Wuhan BSL-4: Engineering Review

WARNING

This presentation is about the WIV P4 lab and its advanced engineering, with some context.
Please do not interpret this as suggesting that a lab leak scenario may have involved the P4.
As we know, all BatCoV work in Wuhan was done in P2 and P3 labs, across multiple sites (WIV Zhengdian and Xiaohongshan, Wuhan Uni, CDC labs, etc). Authorisation to use the P4 for coronavirus research was not actually granted until after the outbreak — until then it was purely a P2 / P3 pathogen. See this presentation for the Wuhan labs of interest.

1. Introduction — The challenges of high containment engineering

3D view of Wuhan BSL-4

1.1 Submarines

In Das Boot, the 1981 movie, U-96 lands on the sea shelf at the depth of 280 meters after an uncontrolled dive. Haunting cracking sounds resound and leaks spring up. The captain shouts the memorable “Wasser muss ‘raus” and the crew works desperately to regain control of the submersible while they start running out of oxygene.

1.2 Nuclear reactors

Maybe a better analogy would thus be with radioactivity containment.

A Farmer’s graph, source: Idaho National Laboratory (a U.S. DOE National Laboratory)

1.3 High biocontainment laboratories

Developed nations such as the US, France, UK and Japan have a long history of running a fleet of nuclear power stations, unfortunately punctuated by the occasional accident (TMI, Fukushima). They have generally learned the hard way that any lapse in design, construction or operation or effective regulation of nuclear reactors may have an extraordinarily high price. That lesson-learnt may generalize to high biocontainment labs to a certain degree.

Simplified adequacy of ‘nuclear infrastructure’ in selected regions of the world. From best (dark blue), to OK (pale blue), worrisome (yellow) and lacking (red). Source: W. Martin and B. Richter, International Issues Related to Nuclear Energy (Stanford, 2012).

2. Background: Needs and Ambitions

2.2 Chinese Needs

The 2002–03 SARS outbreak convinced the Chinese government that the country needed to have it own BSL-4 laboratories in which it could drive local research on dangerous pathogens . In January 2004 the French and Chinese governments signed a “Memorandum of Understanding (MOU) on the Prevention and Combat of New Infectious Diseases”. That memorandum encompassed cooperation between the two countries on 4 pillars:

  • scientific research cooperation,
  • personnel training,
  • legal and regulatory standards
  • laboratory construction

2.2 Chinese Ambitions

An essential background to the 4 pillars of the MOU signed by the two countries is that the envisaged cooperation with France on the Wuhan BSL-4 should pave the way for for China to achieve as soon a reasonably possible a full strategic autonomy in construction of BSL-4 labs, by carefully learning from foreign examples while developing local alternatives to foreign engineering and equipments.

  • the structural engineering of the P4 (building shell and stainless steel rooms) largely used homegrown capacity and technology,
  • even if previously 80% localization of equipments had been reached in a model laboratory, most of the P4 key equipments were actually imported, sometimes to be modified (such as the Siemens control system), as China was not yet ready to fully trust its homegrown technology in that domain.

2.3 French Ambitions

The picture would neither be complete nor fair if we did not mention the French government’s motivations for the Wuhan BSL-4 project.

3. Complex Engineering

3.1 Alterations to the French blueprints

The design of the BSL-4 was based on French BSL-4 in Lyon, the largest BSL-4 in Europe at the time (and to this day) that had opened in 1999. The French design underwent several Chinese modifications or improvements.
The introduction of modifications happened throughout the design, construction and operation phases.

Main differences between the Lyon BSL-4 reference and the Wuhan BSL-4
  • a laser welded stainless steel shell resting on seismic dampers (to avoid cracks)
  • new software (at higher sampling rate) for the imported Siemens control system.
  • improvement of HVAC and of life support system.
  • new biosafety standards
Wuhan BSL-4 Differential Air Pressure and Flow Diagram, modified with the patent information. Source: patent CN209960702U Exhaust system for biological safety laboratory

3.2 The question of FOAK

These departures from the French reference design (which in 2008 was proven technology that had been operating for 9 years) raise some questions, especially as these design changes made it a double first-of-a-kind (‘FOAK’):

  • FOAK for the technology after these extensive changes to the blueprints, especially for the stainless steel containment
  • FOAK for China, as being officially its very first P4 to enter into service
From https://www.sciencedirect.com/science/article/pii/S2588933818300128

4. Project Pains

4.1 A clash of objectives and cultures

The BSL-4 project had to navigate its way between the initial French design with its expectations of clear and careful project management, and the reality of designs absorbed and reworked on the go by the Chinese side and eventually built by Chinese companies with limited relevant experience.

  • The French engineering side expected minimal changes to the blueprints, little improvisation, careful construction involving some French companies (or at least Chinese companies that the French side would be comfortable with), one of them acting as ‘maître d’œuvre’ [10], all following the French proven project management approach.
  • The Chinese side wanted to absorb and tweak the technology along the way (possibly using the experience acquired in their their model labs) with an aim of technology independence, while going through the construction and the required re-engineering in a much more ad-hoc and improvised way, with its chosen companies [11] and without a maître d’œuvre.

4.2 Unhappily married

One may appreciate the references to all these difficulties mentioned above, plus a certain nationalist angle, in the following Chinese summary of the project:

5. Location and Overview

5.1 Site

The location for this ‘first’ BSL-4 in China was Wuhan. This was not because Hubei province is particularly susceptible to animal or human epidemics. Arguably it is rather average, by contrast with Yunnan with its Kunming BSL-4, and Guangdong where the Chinese CDC may soon have a second P4. The location was instead chosen due to the following reasons:

  • The BSL-4 was to be built under a Sino-French cooperation and Wuhan is the most French of all Chinese cities, with many French companies present there with production facilities.
  • The Wuhan Institute of Virology (WIV) of the Chinese Academy of Science, with its main buildings in the centre of Wuhan, was a perfect partner for the Chinese side of the Sino-French project. .
  • Wuhan has many top level universities and was designated as a ‘silicon valley’ of bio-technologies in the national plans.

5.2 Layout

WIV — Wuhan National Biosafety laboratory, and comprehensive research center, Zhengdian Gold Industrial Park, general plot plan for environment permit
  • The BSL-2 & 3 units, the animal room buildings, with boiler and utilities (south east of the map above), were built between 2006 and 2012. The animal room received its experimental animal use permit in 2012. The BSL-3 suite of labs was accredited by the China National Accreditation Service for Conformity Assessment (CNAS) in 2018 and approved by National Health and Family Planning Commission (NHC/NHFPC)in November 2019 (after the BSL-4).
  • The BSL-4 suite of labs, constructed between 2011 and 2016, accredited by CNAS and approved by NHC in 2017, entered into operation in 2018.
Wuhan BSL-4 site work in 2012 (HSE note: people should have had safety shoes and proper site works PPE)
  • The comprehensive research center, west of the campus, and an extension of the animal building (east side, on the right of the map) were built between 2017 and 2021, with temporary construction facilities just beside the BSL-3 and BSL-4, downstream from the wind.
‌The construction of the research center (red buildings on the right) near the Wuhan BSL-4 (middle) of Wuhan Institute of Virology, Chinese Academy of Sciences, in 2017

6. Engineering phases

The engineering design of the BSL-4 was done in four main steps:

a. French blueprints (Dec 2008)

A first set of drawings and specifications was issued by the French companies Tourret Jonery Architectes, Altergis and ClimaPlus in December 2008. [Validate link]

b. Chinese modifications to the blueprints (2009–10)

Reviews and comments were then incorporated in some revised drawings and specifications from the Chinese Design Institute:

  • Revised standard “General Requirements for Laboratory Biosafety” (GB19489–2008)
  • Change in layout, HVAC system, and waste disposal system
  • Change in building structure and seismic resistance, wall isolation and sealing, airflow/gas/liquid and some key technologies for laboratory design and construction such as solid-phase harmful biological factor treatment, life support system
  • Laboratory enclosure structure in stainless steel
  • Light steel keel structure

c. Further changes to specifications (2011-15)

More Chinese innovations were introduced over the construction and fitting years:

  • Fire-fighting system
  • Industrial control system

d. Adjustments from trials and operation (2016–20)

Further alterations and improvement (some patented) were introduced before certification, largely based on trials:

  • UPS battery room extension
  • Airlock, air exhaust ventilation
  • Pneumatic doors improvement
  • Contaminated water treatment
  • Autoclave and air incinerator
  • Cleaning solutions
WIV bids in second 2nd semester 2019 — ref WIV procurement table Appendix 1

7. Codes and Standards

7.1 Certification

Unsurprisingly, the French side was not that keen to take the risk of certification after all the peregrinations of the design and of the construction. For all practical purposes, the French enthusiasm and involvement in the project peaked in its early years. From the end of the construction phase (2015) the French involvement into the project was reduced to a minimalistic representation [9].

English Compilation of Chinese Biosafety Laws, Regulations and Standards (Left) Selection of French Biosafety Laws and Regulations” (right)

7.2 Next stages

Following domestic certification, the WIV was approved in 2018 by the National Health and Family Planning Commission (NHFPC) to work on Nipah virus, Ebola and Crimean-Congo hemorrhagic fever, making it officially operational.

8. Lay-out of the BSL-4 lab suites

8.1 Plans

In the circulation plan of the Wuhan BSL-4 below, the white lines showing where people circulate and the red lines are for materials and animals flows. The blue shaded floor is where the labs are located, while the yellow shaded floor shows the animal rooms and dissecting room (in the middle).

Wuhan, BSL-4 Laboratory floor layout and circulation. The pillars of the biosafety level four : national biosafety laboratory, Wuhan (P4). Zhejiang Education Press, Hangzhou
Wuhan BSL-4 core lab layout — WIV

8.2 Evaluation

As a result of that design, the north east shower room has three doors instead of two, with one door to the animal lab and one door to the small cell culture lab (lab 3), the 3rd door being to the standard PPPS room. This is quite a complex situation.

Wuhan BSL-4 shower room shared with lab 3 and animal room 2, has a three-door airlock system
Weak point, with three doors at the junction. Disinfection room N2 with 5 large doors. Disinfection room N2 has 5 doors for 4 walls.

9. Stainless steel containment

9.1 Innovation

One important innovation that differed from the Lyon referenced BSL-4 is that the wall and ceiling of the laboratories are stainless steel, laser welded to ensure airtightness.

9.2 Potential corrosion issues

One complication with stainless steel is that the change from urethane panels to stainless steel implies different operational procedures to avoid stainless steel corrosion.

FOI’d emails
Extract for WIV BSL-4 environmental report , annex 20, dated 2018. ref appendix 2
English translation of Extract for WIV BSL-4 environmental report , annex 20, dated 2018.
Extract for WIV BSL-4 environmental report , annex 20, dated 2018. ref appendix 2
English Translation of the Extract for WIV BSL-4 environmental report , annex 20, dated 2018. ref appendix 2

9.3 Other possible issues with stainless steel containment

The Chinese model of stainless steel sandwich panels and structure may cause bended wall which may lead to loose connections, as can be seen in these photographs.

Wuhan BSL-4 Laboratory room 2018, Loose connection of the cable tray above the door
Wuhan BSL-4 Lab room 2015, marks and bended wall

10. Equipment Procurements

Single source procurement of equipment and spares for WIV BSL-4 includes the following equipment (refer to appendix 1, WIV sourcing table) [check link]:

  • HEPA H15 from Camfil Group, Sweden
  • Chemical shower system from PLASTEUROP, France
  • Airtight door from PLASTEUROP, France
  • Life support system from Belair
  • Live toxic wastewater treatment station with spare parts (ACTINI2835 Type)
  • Double door autoclave (GEB 6613–2, GEB 6915–2)
Table of supply of main equipment for Wuhan BSL-4 lab

11. Key Equipment Alterations

In this section, we shall review some of the design and equipment alterations using open source information.

Extract: ‘Biosafety Laboratories in Wuhan, China’

11.1 Control System

Importance

The control system in a maximum containment laboratory is of utmost importance. For instance it monitors the stability of the negative pressures inside the laboratories and other rooms (chemical shower room which also operates as an airlock, changing room etc).

Close view on Lab 2 of Wuhan BSL-4, with indication that an experiment is ongoing (biosafety triangle, and written in red below: “experiment on going”).
Wuhan BSL-4 control system, monitoring screen with differential pressure. we recognize lab 1 on the screen. Source: The construction and research team of Wuhan P4 laboratory of Wuhan Institute of Virology, Chinese Academy of Sciences

Modifications

The WIV also modified the control system after reception from Siemens. One modification was to remove the backend access feature, which can easily be understood under cyber security grounds. In that same article, Zheng & Li explain:

Evaluation

While they are certainly good reasons for these changes beyond backend access, it is a bit difficult to understand why the WIV would try to improve a system that they had never used and on which WIV had no operational feedback.

High-reliability automatic control cabinet of Wuhan BSL-4 laboratory- The pillars of the biosafety level four : national biosafety laboratory, Wuhan (P4). Zhejiang Education Press, Hangzhou
Dual mains loop power supply system of the Wuhan BSL-4 laboratory; The pillars of the biosafety level four : national biosafety laboratory, Wuhan (P4). Zhejiang Education Press, Hangzhou
The host computer server of Wuhan BSL-4 laboratory automatic control system; The pillars of the biosafety level four : national biosafety laboratory, Wuhan (P4). Zhejiang Education Press, Hangzhou

11.2 Firefighting system

Choice of extinguished agent

Fire is a real hazard in a laboratory, to be taken at utmost importance. Yearly fire fighting drills were done at WIV, and the National Health Commission (NHC) did a special inspection of fire safety of the Wuhan National Biosafety Laboratory in January 2019.

Extract Laboratory biosafety manual. (3rd edition)

Evaluation

Heptafluoropropane, also called FM200, is a compressed gaseous fire suppression agent; it is commonly used in places where water is to be avoided, such as computer rooms, electrical rooms.
As a compressed gas in a liquid form within the extinguisher cylinder, its decompression may cause a peak of positive pressure, as mentioned in the article. Moreover, at high temperature FM200 decomposes in hydrogen fluoride, which is a highly toxic gas that needs ventilation. It is also corrosive.

  1. find a way to evacuate the gas produced without evacuating dangerous pathogens,
  2. make sure that the peak of positive pressure generated by the depressurisation of the extinguisher gas does not interfere with the negative pressure gradient,
  3. make sure that the corrosive gas does not damage its the stainless steel structure.

11.3 UPS and battery room

Standard setup

There are three power sources for the lab: the city grid electricity network, a dual UPS (Uninterrupted Power Supply) and the dual diesel generator electricity supply. The UPS and the diesel generator offer of a guaranteed power supply so that in the event of loss of grid power, biological safety maybe guaranteed without loss of power.

UPS Uninterruptible power supply system of Wuhan P4 laboratory; The pillars of the biosafety level four : national biosafety laboratory, Wuhan (P4). Zhejiang Education Press, Hangzhou
The standby dual diesel power generation system of Wuhan P4 laboratory; The pillars of the bio-safety level four : national biosafety laboratory, Wuhan (P4). Zhejiang Education Press, Hangzhou

Dealing with grid power instability

Power instability in the grid can affect the negative pressure gradient, the life support system (air supply to the PPPE for the lab workers), the doors airlock system and any other essential services for the BSL-4.

  1. According to the relevant technical specifications and to the actual work requirements, the protection scope of the newly added UPS should include the air supply and exhaust system of the protection area, the life support system, and the low-temperature refrigerator for the bacterial seed library.
  2. One should reasonably determine the setting mode, capacity and battery configuration of the UPS, and verify the structural load for the newly added battery room.
  3. One should propose a reasonable modification plan for low-voltage power distribution system.
  4. There are fire-fighting water pipes in the new battery room that must be isolated and treated. Corresponding modifications must be made to other mechanical and electrical problems such as fire protection that existed in the transformation process.

11.4 Pneumatic automatic doors

Door seals

The tightness of the doors is extremely important for the safety of the laboratory as they must always maintain the right negative pressure gradient throughout the lab. When this pressure differential is working, the only lab air that may be released outside first has to go through a directional flow to a double stage HEPA filters. For this reason, doors seals have to be perfect and their opening and closing must always be monitored.

Wuhan BSL-4 Open Chemical Shower Door, during construction; The pillars of the biosafety level four : national biosafety laboratory, Wuhan (P4). Zhejiang Education Press, Hangzhou
  • CN210289567U ‘Emergency opening and closing door button device’.
  • CN209991213U ‘Automatic air-supplementing airtight door’,
  • CN110005949A ‘Emergency door opening and closing button device and door opening and closing method’.
Wuhan BSL-3 Door D36 to laboratory room
Wuhan BSL-4 Pneumatic Door Air Flow Diagram. red parts are related to the Patent . Source: CN110005949A

Door operation

Inside BSL-4 lab 1, in 2017 showing open door during lab work

11.5 Decontamination showers and air exhaust

Patent

Patent CN209960702U ‘Exhaust system for biological safety laboratory’ is a WIV patent that added a small fan in the exhaust system of the chemical shower room in parallel to the HEPA filters. The purpose of the fan is to keep negative air pressure and enable air duct loop disinfection in a closed loop with:

  • The secondary exhaust BIBO high-efficiency filter unit
  • The air supply HEPA high-efficiency filter unit
  • The exhaust air HEPA high-efficiency filter unit
Wuhan BSL-4 Differential Air Pressure (compared with atmospheric) and Flow Diagram, modified with the patent information. Source: patent CN209960702U Exhaust system for biological safety laboratory
Wuhan BSL-4 Chemical shower room; The pillars of the biosafety level four: national biosafety laboratory, Wuhan (P4). Zhejiang Education Press, Hangzhou
Wuhan BSL-4 Camfil HEPA Filters; The pillars of the biosafety level four : national biosafety laboratory, Wuhan (P4). Zhejiang Education Press, Hangzhou
Wuhan BSL-4 BIBO filters

11.6 Waste water treatment — continuous inactivation

Patent

Patent CN110040799A Continuous high-grade biological safety laboratory wastewater inactivation device is a wastewater inactivation patent published by the WIV in 2019.

Evaluation

Any addition of sensors, temperature changes and flow control represent potential hazards that need to be considered and examined. This patent is a major change of design and this raises the question of whether the hazard and operability study (‘HAZOP’) was redone or not.

Wuhan BSL-4 Waste toxic water inactivation treatment flow diagram. Source: CN110040799AContinuous high-grade biological safety laboratory wastewater inactivation device
Wuhan BSL-4 Waste toxic water tank

11.7 Wastewater treatment — descaling

Patent

Patent CN110015706A “Scale removal system and method for continuous biological safety laboratory wastewater treatment equipment” is another WIV patent that describes a descaling system for continuous biological safety laboratory wastewater treatment equipments.

Evaluation

Although the purpose of this innovation is clearly to improve the operational safety, it is again a major process change and as such raises the question of whether a proper hazard analysis was carried out before implementation.

CN110015706A Scale removal system and method for continuous biological safety laboratory wastewater treatment equipment
Example of Kansas State University ABSL-3, Toxic waste water Continuous batch sewage treatment device (one-use one-standby configuration). The pillars of the biosafety level four: national biosafety laboratory, Wuhan (P4). Zhejiang Education Press, Hangzhou
Wuhan BSL-4 Continuous sterilization equipment adopting remote control operation mode. The pillars of the biosafety level four: national biosafety laboratory, Wuhan (P4). Zhejiang Education Press, Hangzhou

11.8 Drain double pipe welding for contaminated water

Patent

Patent CN208058164U ‌”Double-layer casing for discharging live toxic wastewater in high-level protection laboratories” is a WIV patent which relates to the welded junctions of the double-layer biological live toxic wastewater discharge and treatment pipes for the BSL-4.

  1. There is no mature double-layer biological live toxic wastewater discharge and treatment pipeline technology for high-level biosafety laboratories in China.
  2. The current double-layer live toxic waste water casing in foreign countries is mainly welded, which requires very high welding technology, and the welding construction is often restricted by pipeline layout and other restrictions.
  3. The known foreign double-layer live toxic wastewater pipeline technology uses fixed internal supports for the pipelines, which have poor adjustment and movement capabilities. There is a leakage hazard at the welding or connection points.
  4. There is no mature technical strategy and implementation plan for the maintenance, disinfection and subsequent treatment of double-layer pipes.
  1. Butt welding is difficult and can cause deformation.
  2. Butt welding can cause problems that affect sealing integrity.
  3. Pipe supports are not flexible enough.
  4. It is difficult to carry out segmental repair or disinfection.

Evaluation

We note that by doing a fillet weld, the sealing ring 23 could be heated and damaged; the fillet weld is not solid enough and may crack, causing leak. Specifically the dilatation stress of changes from room temp to 135°C allied to vibrations could loosen the sleeve. This could damage the fillet welds to the point of cracks and leaks.

Wuhan BSL-4 patent for pipe in pipe for toxic water drain. Source: (Patent CN208058164U ‌Double-layer casing for discharging live toxic wastewater in high-level protection laboratories)
Pipe in pipe welding configurations; Explanatory simplified sketch of Wuhan Institute of Virology patented pipe in pipe connection, modification from butt weld to fillet weld with sealing ring
Wuhan BSL-4 toxic water pipe in pipe weld control (X-Ray and Liquid Penetrant test), Wuhan National Biosafety Laboratory Environmental Report (EIA) 2018 (Appendix 2)

11.9 Autoclave and air incinerator

Patent

WIV Patent Application number CN109966535A ‘Biological safety type autoclave and sterilization method’ shows issues with the original design.

Mark-up autoclave diagram: source CN109966535A Biological safety type autoclave and sterilization method
  • Temperature instability. To remediate temperature instability, the patent introduces a preheating jacket, plus a regulation of jacket and steam inlet pressure with a control valve.
  • There were initially two safety valves. Following modification only the jacket safety valve remains. This decreases the cost and removes a external environment risk from a false operation of the of the safety valve on the jacket.
  • The temperature sensor was initially fixed to the cavity and did not measure the temperature on the waste in the middle; the patent provide a temperature sensor that is to be inserted into the waste itself.
  • The patent reveals risk of cavity door panel sealing ring aging and leaks.
  • Instead of single chip microcomputer (no upgrade, detection limited) the patent upgrade with a PLC with detection function.

Air incinerator purchased in December 2019

It is worth noting that the patent does not show an air incinerator at the exit of the exhaust pipe of the cavity. Without an air incinerator, there is a risk of contaminated waste aerosol release. The air incinerator is an electric heating device that treats the exhaust of the autoclave sterilizer, so that it can be safely discharged.

12. Conclusion

Let’s visualize a brand new submarine that never sailed, with a new captain that has never served in a submersible, as part of a government vision to develop a submarines fleet with as much independence from foreign manufacturing and parts as possible. Blueprints for a well proven submarine design are purchased from France, while the actual construction is done by a local company and is used as a test-bed for local technologies. For instance the engineers opt to modify the various sealing systems. They also find the pipes difficult to maintain so modify the welding connection; meanwhile, there are power instabilities, so they also decide to redesign the battery room, and so on, some of it half way through the construction of the submarine.
How safe would that vessel be?

  • Have all these modifications been properly run through hazard analysis and mitigations?
  • Have the issues encountered been adequately solved, such as the power instability (that resulted in an upgrade of the UPS), or the pipe welding issues.?
  • Is the final lab design and build safe, both in terms of technical solutions and in terms of processes, such as adequate operations and maintenance?
3D view of Wuhan BSL-4 core laboratory floor. (yellow are the showers

Annexes

Annex 1: WIV Bidding table 2017–2022
Annex 2: Wuhan National Biosafety Laboratory Environmental Report (EIA)
Annex 3: Wuhan Patent List and China biosafety lab publications
Annex 4: WIV Tenders & Contracts 2017–2021
Annex 5: WIV Schedules

Related DRASTIC research

Medium Articles:

Notes

[1]: For an explanation of Farmer’s graph and its application to nuclear energy decision making, see ‘Treatment of uncertainties for security-related design aspects of advanced reactors when using a risk-informed licensing approach’, Idaho National Laboratory, Sep. 2021. That paper is also a great introduction to risk-informed decision making and quantitative modelling approaches used in advanced nuclear reactor licencing.

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Opinions, analyses and views expressed are purely mine and should not in any way be characterised as representing any institution.

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Gilles Demaneuf

Gilles Demaneuf

Opinions, analyses and views expressed are purely mine and should not in any way be characterised as representing any institution.