COVID-19 and Beyond: Safety and Design Considerations for the Development of a Mobile Biocontainment Laboratory

Abstract

Introduction:

An infectious disease outbreak like the current COVID-19 pandemic can lead to particularly high infection rates in areas where diagnostic laboratory support is limited. The deployment of mobile laboratories can help to detect pathogens, monitor the presence in a population, and inform public health authorities to take measures aimed at reducing pathogen spread.

Materials and Methods:

Available layouts and operational descriptions of mobile laboratories were analyzed for their suitability for the envisioned purpose and to assure high standards of biosafety and biosecurity. Recent media coverage on creative solutions for the diagnostics of SARS-CoV-2 (drive-through test centers, self-swab, inverse gloveboxes to protect health care workers) from various countries were considered.

Results:

A minimalistic and optimized design to construct a multifunctional laboratory on the chassis of a regular-sized box truck is proposed and can serve as a blueprint to rapidly develop additional diagnostic capacities.

Discussion:

For acute health threats including the current COVID-19 outbreak, rapid diagnosis of infection is key to recommend measures aimed at preventing the spread of the pathogen. Laboratory layouts that are similar to the one proposed here are used in stationary setups, and mobile laboratories have been built on varying platforms (trailers, shipping containers, etc).

Introduction

The world is currently battling a pandemic that is caused by a novel coronavirus termed SARS-CoV-2. ¹ Timely and accurate diagnostics of the etiological agent and the subsequent isolation of infected individuals are key measures to contain the spread of the virus. ^{2 -4} Many regions of the world are facing the challenge of quickly ramping up diagnostic capacities, especially in remote areas, where people do not readily have access to health care facilities. Diagnostic centers are typically only found in major cities and are often associated with larger hospitals. The diagnosis of COVID-19 requires the collection of a respiratory specimen (eg, throat swab sample), nucleic acid extraction, and real-time reverse transcriptase polymerase chain reaction and is able to provide results in about 4 hours. ^5,6 Several descriptions of mobile laboratories and reports on the experiences to operate these in the field were published previously. ^{7 -11} Here, we provide design suggestions for a mobile biocontainment laboratory based on widely available standard-sized trucks that can function as a diagnostic facility during outbreaks or support research activities when diagnostic capacity is sufficient. Our proposed setup allows for almost unrestricted mobility of the laboratory even in difficult terrain and makes time- and resource-consuming sample transport obsolete. Furthermore, preferred laboratory procedures are described that need to be modified, validated, and approved based on the local requirements and risk assessments.

Constructional Considerations

Common box trucks range in length from 16’ (4.8 m) to 24’ (7.3 m), and this compressed footprint necessitates the best possible use of the available space (Figure 1). The driver’s cabin, which is separate from the laboratory, is a clean area. The work space must at least consist of 2 rooms, an anteroom with storage capacity that doubles as a change room before entering the laboratory area and the actual laboratory. Laboratory surface finishes should be smooth, easy to clean, impermeable to liquids, and resistant to the chemicals and disinfectants normally used in the laboratory; the floors should be slip-resistant. Mobile biocontainment laboratories (MBL) must also be designed and constructed to be exceptionally durable. To achieve this, careful consideration to the choice of materials and construction details must be given. The interior walls of the MBL should be as seamless as possible. Required joints should be sealed with flexible sealants and checked frequently. Smooth fiber-reinforced plastic plates are a good choice for the inside walls and ceiling. For the floor, a single-piece vinyl or rubber covering is ideal because they are durable and chemical resistant and can withstand an intense cleaning regiment. If this type of flooring is unavailable, care should be taken when sealing the floor to make it impervious to liquids and durable for the intended use. High-quality epoxy floorings can be used for this purpose. Seamless stainless steel casework is the gold standard but can often be unavailable. Vinyl flooring can be used to cover and seal table surfaces, but any wood-based or other porous materials must be avoided. The edges of laboratory benches and cabinets should be rounded or otherwise protected to prevent injury and snagging of personal protective equipment (PPE).

Figure 1.

Schematic representation of a closed truck body modified to accommodate a minimalistic diagnostic laboratory. 1. Anteroom (separate gowning room with storage). 2. Fridge/freezer combination. 3. Reverse transcription (RT) polymerase chain reaction (PCR) machine. 4. Class III biological safety cabinet (BSC) glovebox (can be replaced with a Class II BSC). 5. Polymerase chain reaction workstation. 6. Air conditioning. 7. Driver’s cabin.

In the anteroom, a line of demarcation of the floor separates clean and dirty areas and will be crossed during the donning and doffing of PPE during entry and exit of the laboratory. Furthermore, the anteroom has to provide a facility to deposit and disinfect the outside bag of received specimens and room for storage of PPE and reagents. A fire extinguisher and first aid box will be present in the anteroom and in the laboratory area, complemented with a spill kit in the laboratory. Desirable but optional is the installation of a CCTV and alarm system. A fire escape needs to be present in the main laboratory in case the exit via the anteroom is blocked. This can be achieved by the installation of a small additional airtight door or a multilayered glass window, which are permanently sealed from the outside but allow the removal of a rubber lip from the inside in the case of emergency. A divider wall with a sealed door between anteroom and the laboratory area is required to prevent outside air from entering the laboratory. The laboratory area should be equipped with a Class III biological safety cabinet (BSC), commonly referred to as a glovebox, for additional safety during handling of diagnostic samples. Although less suitable for mobile applications, a Class II BSC is acceptable in the case that a Class III BSC cannot be used. The airflow in the Class II might be disturbed after movement of the MBL, and a hand-held anemometer (air flow meter) should be used for validation purposes. The integrity of all air filters is an additional concern that requires constant monitoring. Ideally, a handwashing/disinfection station is available near the exit of the laboratory, but it can be replaced with a setup just outside the truck in the open area or a washroom in the direct vicinity. In this case, a double glove policy needs to be in place inside the laboratory whereby the outer glove is removed before entering the anteroom during the exit procedure. A heating, ventilation, and air conditioning (HVAC) system must be activated during the operation of the MBL to ensure a comfortable temperature for the laboratory workers that also allows for the safe operation of the equipment. No negative pressure in the MBL in relation to ambient air pressure is required, but regular overpressure decay tests using a dedicated pressure inlet are advisable. In case of an observed pressure drop exceeding the acceptable range, small cracks in the MBL outer walls, which might originate from the movement of the setup, need to be detected and permanently sealed.

Additionally, a laboratory bench with a polymerase chain reaction (PCR) hood and a reverse transcription (RT) PCR machine with a computer and a refrigerator/freezer combination is required. All fragile equipment needs to be stored in hardcase boxes, and all biohazard waste needs to be cleared before movement of the MBL. A mobile autoclave is ideal, but the safe transfer of solid biohazardous materials to an offsite autoclave facility or incineration onsite if allowed by local legislation can be considered. The MBL needs a power supply in the form of a power generator or a cable connection to the electrical grid. It is advisable to work out detailed checklists specifying the start-up and shut-down procedures of the MBL. A suggested checklist summarizing major operational items to safely setup and operate an MBL should be amended to represent the individual workflow and local requirements (Figure 2).

Figure 2.

Checklist for the safe operation of a mobile biocontainment laboratory. This list can only serve as a guideline and should be modified and extended based on individual circumstances.

Procedural Considerations

The safe and efficient operation of the MBL will crucially depend on well-trained staff. A medical doctor or nurse is required to take anamnesis (patient history to enquire about current complaints and potential exposure) and to perform sample collection. Two laboratory personnel that are trained in the safe handling of specimens, nucleic acid extraction, and qPCR operation are needed to run the laboratory. Finally, medical personnel have to make a diagnosis either at the laboratory or offsite.

Swab samples are obtained outside the MBL while wearing appropriate PPE. Samples are labeled, stored in sealed bags, and transferred into the laboratory. Personnel don appropriate PPE (including gloves, gown, and N95 mask) in the anteroom and disinfect sample bags individually before entering the lab area. Alternatively, samples are transferred into the laboratory via a pass-through box equipped with an interlocking mechanism and a decontamination step during sample import. Samples are transferred and opened inside the glovebox or BSC, and nucleic acid is extracted using a validated method. A tabletop centrifuge is available in the glovebox/BSC. PCR reagents are prepared inside the PCR work hood and aliquoted. Nucleic acid is added at the bench; the plate or tubes are sealed and subsequently transferred out of the glovebox or BSC to the PCR machine. PCR results are exported and analyzed at the computer. The inside of the glovebox or BSC is decontaminated carefully while observing appropriate contact times before the next batch of samples is imported. Liquid biohazardous waste should be collected in appropriate airtight containers, sealed, and allowed to remain inside the lab for the required exposure time for disinfection. Liquid waste containers are then surface-decontaminated and their contents emptied into the sewage system. A suitable disinfectant should be chosen based on the pathogens reasonably expected to be present in the specimens, the safety of handling the disinfectant, and potential incompatibilities of the disinfectant with other chemicals used in the MBL. In case solid medical waste is generated, it should be collected in sturdy leakproof containers, labeled according to local regulations, and secured in an additional stainless steel container to allow safe transport back to a larger laboratory or hospital that has arrangements for appropriate disposal of medical waste. To minimize the risk of contamination, no derivatives of viral genomes are allowed inside the diagnostic laboratory (plasmid DNA, PCR amplicons). If viral RNA is detected in the diagnostic assay, a product degrading RNAses and DNA is preferred to clean surfaces where extracted RNA is handled.

Biorisk Management Systems

A biorisk management system (BMS) is a systematic approach to manage biosafety and biosecurity (combined also referred to as biorisk) issues in a laboratory. ¹² When dealing with infectious agents, it is very important to establish and implement a simple written BMS. The procedures for the work to be performed are described in a written standard operating procedure (SOP) prepared in the local language. Hazards identified at each step should be assessed in a matrix risk assessment, and mitigating measures have to be implemented (Figure 3). The predominant hazard in an MBL is the unintended exposure to an infectious agent that can result in disease contraction of laboratory personnel and the community. Additionally, various biosecurity aspects have to be addressed, including the prevention of unauthorized access, the loss of biological material, and so on. In addition to hazard identification, risk assessment, and mitigation, incident reporting and follow-up is an essential part of a BMS. Once a BMS is in place and approved, it should be communicated to all staff involved, and a printed version should be available for easy reference.

Figure 3.

Suggested risk assessment based on a matrix scheme assessing the likelihood and severity of an event. Risk levels are indicated by color. Red denotes high risk, orange medium risk, and green low risk. Risks should be reduced by applying mitigating measures to medium or low before the intended work can start.

Conclusion

The proposed design of the biocontainment laboratory design is not a one-fits-all solution and must be altered to suit local needs. The MBL can accommodate additional laboratory equipment, such as microscopes, plate readers, blood gas analyzers, and so on, required to perform different types of diagnostic assays. The implementation of an MBL requires careful assessment of the particular national health care systems and can only complement existing infrastructure. The MBL is not intended to replace primary care clinics or hospital laboratories but might extend the capacities for rapid and accurate diagnostics, especially in rural areas. Sufficient funding needs to be secured to cover the setup of the MBL as well as its long-term operation, consumables, manpower, and maintenance costs. When time is of the essence, biosafety and biosecurity remain essential considerations during the implementation of novel diagnostic concepts to combat acute pubic health threats.