even though the system may requirements for biosafety (Chinese). GB 19489-2008, 2008.
be designed to fit in different niches, unexpected issues would 17. 中华人民共和国国务院; Regulation on the Bio-safety Management of Pathogenic
always be found in the trials.10 Because of the extra safety risks Microbe Labs (2016 Revision) (Chinese). In: Council Ss (ed). Order No. 666 of
the State Counci, 2016.
related to improper management of biosafety information, it is 18. Craig T, Holland R, D’Amore R, et al. Leaf LIMS: A Flexible Laboratory
always necessary to have a newly developed BSL-LIMS tested in Information Management System with a Synthetic Biology Focus. ACS Synth
small scale for enough time before dispensing it to more users. Biol. 2017;6(12):2273–2280. https://doi.org/10.1021/acssynbio.7b00212.
19. 中华人民共和国卫生部; Directory of Human Transmissible Pathogenic Microbes
Another aspect that should not be omitted is the data security
(Chinese). 2006.
in BSL-LIMS. Since the databases used by BSL-LIMS may be public, 20. (PHAC) PHAoC; Pathogen Safety Data Sheets.
internal, or confidential, the system must be able to distinguish the 21. National Academies of Sciences E, Medicine. Gene Drives on the Horizon:
different type of databases and prevent the leakage of protected Advancing Science, Navigating Uncertainty, and Aligning Research with Public
Values. Washington, DC: The National Academies Press, 2016.
data. From this point of view, it might be best to put the BSL- 22. Lunshof JE, Birnbaum A. Adaptive Risk Management of Gene Drive
LIMS in a local area network (LAN), isolating it from all possible Experiments:Biosafety, Biosecurity, and Ethics. Appl Biosaf. 2017;22
unauthorized access. If it is impossible, then an intermediate con- (3):97–103. https://doi.org/10.1177/1535676017721488.
23. Macher JM, Gold D, Cruz P, Kyle JL, Durrani TS, Shusterman DHandbook of
nection like the virtual private network should be set up to encrypt Occupational Safety and Health. Hoboken, NJ, USA: John Wiley & Sons, Inc.;
data transmission between internal and external databases, and 2019:147–197. https://doi.org/10.1002/9781119581482.ch6.
prevent data leakage. 24. Singh K. It’s time for a centralized registry of laboratory-acquired infections.
Nat Med. 2011;17(8):919. https://doi.org/10.1038/nm0811-919.
25. Weinstein RA, Singh K. Laboratory-Acquired Infections. Clin Infect Dis. 2009;49
Declaration of Competing Interest (1):142–147. https://doi.org/10.1086/599104.
26. Leveson N. A new accident model for engineering safer systems. Saf Sci.
2004;42(4):237–270. https://doi.org/10.1016/S0925-7535(03)00047-X.
The authors declare that they have no known competing finan- 27. Nezu Y, Hayashi R, Yamamoto H, et al. Visualization of activity in university
cial interests or personal relationships that could have appeared laboratory for experimental accidents/incidents prevention using non-
to influence the work reported in this paper. empirical approach. 環境と安全. 2019;10(2):45–47. https://doi.org/
10.11162/daikankyo.E18PROCP46.
28. Skinhøj P, Søeby M. Viral hepatitis in Danish health care personnel, 1974–78. J
References Clin Pathol. 1981;34(4):408–411. https://doi.org/10.1136/jcp.34.4.408.
29. Harding AL. Byers KB; Epidemiology of Laboratory-Associated
1. Gibbon GA. A brief history of LIMS. Lab Autom Inf Manage. 1996;32(1):1–5. Infections. Biological Safety: American Society of Microbiology; 2006.
https://doi.org/10.1016/1381-141X(95)00024-K. 30. Higgins JJ, Weaver P, Fitch JP, Johnson B, Pearl RM. Implementation of a
2. Goodman N, Rozen S, Stein LD; The LabFlow system for workflow management personnel reliability program as a facilitator of biosafety and biosecurity
in large scale biology research laboratories. Proceedings. International culture in BSL-3 and BSL-4 laboratories. Biosecurity and Bioterrorism : Biodefense
Conference on Intelligent Systems for Molecular Biology 1998;6:69-77. Strategy, Practice, and Science. 2013;11(2):130–137. https://doi.org/10.1089/
3. Ludäscher B, Altintas I, Berkley C, et al. Scientific workflow management and bsp.2013.0024.
the Kepler system. Concurrency and Computation: Practice and Experience. 31. Asfaw YG, Reynolds R, Alderman S, et al.; Managing Research Animal
2006;18(10):1039–1065. https://doi.org/10.1002/(ISSN)1532-063410.1002/ Specimens and Laboratory Safety. ILAR Journal 2018;59(2):144-149. doi:
cpe.v18:1010.1002/cpe.994. 10.1093/ilar/ily017.
4. Skobelev DO, Zaytseva TM, Kozlov AD, Perepelitsa VL, Makarova AS. Laboratory 32. 张楠. Northeast Agriculture University applologized for the Brucella infection
information management systems in the work of the analytic laboratory. Meas among students and teachers (Chinese). http://news.sciencenet.cn/
Tech. 2011;53(10):1182–1189. https://doi.org/10.1007/s11018-011-9638-7. sbhtmlnews/2011/9/248521.shtm?id=248521 (Date Accessed 2011 Accessed,
5. McDonald MJ, Rice DP, Desai MM. Sex speeds adaptation by altering the date last accessed)
dynamics of molecular evolution. Nature. 2016;531(7593):233–236. https:// 33. Song L, Gao J, Wu Z. Laboratory-acquired infections with Brucella bacteria in
doi.org/10.1038/nature17143. China. Biosafety and Health. 2020. https://doi.org/10.1016/j.bsheal.2020.07.010.
6. World Health Organization WHO. Laboratory Quality Management System: 34. Ngo KA, Jones SA, Church TM, et al. Unreliable Inactivation of Viruses by
handbook, 2011. Commonly Used Lysis Buffers. Appl Biosaf. 2017;22(2):56–59. https://doi.org/
7. Melo A, Faria-Campos A, DeLaat D, Keller R, Abreu V, Campos S. SIGLa: an 10.1177/1535676017703383.
adaptable LIMS for multiple laboratories. BMC Genomics. 2010;11(Suppl 5):S8. 35. Akbari OS, Bellen HJ, Bier E, et al. Safeguarding gene drive experiments in the
https://doi.org/10.1186/1471-2164-11-S5-S8. laboratory. Science. 2015;349(6251):927–929. https://doi.org/10.1126/science:
8. Amen AM, Barry KW, Boyle JM, et al. Blueprint for a pop-up SARS-CoV-2 testing aac7932.
lab. Nat Biotechnol. 2020;38(7):791–797. https://doi.org/10.1038/s41587-020- 36. DiCarlo JE, Chavez A, Dietz SL, Esvelt KM, Church GM. Safeguarding CRISPR-
0583-3. Cas9 gene drives in yeast. Nat Biotechnol. 2015;33(12):1250–1255. https://doi.
9. Stuart R, Stewart J, Herrick RHandbook of Occupational Safety and org/10.1038/nbt.3412.
Health. Hoboken, NJ, USA: John Wiley & Sons, Inc.; 2019:37–48. https://doi.
org/10.1002/9781119581482.ch2.
34