Francis Crick Institute
Reliable testing is essential to trace and contain the spread of COVID-19 and to allow healthcare workers to safely deliver care. Working with local partners, the Francis Crick Institute has repurposed its laboratories, using in-house equipment and skills, and opened a drive-through testing service, to support the NHS with diagnostic testing. The Crick’s head of biological safety, Dr Timothy Budd CMIOSH, tells us more.
Q. How did you approach the switch from a research lab to a testing facility?
In March, when it became clear that the country was going into lock down, many senior scientists at the Crick Institute, including Charles Swanton, recognised that a lack of rapid testing would be a major hinderance to the ability to control viral spread. Using his links with University College London Hospitals, Charles set up a working group to convert laboratories here into a rapid real-time polymerase chain reaction (RT-PCR) screening facility for healthcare workers and patients.
Five large laboratories at the Crick and the supporting infrastructure were repurposed, including the biosafety level 3 facilities and their extensively trained staff. The testing facility that the Crick provides is now able to achieve a turnaround time from sample to result of around 24 hours. Ten to fifteen RT-PCR machines (all of the same make) are utilised to extract RNA from viral samples using our own in-house extraction kit reagents (made to circumvent potentially limited supplies of the commercial kits normally used to extract viral RNA).
From the start, the Crick engaged with its scientists, bringing together groups of the most experienced individuals to develop the processes. This was especially important around the most hazardous part of viral inactivation to ensure those undertaking this part of the work were comfortable with the environment and work they were doing. This early intervention ensured the process was correct, from development of the Standard Operating Procedures (SOPs) to the multiple dry runs conducted with the trained users.
The Crick’s sample testing pipeline was set up in around a three-week period. From this point on, the team was expanded by training additional biosafety level 3 competent staff. However, the whole process is more than the just the biosafety level 3 group and it has only been a success because of the hard work and dedication of all the other researchers, admin and support staff involved in the process, from sample receipt to result publication.
Q. What precautions are in place to deal with swab samples that are potentially infected?
The Crick mostly receives oral and nasal swabs (that can either be wet or dry) and they are all treated with the presumption of them being positive for coronavirus. Sample tubes arrive packed in zip lock bags (usually double bagged) and are visually inspected without removing them from their bags by staff wearing lab coats and disposable gloves. Any individual samples that have integrity issues (for example are damaged or leaking) are put aside for further inspection and recovery in a microbiological safety cabinet within the biosafety level 3 facility. All surfaces and transport boxes are sprayed with an appropriate disinfectant. All waste and lab coats are autoclaved on site before respectively being sent for disposal and laundry off site. This initial stage allows the samples to be identified and barcoded so that the results ultimately get back to the right individuals.
Once the samples are barcoded, they are taken into biosafety level 3 microbiological safety cabinets where the samples are removed from their packaging and inactivated. The inactivated sample vials go through a further process of disinfection so that they are safe to remove from the cabinets and subsequently from the biosafety level 3 facility. They are then taken to complete the PCR analysis to detect whether SARS-COV-2 viral RNA is present or not.
Q. How did you approach the risk assessments and standard operating procedures suitable for the pathogen?
Normally the risk assessments and standard operating procedures for genetically modified and wild-type high hazard pathogens are written by the Crick’s scientists and then reviewed and approved by our biosafety practitioners, including myself. However, in this instance these documents were written primarily by myself using information from PHE, Health Services Laboratories (who ultimately accredited all our procedures), the government’s COVID webpages as well as information from our own scientists wishing to do SARS-COV-2 research.
The Crick has biosafety level 3 expertise and facilities on site. The need to get an accredited testing facility running in the shortest possible time, coupled with the fact that we were dealing with a pathogen whose transmission and pathology was (and still is) not fully understood, was a significant influence on our decision to utilise these facilities rather than our level 2 biosafety spaces.
Having higher containment laboratories on site also means that we are highly regulated by the HSE who routinely conduct scheduled intervention visits to site several times a year. As such, we are well practiced in taking into account human factors and task analysis to creating these types of risk assessments and related standard operating procedures.
Personally, having a biological science background, a PhD and a 20-year career in biomedical research safety, plus the experience of regularly working with inspectors from the HSE’s microbiology and biotechnology unit obviously helped me in this process. No testing was started at the Crick until the HSE had been notified and we had received permission back from them.
I also took the time so as not to rush the process as the intention was for it to be correct from the start so that it only needed fine tuning as we learnt from the initial rollout of the protocols. The use of clear, concise language was important for many reasons. Firstly, it helps to minimise the chance of accidental exposure as well as to prevent spoiled samples and results. Perhaps more importantly, it is important to recognise the global nature of the Crick’s efforts in confronting this global pandemic. More than 50% of the Crick’s staff originate from abroad. The time and effort put into making sure that the SOPs were easily readable and understood by staff for whom English is a second language should be obvious.
Q. How did you take into consideration human factors such as fatigue?
Fatigue was a major factor in the planning. There was an imperative to avoid contamination occurring between samples and to avoid mixing samples, both of which could result in individuals receiving an incorrect diagnosis. We calculated that we would have the capacity to process around 3000 samples per day. My colleague Tammy Krylova developed a working schedule for those working on sample inactivation at the biosafety level 3 stage which provided a maximum session time of one hour. Each session was to be followed by a prolonged break to allow for a maximum of four sessions per day per person. Obviously, such working practices help to ensure sample integrity and serve to minimise the risk of exposure.
Q. How did you train more than 40 people – while adhering to social distancing – so quickly?
The new biosafety 3 coronavirus procedures were based on the control measures utilised by Mycobacterium tuberculosis bacteria research groups as this is another highly contagious airborne respiratory pathogen. The major challenge was getting everyone else up to the same high standard that the Mycobacterium tuberculosis researchers employ. Other biosafety 3 researchers working on non-respiratory pathogens such as malaria and HIV were the first to be trained up and then biosafety 2 researchers were also trained to reach a suitable number of people to undertake the work.
The challenge was to attain a uniform level of competency across all of these people. I believe we have now reached this level as the existing biosafety 3 workers are comfortable working alongside the newer trained staff and the error/spoilage rate is currently essentially zero.
Q. How did you keep the usual OSH plates spinning?
Lockdown has proved a slight blessing in this respect as we currently have around 250 people on a site that was designed for more than 1600 staff. A good percentage of the safety team and our in-house emergency response team are on site everyday as a lot of them are engaged in supporting the testing and other essential work at the Crick. Also, being a modern building, there are extensive automated fire detection and fire suppression systems incorporated into the building. A lot of these respective teams are also first aiders, so we are fortunately well covered. Lone working is not an issue as we have an automated tagging system.
Q. How have you approached the responsibility of protecting workers travelling to work to carry out these frontline roles?
A lot of people required to come into work live near enough to walk or cycle and, because they have been classified as essential workers, some have chosen to drive after getting parking permits from the local council. In-house sanitiser stations have been installed at entrances and other communal areas. Additional cleaners have been employed to regularly clean commonly touched surfaces such as door handles. Furniture has been rearranged in the welfare and rest areas to promote social distancing, and we have introduced staggered lunchtimes. There are now lots of two-metre distance markings throughout the workplace.
Q. How many tests did you begin processing each day and what are the numbers now?
The numbers were low at the start which helped the Crick to embed the processes in the first place. We know we can comfortably do a thousand samples in a day and are confident that we can expand this to 3000 per day. This is down in part to effective planning, but also reflects the drive, determination and enthusiasm of everyone in the project. It has been my privilege to work with these people.
