Mobile biosafety level (BSL) 2 laboratories deployment: Strengthening the diagnostic facilities in Pakistan with emerging public health challenges and the way forward


 Availability of mobile laboratories can facilitate rapid on-spot detection of pathogens, monitor its presence in certain populations and inform health authorities to take immediate remedial measures. Currently available biosafety and biosecurity guidelines and policies may not completely articulate the increased demand to manage mobile units in infectious disease outbreaks in remote parts of the country for rapid diagnosis, and also allows research and epidemiological study take place appropriately.
 The main objective of this study is to evaluate the current limitations and develop and implement biosafety and biosecurity guidelines as well as the protocols for operations, security, and response plan of mobile biosafety level 2 laboratories and their deployment.
 Keeping in view the sensitivity of it, a comprehensive plan was developed to address it in view of Global Health Security framework. Biosafety and biosecurity protocols were developed including Risk Assessment Tool (RAT) fitting the needs and strengthen the diagnostic and epidemiological capacity in the field covering remote parts of country to fill the gaps observed during the COVID-19 pandemic.
 Currently the biosafety and biosecurity best practices guidelines and biosecurity policy and regulations are directed mostly towards static laboratories. A biosafety and biosecurity manual developed to adopt and meet the requirements for MBSL 2. For acute health infectious threats including the COVID-19 outbreak and other epidemics, rapid diagnosis can curb and mitigate the problem before it gets out of its boundaries creating significant health risks for the public and economy. The deployment of mobile laboratories will certainly help in curbing these catastrophes.



Introduction
The deploying of mobile laboratories can significantly improve field research, environmental tracking, health surveillance, and diagnostic studies.All individuals involved in the running of Mobile BSL2 laboratories are primarily responsible for all crucial aspects of biosafety and biosecurity.This responsibility entails looking out for the safety of colleagues as well as including labora-tory workers in safety considerations while looking out for communities and the ecosystem.Infectious diseases, like the COVID-19 pandemic has caused extremely high infection rates in areas with limited diagnostic laboratory assistance was available.Utilizing transportable laboratories can improve the ability to identify, characterize, and report any new infectious disease epidemic and alert public health officials so they can take the necessary actions to contain and prevent potential pathogen transmission. 1Maintaining diagnostic facilities is difficult in many countries around the world, particularly in remote locations with few healthcare facilities.Due to the fact that these diagnostic laboratories are frequently located in bigger cities and are connected to hospitals and medical facilities.In order to diagnose COVID-19 and other infectious illnesses, specimens must be collected and moved as soon as possible at ambient temperature to the laboratories for processing according to predetermined timelines.The goal was to ensure the highest level of protection and monitoring against physical, biological, and environmental hazards while facilitating the deployment of mobile BSL 2 laboratories in the local environment and keeping them up to date with recommended standards for biosafety and biosecurity protocols and guidelines. 2 A biosafety manual was developed in this scenario to tackle the challenges of deploying rapid response mobile BSL 2 laboratories across the whole of Pakistan.Its main goals were to create a secure working environment for mobile laboratory workers and related staff, safeguard mobile laboratory employees from potential biological hazards, increase the staff's proficiency in biosafety and biosecurity, and reduce physical and security risks associated with operating these mobile laboratories.In many areas of the globe, it has been noted that these mobile laboratories are frequently used in disease outbreak investigations requiring the handling, storing, and field studies of contagious agents.This propensity has sparked widespread worries about the biosafety and biosecurity of these mobile facilities as well as the adverse impact on public health and environment.It is also noted that there are no unified, single operational guidelines for biosafety & biosecurity being in place for these mobile laboratories.These fast mobile laboratories will provide and enhance the public sector capacity in Pakistan to rapidly deploy a sophisticated well equipped mobile laboratory infra structure.It will provide strategic response to hard-to-reach zones during an outbreak which can result in an epidemic or pandemic.The assigned laboratory workers would use this manual as a reference to make sure that biosafe laboratory activities were carried out in accordance with international best practices. 3A Biorisk Management System (BMS) is a methodical approach for dealing with biosafety and biosecurity issues in laboratories, also known as biorisk.In order to effectively manage infectious organisms, a clearly documented BMS must be established and put into place. 17,18A written standard operating procedure (SOP) created in the local expression details the steps for the task to be done.A risk assessment format should be used to evaluate the risks indicated at each phase, and appropriate mitigation actions must be taken.The primary concern in an MBSL 2 is unintentional exposure to an infectious pathogen that can infect laboratory personnel and members of the public.Aspects of biosecurity that must also be addressed include preventing theft, loss of biological material, and illegal access.A Biorisk Management System (BMS) must include incident reporting and follow-up in addition to hazard detection, risk assessment, and mitigation. 19In this context a prototype risk assessment tool (RAT) was developed to fulfil the needs of the mobile laboratories.All staff members should be informed of the BMS after it has been implemented and approved, and a printed copy should be made available for convenient reference. 5isks that the Mobile BSL2 Laboratories might experience during their operations include biological and physical security breaches making them extremely vulnerable as a result of such hazards and threats.In response, risk assessments will be conducted on a regular basis to make sure the laboratory has incident mitigation procedures in place.A group of procedures, methods, and techniques together referred to as incident management allow teams to identify, look into, and respond to incidents.It is a crucial component for businesses of every type and is necessary to achieve the majority of data compliance standards.The chain of command in incident management is based on job function rather than title.The incident management committee is responsible for managing each of the five steps of incident resolution which include 1. Incident Identification, 2. Logging and Categorization, 3. Incident Noti-fication and Escalation, 4. Investigation and Diagnosis, 5. Resolution and Recovery and finally Incident Closure.

Materials & Methods
With the support of foreign funding organizations (USAID), four Mobile BSL 2 laboratories were purchased in Pakistan to improve the country's field diagnostic capabilities in response to pandemic or epidemic alert.These MBSL 2 units were stationed in all four provinces of Pakistan in order to respond quickly in the event of an outbreak or in areas with dearth of facilities for the immediate detection of infectious illnesses.The cutting-edge technology displayed in Table 1 is just one of the key characteristics of these Mobile BSL 2 laboratories.
Class II Type A2 BSC, Fridge Freezer combo, DNA Extractor, Gen-eXpert, Realtime PCR Machine 4 Channels, PCR unit with UV light and HEPA filter, Floor standing Autoclave, Refrigerated High-Speed Micro Centrifuge, Advanced Multi-Purpose Clinical Centrifuge with Timer, Vortex Mixer, ELISA Plate Reader 96 Well, Elisa Microplate washer, Horizontal Electrophoresis, DNA/RNA Quantification System, Spectrophotometer, Hands-Free Disinfection Station (Fig. 1).(SeeFig.2.) Keeping in view the sensitivity of operations of these mobile laboratories the following security measure were adopted to make it safe and secure in the travelling and when they are stationed.All authorized personnel of mobile BSL2 laboratory will have access only through biometrics, CCTV in each room and two external cameras, two-zone fire alarm system tied into control system.Intercom system (three-station system, one installed in each room as well as one at the main entrance door), Multi-zone burglar alarm system, including motion sensors for each room, keypad for arming and disarming, siren, emergency panic button, BSL-2 sensors installed in enclosures that can withstand the chemicals associated with room decontamination, Burglar bars on windows, Access control system with keycard access (upon arrival to the destination city/ province), all internal doors fitted with red (open door) and green lights to ensure proper door closure and airflow, Satellite tracking system on each laboratory, trailer/power bank that are active 24/7/365, professionally trained security guards and drivers, SOPs easily accessible in each laboratory.
In order to sustain the performance and competence of these mobile laboratories, they will be inspected by the manufactures engineering team three times in the first year and twice in the next two years for preventative maintenance.It will be made mandatory for the Mobile BSL 2 facility for annual service and equipment re-certification, refresher training for user with local biosafety experts, annual certification of BSCs and performance verification.Hands-Free Disinfection Station

Results
With the assistance of biosafety consultants with international certifications in biorisk management as well as other technical and security specialists for operations of the equipment and its performance validation, the biorisk handbook was created with an eye on the needs of moving laboratories.Since the well-trained crew in biosafety and other processes indicated as per the demand of the field will be vital to the safe and effective operation of the Mobile BSL 2 laboratories.This manual which is developed, documents all essential aspects of biosafety and biosecurity for mobile labs to ensure maximum protection and monitoring against physical, biological, and environmental hazards available on this link https:// lmis.gov.pk/bsl2/manuals/FinalMobileBSL-2manual.pdf.The SOPs provide standardized guidelines for a safe working environment for healthcare workers.Safe and secure movement and deployment of the mobile labs in the field are other mainstays of this manual.The respective provincial health departments have nominated staff for smooth lab operations according to the guidance provided in the lab manual.The nominated staff have been trained on the different modules of the biosafety lab manual.The biosafety handbook additionally included annexures that addressed every significant and sensitive aspect necessary for activities both within and outside the MBSLs.It is composed of Security Management Plan, Incident Management Plan, Incident Reporting Form, Serious Incident Reporting template, Event Management, Layout plan of the mobile BSL-2 laboratory, SOPs for avoiding Occupational Hazards Occupational Health Support Service Elements, Rapid Inactivation Protocols, Facility Security Plan, Risk Assessment Tool (RAT), Field Certification Protocols for Biosafety Cabinets NSF/ ANSI/49 Standard, SOPS for Autoclave, Fire Evacuation SOPs, SOPs for Laundry, Rapid Inactivation Protocols. 3A check list is also included for biosafety and biosecurity requirements.Tables 2, 3. Fig. 3).

Discussion
8][9] However, the existing guidelines regarding biosafety and biosecurity for the MBSLs remain inconsistent among the countries and no single policy and guidance is available on biosafety and biosecurity requirements.As future offers certain advantages in controlling biological threats with the help of these MBSLs equipped with latest diagnostic equipments, novel strategies and technical expertise yet there are risks involved in these deployments which have to be clearly understood and communicated to the countries operating MBSLs.In some previous report and studies, it was clearly mentioned and understood that there is no specific policy and programmatic initiatives were in place regarding MBSLs and their related operational risks. 10This study also prioritized the biosecurity related hazards and risks involved with MBSLs which were evaluated and provided guidance on security measures to protect the workers, local population, and surrounding environment.
In geographical locations where diagnostic laboratory support is limited, infectious disease outbreaks such as the current COVID-19 pandemic can result in exceptionally high infection rates.The use of mobile laboratories can enhance the potential to detect, diagnose, and report any emerging infectious disease outbreak and inform public health authorities so that they can respond appropriately to limit and prevent potential pathogen transmission. 15,16Several resources were used to create this manual, National Health Vision Pakistan 2016-25, provincial health strategies, National Biosafety and Biosecurity Policy 12 and the World Health Organization (WHO) Laboratory biosafety manual 4th edition. 11To strengthen Pakistan's capacity to detect public health events due to infectious diseases, including COVID-19, USAID has contributed to the procurement of four Mobile Biosafety Level 2 Laboratories (BSL2) for federal and provincial governments and regions.These include one mobile laboratory for Islamabad Capital Territory (ICT) [to cover ICT, Azad State of Jammu & Kashmir (AJK) and Gilgit Baltistan (GB)], Khyber Pakhtunkhwa (KP), Punjab, and Sindh (to cover Balochistan), respectively.These laboratories will be instrumental in diagnosing public health events, especially in remote and hard-to-reach, areas as well as during outbreaks, covering epidemics, pandemics, and natural disasters.
However, these MBSLs operation should be able to ensure that clinical and environmental samples are safe and secure, a deficiency on this could potentially incense an epidemic outbreak.Also, contingency measures in MBSLs must undertake full assessment of the present health infrastructure, available resources and complete knowledge and awareness of the risk among the target population as part of deployment and plans for operations.Keeping in view the personal safety and security challenges for the positioned employees it is important that they are well educated and trained in biosafety and biosecurity.Hence it is recommended that future contingency operations in response to pandemics and epidemics in remote and difficult to work areas should include biosecurity related training to ensure the steadfastness of the MBSLs and their supporting systems. 4It is important that policy makers have to take a detailed opportunity cost analysis covering overall review and applicability of present biosafety and biosecurity policy and guidelines to the exclusive MBSLs infrastructure and operational process.It must be ensured that all the regulatory framework is studied prior to abide by norms of biorisk management especially for MBSLs and any modifications to guidelines for MBSLs must be able to retain the best biosafety practices observed at BSL 2 laboratories all over the globe. 13,14,6.

Conclusion
As these laboratories have certain safety and security problems while handling pathogenic organisms in a constrained environment may be responsible for unintentional occupational exposure and risks to the workers, community and environment.It can also be a source of nefarious use through intentional loss, theft, misuse by the rogue elements.In this study the biosafety manual was developed to basically meet the requirements for rapid response MBSLs.These Biosafety and Biosecurity guidelines, are aimed to fill the gap in current guidelines, policy and regulations for Mobile BSL 2 laboratories.A risk assessment prototype model was introduced to address the need of these MBSL 2 laboratories.Additionally targeted policies, guidelines and regulations are important for these new and moving vehicles with options to enhance the Biosafe and Biosecure working in these sophisticated MBSLs.It is recommended to follow up with the process of developing some unified biosafety & biosecurity guidelines for these rapid response laboratories involving all the international stakeholders in its development.

Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Fig. 1 .
Fig. 1.Layout plan of the mobile BSL-2 laboratory (Figure Replaced).In addition, a model Risk Assessment Tool (RAT) was developed to address the risk assessment portfolio which is backbone of biosafety and biosecurity.Figure NO. 2.

Table 2
Check List for the biosafety of MBSL 2.