Wuhan BSL-4: Engineering Review

Gilles Demaneuf
46 min readMay 28, 2022

Research by the DRASTIC collective

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.

A submarine is a maximum containment cylinder. Its survival entirely depends on keeping the water outside within safe dive parameters. From an engineering point of view the hatches, the overall design of the shell, the quality of the metal sheets and of the welding, also the quality of the multiple pipes and valves and the design and construction of the multiple junctions where the containment envelope is traversed by pipes or cables, are all essential pieces of engineering in a high containment lab, just as they are for a submarine.

Still, there is one major difference. While some of the engineering challenges may be similar, maximum containment laboratories (BSL-4) operate in reverse: the main objective is to isolate the the external environment from any pathogen that may be stored and worked on inside, with many more people potentially at risk (possibly the whole population).

1.2 Nuclear reactors

Maybe a better analogy would thus be with radioactivity containment.

For a nuclear reactor, essential design choices and human processes are required to minimize a possible release of radioactivity by the occasional technical failure, human error or external event such as an earthquake, flooding or plane crash, however unlikely each individual event may seem.

There is simply no room for complacency, first because the possible consequences of a melted core on the populations and economy can be enormous, but also because over many years of operations and many reactors in the world known individual risks quickly accumulate in a non-negligeable total (10 years x 200 reactors is a sizeable x 2,000 factor from one reactor-year), while unknow ones may eventually hit.

The pioneer in nuclear reactor design and safety was the US Navy, which under the guidance of Admiral Rickover successfully ran a fleet of submarine propulsion reactors then used its experience to help design the first commercial nuclear reactors. Unfortunately, or maybe predictably, commercial incentives of this civilian application combined with an energy crisis (the 70s) soon resulted in serious regulatory and corporate shortcomings exposed by the Three Mile Island (TMI) accident.

Since then the US regulatory oversight has greatly improved with particular attention to avoiding economic or political capture. In the US at least transparency of evaluations of nuclear operators now play a key role while risk-informed design pervades all new developments. The risk-informed approach relies greatly on detailed probabilistic evaluations backed by databases of past events, which itself requires transparency and sharing between operators, facilitated at the national (INPO) and international level (WANO, INSAG).

In that process very clear guidelines are set as to acceptable risk limits, expressed as radiation dose at exclusion zone boundary vs.event frequency.
Here is a typical Farmer’s graph [1] for risk-informed reactor licensing:

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.

Developing countries (China and India being the most important) may not have yet internalized this.[2]

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).

Additionally the maturity level of BSL-4 laboratory risk-informed design, probabilistic evaluation, operation and transparency seem to be markedly inferior to the one applicable to nuclear reactors anyway, while the risks in human lives from a containment breach may be at par.

Compared to the nuclear enterprise, there is indeed a real lack of proper risk-evaluation (some a-priori ‘very unlikely’ seems to be as far as many quantitative risk evaluations go), very fuzzy operational risk limits, poor control of human factors, limited budgets, limited transparency (if any in some countries), perverse pressures to publish which may favour risky experiments, and common regulatory capture (reminiscent of the NRC before TMI).

To be clear that immaturity in the biocontainment domain is not exclusive to China and is actually a more general problem of weak institutions governing the design and operation of biocontainment labs (particularly international) which rests in part with developed countries showing themselves a lack of leadership on the international stage and of transparency at home, while the Chinese social, cultural and institutional contexts contribute to make this bad situation potentially worse there.

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

Soon after its signature, multiple SARS Lab Acquired Infections at the then very top BSL-3 laboratory in China, culminating with the Beijing — Anhui outbreak of April 2004, confirmed strong local biosafety carences that would have to be remediated.[7]

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.

Practically,

  • 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.

The objective and the way it was implemented was clearly laid out by Song Donglin, Director of the BSL-4 project office, in an interview entitled ‘Create an “Aircraft Carrier” for Virus Prevention and Control’ (12 April 2018, Guangzhou Daily):

“The ravages of SARS caused the Wuhan Institute of Virology to receive the task of building a P4 laboratory under the circumstances of almost ‘three nos’: no equipment and technical standards, no design and construction team, and no doctoral supervisors and experience.
[..] At that time, there was only the P3 laboratory established by the Academy of Military Sciences and the Import and Export Quarantine Department after absorbing foreign experience. The standard was not high, nor was it normative. The cutting-edge national scientific research team there also had a laboratory infection accident while studying the SARS virus. [7]
[..] Knowing nothing about the laboratory structure, biosafety protection system, etc., and even not being good at design, site selection, and construction, the laboratory team produced an Environmental Impact Assessment report within three months. And the deputy director of the Institute of High Energy Physics of the Chinese Academy of Sciences who undertook the large science project of the electron-positron collider said, ‘You guys are so daring, you take over the task with your eyes in the dark.’ ”

[..] As a major participant in the construction of China’s first P4 laboratory, Song Donglin is unequivocal:

“100% of the key equipment is imported. Biosecurity should be built on a mature, experienced and reliable foundation. and technical solutions that have not been time-tested cannot enter the laboratory. To improve safety, imported materials are used in sewage treatment equipment, inflatable airtight doors, air conditioning systems, air ducts, maintenance structures, and even sealing elements and floors.”

[..] In order to “prevent foreign countries from suddenly choking our necks” Song Donglin undertook the project research of the localized model laboratory [5]:

After two years of layout, the current model laboratory (simulation exercises, equipment, and no real pathogenic research objects) can reach 80% localization, but it cannot be used immediately. It is necessary to strengthen quality and safety, and [only] partially replace imports.
[..] Referring to the foreign training system, the laboratory has formed a green-orange-red three-level induction system. After reaching the corresponding level, you can enter the laboratory to do research. At present, only 10 people have obtained the qualifications (for scientific research activities). And there is not a single red level researcher (level at which one can carry out research and training independently). We are still helping and learning from each other.”

On that path towards full technology autonomy, the contracting of the Wuhan BSL-4 design to France and the purchase of foreign equipments were both necessary to access or validate some technology. For the Chinese side the cooperation with France was conceived as an apprenticeship that would be useful not only for the Wuhan BSL-4 but also for the other BSL-4 labs being constructed at the time (Kunming) or planned (Harbin). [15]

As the 3rd pillar of the ambitioned MOU shows, there was a strong Chinese need to to better understand certification processes and develop a missing necessary domestic legal and regulatory framework. [3]

As far as the 2nd pillar is concerned (personnel training), China learnt from other top BSL-4 operators too: training was also received from Australia and the US, not only for the future Wuhan BSL-4 operators, but also for future BSL-4 operators at Kunming BSL-4 with some training in 2012–13 via Galveston (under a DTRA program).

Construction of the future Kunming BSL-4 was by that time actually a bit ahead of the of the Wuhan BSL-4 due to the glitches and delays in the cooperation with France there, as we explain in section.

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.

Beyond some (limited) immediate economic benefits of the project, the French government expected further economic engagement with China — Wuhan being already a main French entreprenarial base within the country.

But most likely the main calculation was that on the international scene the project would offer some prestige and help position France as a responsible state finding its own way, even if (or especially if) that meant standing up to the US. Indeed, at the time of the signature of the MOU (Jan 2004), the US had just been in a damaging open conflict with France on the occasion of the 2nd Iraq war (2003).

As a result, the US opposition to France transferring BSL-4 technology and know-how to China would fall mostly on deaf ears at the French governmental level, while it carried more weight with the French intelligence services [13]. These intelligence services concerns may effectively have been sidestepped as to the French decision to take on the project, but they were never fully sidestepped during its execution, resulting in tensions on the French side.

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.

By 2008, 4 years after the launching of Wuhan BSL-4 program, China had produced the following major changes, which went some way towards demonstrating some design and engineering localization:

Main differences between the Lyon BSL-4 reference and the Wuhan BSL-4

The main Chinese innovations in the above table are:

  • 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

We note that reviewing and if necessary altering the software of the Siemens control system could be expected for cybersecurity and to avoid any intel backend access to the digital ‘brain’ of the BSL-4.

Other Chinese innovations also include several improvements (some patented) such as an increase of the performance of the UPS (Uninterruptible Power Source) to address power instability, some modifications to the pneumatic doors, some modification of the chemical showers and air exhaust, some modification of the water treatment etc, which together cover most of the important features of the lab.

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

FOAK is key concept in complex engineering, particularly in relation to the development and certification of complex projects such as nuclear power plants were failure must be absolutely minimized, due to the huge potential consequences.
A FOAK project introduce may risk with new technologies and new processes, both during construction and operation. For instance even the best designed and planned nuclear plant based on a new technology will need hardening and validation through actual construction and operation.
The same to some extent applies to high containment biosafety labs. An FOAK project in that domain is normally something that is very carefully planned and requires plenty of existing experience to have the best chance to catch and solve issues as they may develop.

Hence aiming for a technology FOAK on what is at the same time a country FOAK may seem particularly risky.

However please note that China had tested some of these technologies on a model laboratory for up to 10 years via its research facilities in Tianjin , and may have had some construction and installation experience with these in Kunming (without official certification at that stage, so we can only speculate on any operational experience).

Hence it is actually quite possible that China was able to limit some of that FOAK technology risk by drawing from some not well publicised previous domestic experience. This would certainly explain what would otherwise look like a very risky choice.

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 project faced a rather predictable clash of objectives, experience and complex-project management culture:

  • 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.

As a result of these differing objectives and contrasting ways of managing complex projects (and not helped by repeated concerns within French intelligence services), the French side eventually took some distance from what looked increasingly to some as a rather difficult engineering project with less and less control on the final delivery [12].

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:

The construction and maintenance of the P4 laboratory is complex and has high technical requirements. China has no experience in the construction and maintenance of the P4 laboratory. Appropriate and limited international cooperation is necessary

[..] In the framework agreement [between France and China], it is proposed that the ‘four wheels’ of scientific research cooperation, personnel training, laws and regulations and standards, and laboratory construction should be synchronized around the P4 laboratory in the cooperation between China and France, which makes the laboratory construction susceptible to changes in the Sino-French cooperative relationship.

A ‘three no’ institute without its own state key laboratory, academician, or even no doctoral supervisor before 2003, has to build the first P4 laboratory in China and even in Asia (although Japan has a P4 laboratory, it has has not been run at P4) — it will inevitably be dubbed the ‘little horse-drawn cart’. An institute with a body of less than 200 people has received the joint attention of the heads of governments of China and France, and is active on the international academic stage , and will inevitably be ridiculed as ‘little head wears a big hat’.

Although unharmonious voices have been heard from time to time, the Wuhan Institute of Virology has firmly established its own beliefs, and what has been started can’t be stopped. It has continuously eliminated the conflicts caused by the different concepts and cultures of the two countries, and has overcome resistance and difficulties from all aspects.

On June 28, 2004, Chen Zhu, then vice president of the Chinese Academy of Sciences, clearly instructed Wuhan Virus Institute: [..] Cooperation should be carried out based on the principles of friendly cooperation, accepting there that differences between China and others, prioritizing ourselves, and seeking truth from facts [14].

Afterwards [after Oct 2004], the Chinese delegation conducted extremely difficult negotiations with representatives of RTV Company in Lyon on the design and construction cooperation framework and technical issues of the P4 laboratory, and finally persuaded the French side to accept the proposal, that is, it must be in accordance with Chinese laws and regulations.

[..] The cooperation of the Wuhan laboratory construction project only involves the core laboratory part. In the core laboratory part, in order to make its design better conform to Chinese standards and facilitate the later maintenance of the laboratory, the French company does not participate in the cooperation in the form of general contracting. The French company is responsible for the conceptual design of the laboratory, and the Chinese company is responsible for the laboratory itself. The French engineering management company cooperated with the Chinese supervision company to control the quality and progress of the project construction. The Chinese company is responsible for the construction of the laboratory, which is coordinated by the Wuhan Institute of Virology as the owner.

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.

The WIV main offices and labs, including animal rooms and BSL-3, were located at its original WIV site in Wuchang near the Chinese Academy of Science in the centre of Wuhan. During the feasibility study it was decided to localize the new laboratory complex — with its BSL-2, 3 and 4, animal building and research center — to a semi-rural site in the south of the city (Zhengdian). The chosen site was right next to the Sinopharm Wuhan Institute of Biological products (WIBP, Vaccines) so as to build a full platform; from virus collection, preservation and studies to vaccine research and production. [4]

Note that the new research and lab complex in Zhengdian is called the Wuhan National Biosafety Laboratory. The WIV Wushang site is not included under that designation.

5.2 Layout

WIV — Wuhan National Biosafety laboratory, and comprehensive research center, Zhengdian Gold Industrial Park, general plot plan for environment permit

The Wuhan National Biosafety laboratory was built in three main phases:

  • 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

Note that the WIV researchers always had access to the existing BSL-2 and BSL-3 labs on the original WIV site in Wushang, as well as to the research centre there. A WIV shuttle takes the researchers between the two sites (a ~35 minutes commute).

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

These last adjustments occurred after the completion of the BSL-4 construction (2015) and during commissioning and operations, 2017 to 2019. Some of these resulted in patents application. (WIV patents are listed in http://www.whiov.cas.cn/kxyj_160249/kycg_160251/zlqk_160256/ and in Annex 3)

These modifications are also described in Appendix 1. Below chart is an extract for second semester 2019.

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].

The lab was eventually accredited in 2017 by China National Accreditation Service for Conformity Assessment (CNAS) based on the Guo Biao 19489:2008 standards (the Chinese national standard formulated in 2008).

The WIV did a standard comparison of the standards, but it did not update its standards to incorporate European ones. So we do not know how the lab meets European standards.

This transition between standards between initial design, construction and then certification, can generate a risk. Although this difficulty was most likely taken very seriously by all the parties, in its 2018 article “Quality management in a high-containment laboratory”, the WIV recognized the difficulty to integrate all the different domestic and international standards and guidelines and stipulates:

“Therefore, there is a real need for drafting a new standard or guideline specifically for containment laboratories”.

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.

The next accreditation stage for the WIV would be to be designated as a WHO Collaborating Centre for Surveillance and Research on emerging infectious diseases, so as to be included in international research coordinated by the WHO on emerging viruses.
This has not yet happened despite multiple pleas.

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

As we can see on the layout below, on the right side (east) the two suites lab symmetry is broken to create an additional small animal cell culture lab (Lab3).

Wuhan BSL-4 core lab layout — WIV

Effectively the Animal Room 2 with its shower and PPPS room (for putting on and removing Positive Pressure Protective Suits) has been rotated 90° clockwise, to open the space for the Lab 3 just above.
That Lab 3 is a small cell culture lab. With their shared PPPS room, shower and especially animal room, Lab2 and Lab 3 function more like a unit and cannot be truly isolated from each other.

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

Additionally the disinfection room N2 has 5 doors for a small surface (compared with 4 for N1), so that the doors take up nearly all the space in the room. This particular arrangement of multiple doors in a small surface area could create weak points in the structure given that the doors are relatively heavy stainless steel pneumatic doors.

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.

A few laboratories use stainless steel, for example the Bernhard Nocht Institute for Tropical Medicine (BNI) in Hamburg and the Robert Koch Institute BSL-4 in Berlin.
Most laboratories are instead made with concrete shell to provide heavy stiff construction, with urethane or glue type walls that are not subject to corrosion and are stable and easy to clean. For instance the Lyon BSL-4 laboratory uses a system of steel faced urethane panels approximately 5" thick, joined with silicon sealant and cam action locks. [6]

The Chinese side chose to innovate by using stainless steel sandwich panels, via an in-house development project, as per a study from the PLA Medical Support Technology Institute in Tianjin and the Harbin Veterinary Research Institute that has an ABSL-4: “Research and development of airtight biosafety containment facility for stainless steel structures (March 2019 Journal of Biosafety and Biosecurity”). The aim of the study was to investigate the sealing technology of stainless steel structural airtight biosafety containment.

The WIV BSL-4 used laser welding, floor junctions, corners, pneumatic doors, cable and pipes wall penetrations, and all equipment and structure of the lab appeared to provide adequate airtightness. The labs are kept at negative pressure, and the pressure gradients between the rooms (including showers), are monitored by a control system. In case of insufficient gradients the control system triggers an alarm.

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.

Most disinfectants contain chlorines. In a sufficient concentration, chlorines may corrode stainless steel by a process called pitting,which can appear easily where there is slight surface damage or localized stress. This may eventually eventually affect the pressure gradient of the lab rooms, which is the main defense against leakage. Liquid effluent could also potentially escape from the lab, in corners and other floor level folds susceptible to corrosion, and make its way out of the containment. It is not clear whether the switch to stainless steel containment was entered in the HAZOP (hazard and operability study) of the lab.

We know from sources that the stainless steel panels of the decontamination shower were indeed damaged by incorrect cleaning with sodium hypochlorite in early 2016, requiring repairs [12]. Through FOI’d emails, we also know that, soon after, Yuan Zhiming, the WIV BSL-4 director, asked in 2016 to an American colleague advice on which disinfectant(s) to use in various situations (email to Jens Kuhn NIH NIAID dated 15 July 2016). In the email, Yuan Zhiming mentions corrosion of pipeline and waste water equipment, so the stainless steel walls could also have been an issue.

FOI’d emails

Microchemplus is specified in the WIV environmental report annex 20. The environmental report shows an acceptable release of chlorines. The measures are taken 4 times in a working day; with a minimum measurement of 0,02 mg/L, but three samples out of 4 in the day have the exact same measurements: 0,41 mg/L. In such cases, it would have been correct to require counter measurements.

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.

The operational procedure changed from using formaldehyde fumigation to hydrogen peroxide H2O2. Hydrogen peroxide H2O2 is not corrosive, however it is unstable. Depending on the conditions of the environment it can decompose in water H2O or oxygen, which itself can be very corrosive. Vaporized hydrogen peroxide (VHP) is produced by the vaporization (depending on the the process, between 60°C and 130°C) of liquid hydrogen peroxide mixed with water. For sterilization without risk of corrosion, i.e. for prevention of condensation H2O2/H2O vapor, temperature, humidity and pressure shall be monitored.

Thus, depending on the sterilization cycle steps, until hydrogen peroxide decomposition, risk of corrosions could appear if improperly monitored. WIV also made a special system to make the sterilization process in the air exhaust ducts (see patent CN209960702U, Exhaust system for biological safety laboratory).

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)

China also developed its own manufacturing network for HEPA BIBO filters, life support systems, stainless steel sandwich panels and structure, based on research by the Institute of Medical Support Technology (Institute of Systems Engineering) Academy of Military Sciences in Tianjin.

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).

At the Wuhan BSL-4, the laboratories are kept at a differential of -90 Pa, the chemical shower room at -75 Pa, and the changing room at -50 Pa, all forming a proper gradient that always pushes the air towards the core of the lab. [In the same way the BSL — 4 suits have a positive pressure differential, pushing the air out of the suits so that pathogens do not get in.]

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”).

Among many other systems, the control system also supervises the airlocks, so that as in no case an airlock room (for instance a chemical shower room) has two doors opened at the same time. Having two doors opened at the same time would annihilate the airlock and open a route for airborne pathogens to leave the laboratory rooms. In case of any unexpected reading (any issue with the pressure gradient, unexpected unlocked door, etc..), the control system may trigger an alarm.

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

If the control system crashes at any time, all these automatic safety checks and automatic adjustments may fail, creating a dangerous situation. To avoid this scenario, the control system is provided in fully hot standby dual machine mode, meaning that if one system crashes, a second one is ready to take over immediately exactly where the first one stopped working.

The WIV BSL-4 control system was supplied by Siemens. It was commissioned with a higher than standard sampling rate, for a finer control of the pressure differentials. In a 2018 article (A record of the construction and research team of the P4 laboratory of the Wuhan Institute of Virology), Zheng and Li explain:

“The PID parameter tuning is either 2 seconds or 0.5 seconds sampling, Siemens followed our recommendations during the commissioning.”

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:

Regarding the work unit control interface provided by Siemens, Tong Xiao, deputy director of the project office, thought that the back-end interface was not suitable, so he designed a new interface by himself.

The changes to the algorithm are more obscure and difficult to interpret. Zheng & Li explain:

It draws on the French dual-machine hot-standby technology, its specific control algorithm and balance point, starting frequency and mathematical model of the control loop are all explored in practice by our side, and the dual-machine effect is achieved with an innovative model. The self-set automatic control mathematical model achieves a more stable pressure difference control effect.

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.

For instance why was a ‘more stable pressure difference control’ required?
If the system was based on Lyon BSL-4, why take the risk to try to improve a system that has 10 years of proven track record in France?
What was indeed China’s experience about negative pressure control for BSL-4 labs that could point to the need of such improvement?

These are many questions that WIV could easily clarify. One strong possibility is that China had already acquired some experience of these issues in its Tianjin model lab and in the Kunming BSL-4 (quite possibly via test runs without pathogens, or with much safer pathogens). In that case it would indeed aim to quickly roll out that algorithmic control experience onto the high quality Siemens hardware.

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.

The WHO list the following type of extinguishers:

Extract Laboratory biosafety manual. (3rd edition)

Whatever extinguishing agent is used is used to fight a fire in a BSL-4, the resulting liquids and slur may be contaminated by biological agents. These must be retained before decontamination, which calls for the right tank capacity (especially if using liquid extinguishers).

The WIV chose heptafluoropropane (FM-200) as extinguisher agent, a type which is not included in the World Health Organization Laboratory biosafety manual. 3rd edition (2004). The WIV also designed the extinguishers nozzles so as to avoid overpressure and release of contaminated gas.

In their 2018 article, Zheng & Li explain:

“Traditional fire extinguishers in our country use heptafluoropropane fire extinguishing agent, which is usually sprayed out as soon as possible during fire fighting. This is contrary to the basic requirement of P4 laboratory to avoid positive pressure.

We and fire equipment suppliers have tested and ensured that in the case of the fire extinguishing agent flow, the innovative design of the fire extinguisher nozzle mode makes the release of heptafluoropropane in a controllable state, which not only meets the negative pressure requirements of the laboratory control system, but also achieves a good fire extinguishing effect.”

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.

After using this fire extinguisher agent inside the BSL-4, WIV would thus have to:

  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.

All of this would also to be included in the HAZOP (hazard and operability study).

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

“In the Wuhan BSL-4, the core pieces of equipment are connected to the UPS: the airtight doors and chemical shower control cabinets, direct digital control cabinets for ventilation systems and backup exhaust fans, biological safety equipments [check] , animal isolation cages, and protection area lights.
The output of the two sets of battery packs are monitored in real time by the central monitoring system to ensure uninterrupted effective operation of the power supply.”

(Extract from: The pillars of the biosafety level four : national bio-safety laboratory, Wuhan, Zhejiang Education Press, Hangzhou 2018).

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.

Grid power instabilities and potential lightning strike surges issues noted during trial operations (in 2017 and 2018) resulted in a the decision to reinforce the UPS system in 2018.

As per a summary published at the time:

In order to improve the laboratory biosafety assurance capability and solve the interference of the external power supply quality and lightning voltage surges on the safe and stable operation of the laboratory, it is proposed to add a set of UPS systems to equip all biosafety equipment with UPS power supplies.”
(2018–04–16, Chinese Academy of Science, Wuhan National Biosafety Laboratory).

The WIV decided to the UPS system and add a new battery room as follows:

  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.

As a result, an additional UPS capacity with new batteries that could power additional essential systems was installed between end 2018 and beginning 2019. This work was complex and covered the additional UPS power system and all required electrical connections, the battery room extension, isolation of water pipes there, and other necessary modifications of the electrical power system (see UPS power distribution renovation project of P4 laboratory building of Wuhan Institute of Virology, bid ZB0109–1808-ZG1092, for 1,3 millions Yuan).

We note that the extension of UPS does not fully solve the voltage instability and lightning surge problems that were noticed in 2017–18 and led to these changes. However, the risk was mitigated by the extended battery room to power essential systems necessary to maintain the maximum containment of the facility. One constraint though would be the limited duration of the battery power before power needs to be reestablished.

For the record there were serious lightning events in summer 2019 (31 Jul-1 Aug), after the UPS upgrade (see Weather meteorological data 31st July 2019)

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

Pneumatic doors require significant maintenance. The WIV BS-L4 doors are pneumatically sealed but are not the “handwheel” types which are safer but less practical to handle. The doors at the French BSL-4 Lab in Lyon are also pneumatic, but are constructed from solid plastic, instead of stainless steel, which makes them easier to operate.

There are 52 pneumatic automatic doors to manage, maintain and operate in the WIV BSL-4 Laboratory. The WIV published 3 patents concerning pneumatic doors for BSL-2, 3 & BSL-4 laboratories:

  • 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

The patent CN110005949A aims at maintaining air pressure in the pneumatic seal of the door. Instead of continuous pressure, air is injected when a sensor detects that the pressure is below a certain level, and an alarm is activated in case the system suffers damage:

The invention monitors the gas pressure in the door sealing strip in real time, and automatically completes the air addition work when the pressure in the sealing strip is too low, so that the pressure of the door sealing strip is always above the set value. It ensures that the air-tight door is always in an expanded tightly sealed state, which solves the problem of natural decline in airtightness of the air-tight door.”
(ref: Patent: CN110005949A )

Wuhan BSL-4 Pneumatic Door Air Flow Diagram. red parts are related to the Patent . Source: CN110005949A

To illustrate the utility of the patent, WIV highlighted the following possible problems:

The gas supply tube is bitten by rats and the sealing strip is ageing and damaged, both of which are damaged, resulting in special leakage”.

“After the airtight door is closed, the door seal is inflated and swollen for a long time in a closed state. In actual use, the air path will be slowly released. Insufficient pressure in the door seal will reduce the expansion and sealing performance, and there is a possibility of air circulating between adjacent rooms”.

“The door sealing strip represents a risk of leakage between the two rooms”.

The continuous purging of space and air volume for a long time will aggravate the rupture of the damaged seal”.
(ref: Patent CN110005949A )

WIV states that the invention will prevent existing problems from occurring (leakage), and provide alarm in case of problems:

The present invention can automatically supply air at intervals, which is both preventive and a temporary protection, and will output a fault alarm prompt to remind the Personnel to check and repair to reduce the possibility of potential leakage in the room.”
(ref: Patent CN110005949A)

Door operation

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

The photo above, taken in one of the Wuhan BSL-4 lab suites, points to some incongruity. Normally the chemical shower door should be kept closed. If the door is instead left open, aerosol pathogens have plenty of time to enter the shower room. If anyone in the changing room (PPPE room) subsequently opens the chemical shower unit door before it had a chance to be decontaminated, the released pathogen could then contaminate anyone who enters that space and also the PPPE room that person is coming from.

Although this photograph was taken in 2017, while the WIV BSL4 was still in the trial stage until it became officially operational in January 2018, it sits at odds with best safety practices. It also raises questions about the control system that should raise an alarm in this kind of situation.

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

The fan can be regulated with a manual valve accessible in the shower room. The small fan capacity is about 16% of the air volume passing through the HEPA filters.

The WIV patent explains that this innovation is useful to reduce or eliminate the risk of positive pressure in case of control system failure, exhaust fan failure, antifreeze failure, fire protection failure, etc… and that it effectively solves the “problem of disinfection” of the ventilation pipe.

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

In Patent CN209960702U the WIV revealed that there were certain airflow interferences in the chemical shower room, which led to “severe challenges” to the negative pressure control program of the chemical shower room. In the patent the WIV also stated that it had similar problems before with their P3 laboratory biosafety cabinets, fume hoods and exhaust regulation of animal cages.

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

We also note that the WIV requested bids in September 2019 for a renovation project of the BSL-4 central air conditioning and for its environmental air disinfection treatment system was (ref WIV bid transaction ZB0109–1909-ZCHW0913 and OITC-G19033097 in Appendix 1).
This seems to indicate issues with the just finished and certified BSL-4.

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.

There are two waste water methods, continuous and sequential, with sequential being batch based heating with inactivation at 140°C during a minimum time, while continuous inactivation involves the flow of water in a heated environment for enough time to ensure inactivation. (ref. Patent CN110040799A)

The WIV patent states that both methods have their risk: continuous inactivation can lead to pipe leakage (due to pipe length issues), while sequential is sometimes not practical and may not fully ensure inactivation.

The object of the WIV invention is a continuous high level of biosafety laboratory wastewater inactivation, with the claim that it “greatly reduces the biological risk in the inactivation process, and effectively guarantees the reliability of the equipment”. The invention also discloses a continuous high-grade biological safety laboratory wastewater inactivation method. The invention can continuously treat the wastewater in the wastewater collection tank. The inactivation method is to first use clean water to test whether the inactivation conditions meet the requirements.

The WIV patent relies on two steps: first stabilize the inlet water, by mixing wastewater with regular tap water, and heat it to 95°C, then pass the flow of water through a coil heater for not less than 20 minutes. The WIV claims that this solves the design flaws of their actual continuous and sequential system.

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.

The WIV patent explains that organisms which have been inactivated by high temperature tend to adhere and pile up on the electric heater and the surface of the pipe insulation unit. This in turn results in significantly decreased flow and even some blockage of pipes, meaning that the continuous operation of the water treatment system cannot be effectively guaranteed.

The patents says that the invention is effective in preventing acid and alkali washing from damaging the sterilization pipeline during the descaling process. The patent also introduces PH measurement to ensure long-term stable operation of the equipment .

The invention can effectively remove the scaling deposits within the electric heater and at the same time, by monitoring each alkali wash (measure of the pH value) avoids pickling [acid corrosion] that may cause equipment failure and damage to the sterilization pipeline during alkali cleaning.
(ref: Patent CN110015706A Scale removal system and method for continuous biological safety laboratory wastewater treatment equipment)

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.

For example, are the PH measurements sufficiently reliable? Could there be any operational issue introduced by the added complexity of a PH sensor and its potential failure or mis-reading?

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.

The patent lists the following problems in the existing wastewater double pipes:

  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.

To overcome the above issues, the patent provides telescopic radial supports with springs supports for the inner part, and connection of pipes by pressure, grooves with seals, and then a fillet weld, instead of butt welding. The rationale for the changes are:

  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.

Pipe design calculates the necessary supports and optimal routing, with loops, sliding or fixed supports, depending on stress analysis and thermal expansion.

However, although sliding or spring support may be necessary in some parts depending the analysis, replacing supports by spring support system systematically could cause instability of the inner line.

The patent considers butt welding stainless steel pipe as “difficult”. The weld is special and requires high standards procedure and welder qualifications. It is part of a construction and maintenance qualification plan. It requires great care before changing or lowering the weld junction procedure to fit lower qualified welders.

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.

We consider that it would be better to use butt welding to avoid both the sealing ring and the fillet weld, and to provide a better junction.

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

In particular fillet welds have proven to be prone to vibration-induced fatigue cracking. For system subject to vibration, it is definitely preferable to use butt welds. Vibrations are prone to happen as the WIV patent includes radial spring support between the two pipes.

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

The patent lists these following biological risks and provide solutions to reduce them:

  • 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.

The WIV eventually purchased an air incinerator in December 2019, from Yanneng Electrical Heating Equipment.

See Announcement of consultation on procurement of air incinerators and testing services by Wuhan Institute of Virology, Chinese Academy of Sciences Project Number: ZB0109–1911-ZCHW1229 budget of 320,000 yuan.

The incinerator is a box structure, which is installed on the exhaust pipe outside the inner cavity of the sterilizer to realize the incineration treatment of all the media discharged from the inner cavity. The principle is to heat the filled high-temperature resistant material through an electric heating rod to form a local high-temperature environment ( between 380 ℃ -450 ℃ ) . The aerosol exhaust gas generated during the sterilization process is subjected to high-temperature treatment in the incinerator and then safely discharged.”
(Project Number: ZB0109–1911-ZCHW1229)

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?

While the risk for a submarine is for those inside it, for a BSL-4 lab the risk affects the outside environment — and that is potentially all of us. In the case of the Wuhan BSL-4, the Chinese engineering team changed the containment structure to stainless steel, changed the door seals, the air control system, the batteries and many other features, all despite never having operated such maximum containment lab.

In the case of the Wuhan BSL-4, the acquisition of both a technology and a country first-of-a-kind has inherent risks.

The numerous design change may have been motivated by intended technical improvements that could also help eventually secure independence from foreign imports, and may also have been facilitated to a certain extent by whatever local knowledge China was able to develop, be it on model labs in Tianjin or possibly in the construction of the Kunming BSL-4.

These changes should nevertheless raise three questions:

  • 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?

With regard to the last point above, its is worth noting that beyond technical specifications, the reality of management and operation of a BSL-4 can easily fall behind the required highest standards, especially in a country with limited experience and structural disadvantages (no transparency, little incentive to speak up to authority, no public pressure, potentially confused management with a dual structure involving the party).

Errors in design and construction, weak management and weak risk culture can have worldwide impact both with nuclear power plants and with high-containment labs.

The nuclear industry learnt it the hard way, and has in answer tried to strengthen not only domestic but international norms, with at least some partial success [8]. The confused conception and delivery of the Wuhan BSL-4 and the limited knowledge we have of Kunming and Harbin BSL-4s are not ideal. Unfortunately they are no exception either in a growing field that is subject to so little hard scrutiny that no public record of BSL-4s in operation worldwide exists, without even talking about BSL-3s.

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:

Presentations:

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.

[2] For a very relevant discussion of risk tolerance standards concerning U.S. nuclear heads (the Walske rules), a history of regulation of U.S. civilian nuclear enterprise pre and post Three Mile Island and the complex challenges of international regulation and cooperation in nuclear energy projects, which all offer interesting parallels to maximum biocontainment labs and activities, see ‘The Nuclear Enterprise’, based on a conference organized by the Hoover Institution at Stanford in Oct 2011.

[3] Understanding Certification processes may have been just as important to the Chinese party as some of the technical knowhow. In China it is not unusual for some project to start coming off the ground before even official authorisation, and to come into production before official certification. For instance in 2010 more than twice the officially authorised number of nuclear power plant projects were past their prefeasability study phase, including two projects in preliminary work (Rushan and Jiujiang) without the required approval of China’s National Nuclear Energy Safety Agency (NNSA), forcing central authorities to belatedly step in. Exactly the same issue happened in the following years with many BSL-3 labs being built as prestige projects, run without authorisation and without well thought-out budget.

[4] For more details, refer to Wuhan Institute of Biological Products Co, and Biological Laboratories in Wuhan and their roles in coronaviruses research.

[5] One cannot fail to note the nationalistic tone of the “prevent foreign countries from suddenly choking our necks”. As to the title of the article (“Create an ‘Aircraft Carrier’ for Virus Prevention and Control”), the militarist vocabulary certainly complements the strategic goal of full independence from importers.

[6] ref. Journal of the American Biological Safety Association, 4(1) pp. 24–32 © ABSA 1999- designing the BSL-4 laboratory Chapter 9.

[7] For more details about the 4 primary infections at the CDC NIVDC in Beijing and the resulting Beijing-Anui outbreak in early 2004, see https://gillesdemaneuf.medium.com/the-good-the-bad-and-the-ugly-a-review-of-sars-lab-escapes-898d203d175d

[8] In the US the reshaping of the Nuclear Regulatory Commission (NRC) post TMI is largely considered as a success, as is the Institute of Nuclear Power Operations (INPO). The international effort to share knowledge and strengthen norms has been more patchy, but the World Association of Nuclear Operators (WANO), the International Atomic Energy Agency’s International Nuclear Safety Advisory Group (INSAG) and the World Institute for Nuclear Safety (WINS) have been reasonable attempts in that direction.

[9] Gabriel Gras, a French biosecurity expert attached as a technical expert at the French embassy worked with the WIV until its certification in 2017 and left thereafter to become Gopura Asia China CEO between February 2017 and march 2018. Gopuras Asia was formed by Thierry Morand, the ex president of Clima Plus, which worked on the Wuhan BSL-4 until its bankruptcy and liquidation in 2017–18.
René Courcol was on paper still working on biosecurity and biosafety at the WIV in 2018, making him the last French representative in that project. His actual authority and precise role was not clear, but in 2018 he wrote the article on Chinese standards mentioned earlier (published in 2019 in the Journal of Biosafety and Biosecurity). He seems to have left Wuhan shortly after and is now working for a Expertise France, a French public company in charge of international cooperation on large projects.
Past its certification (2017) and once it became operational after receiving its first accreditation to handle BSL-4 risky pathogens (2018), none of the planned 50 French researchers ever showed up at the WIW. The promised Sino-French cooperation project on pathogen studies at the WIV had hit the buffer, even if it would still be occasionally rolled out with some corresponding Chinese demands for supplies of French BSL-4 suits (see [13]).

[10] The ‘maître d’œuvre’ is typically a purely engineering service company that oversees the construction and delivery of the project. In the case of the Wuhan BSL-4, the role ended up being distributed across the French side, the WIV and the Chinese companies involved in the construction. There simply was not such a clear ‘maître d’œuvre’ in charge.

[11] As an example of a well know incident, in 2014 all construction work was stopped for four months after China selected a supplier that did not satisfy the French side. After involvement of the French government, the Chinese side relented and work was able to resume.

[12] One particular incident relates to the decontamination showers being incorrectly cleaned with sodium hypochlorite by WIV personnel in 2016, one year after the end of building construction. This resulted in necessary repairs due to corrosion.

[13] The French intelligence services had early on firmly advised against the export of BSL-4 suits due to the large amount requested while they had become aware of other BSL-4s being constructed (Kunming, Harbin), labs which China had not mentioned during the WIV project negotiations. The clear unwillingness of China to explain what had happened to mobile BSL-3 labs earlier sold by France did not help either.

[14] The Chinese text uses a mix of idioms that can be quite rich in connotations but that are rendered as neutrally as possible; 内外有别: ‘There is an inside and an outside’, 以我为主: ‘We come first’, and finally 实事求是: ‘Seek truth from facts’, a favourite motto of the party since Mao which alludes to adapting foreign imports and influences to Chinese characteristics, a key tenet of ‘socialism with Chinese characteristics’。

[15] France intelligence services eventually became aware of these other BSL-4 labs that were either planned or soon in early phases of construction (such as the shell of the Kunming BSL-4). This created some serious tension as China had told the French side that it had not other BSL-4 lab planned when it signed the MOU.

[16] A rarely discussed apposite may also be found in the case of the BSL-4 of the Taiwan Military Institute of Preventive Medical Research (IPMR), part of the National Defence University. According to unverified Chinese sources, Taiwan purchased the IPMR from France in 1983 under a confidential project with codename ‘White Chicken 16’. A more recent Western source described it as being ‘full of advanced French-made equipment’. It seems that that Taiwan BSL-4 relied on BSL-4 gloved cabinets, one of which would be the unfortunate source of a SARS Lab Acquired Infection in 2003. There is thus little doubt that France played a key role in establishing BSL-4 capabilities in both Taiwan and China.

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Gilles Demaneuf

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