Covid-19 changes the laboratory landscape

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Demand for testing and requirements for remote working tools drive changes in the laboratory

The pandemic has defined the development of laboratory software and technologies, as collaboration and remote working tools become requirements to a productive laboratory.

It has increased demand for laboratory services in areas such as testing, genomics studies and vaccine and drug development. However these demands must be met with restrictions on laboratory space and more demanding project timelines.

To facilitate this research and scale-up testing capabilities, laboratory scientists are using laboratory information management system (LIMS) and electronic laboratory notebook (ELN) software to help manage collaborative work, and promote reduced-capacity working environments in the laboratory.

Patrick Rose, digital science product manager at Thermo Fisher Scientific, notes that there has been a pivot in the tools used in laboratories due to Covid-19. ‘The labs are starting work leaner, they are having to collaborate with other partners, other contract research organisations [CROs] to help battle the pandemic and find the vaccine.

‘What we are seeing is an increased need to work remotely due to alternating days, slimmer shifts trying to minimise the time people are in there together. But, they still need to work on their results, gather and share data and collaborate,’ added Rose. ‘So the tooling and solutions, like the LIMS that we offer, become more pivotal and critical. It is being able to see what other users have done – potentially what they may have done in the last shift, what you need to do for the next shift.’

Tools facilitate remote working

LIMS or ELN systems can help to minimise the time scientists have to spend in the lab, as mobile alerts or other features can help notify scientists when their experiments will be finishing. Streamlining data sharing and access also helps facilitate agile decision making, and lets scientists access data and analyse or work on data from home.

Several LIMS and ELN vendors are now equipping their software with pre-configured workloads to help scientists get set up with key laboratory operations. This reduces the amount of setup and administrative work that needs to be done by scientists, which should lead to increased productivity.

Lauren Taylor, digital science solutions manager at Thermo Fisher Scientific, said: ‘Some of those workflows we have already pre-configured to get customers up and running as quickly as possible. In terms of the integration of instrumentation, for example, you may have specimens in the lab that you want to sequence, that information needs to be put onto the sequencer so that you know which samples you are sequencing, and that information can be relayed back to the correct sample.

‘The integration really is automating the push of information to the sequencers, so that you are not copying and pasting or uploading and downloading files manually.’

Using AI in the fight against Covid-19

AI tools are becoming increasingly useful to laboratory scientists. A partnership announced between Elsevier and ExactCure provides a software platform collaboration to develop and offer to hospitals – without charge – drug-specific exposure models for 20 already approved medicines that are being tested as potential treatments for Covid-19.

Each drug-specific model, generated using ExactCure’s AI-driven simulation platform, will help to predict a drug molecule’s pharmacokinetic properties in each individual patient, according to their age, sex, whether they have other diseases – comorbidities – and other factors, and thereby give guidance to clinicians on likely optimum dosing.

Development of the drug exposure models will leverage data held in thousands of drug-related documents in Elsevier’s PharmaPendium drug data resource, which contains decades of searchable FDA and EMA regulatory approval and related documents on the drugs.

Olivier Barberan, director of translational medical solutions at Elsevier explains: ‘We will provide ExactCure with information held in PharmaPendium that spans more than 50 drug-specific parameters, including PK and pharmacodynamic data, safety data, adverse events and drug-drug interaction records, together with data on drug efficacy. This may encompass many thousands of reports, for example, there were in excess of 13,000 records just for the antiviral drug ritonavir, which is one of the drugs under consideration for Covid-19 therapy.’

ExactCure is exploiting the PharmaPendium data and its own AI tools to build a simulation-based digital companion – a digital twin application for smartphones that patients would use to help make sure that they use medicines safely, and at an appropriate dose and frequency, ‘whether that be an OTC painkiller, or an antiviral medicine,’ Fabien Astic, ExactCure co-founder, said. ‘This can help to prevent underdosing, overdosing, and to prevent drug-drug interactions or adverse events relating to the individual’s health status, or even genetic profile.

‘The AI-based software derives the personalised guidance according to key patient-specific characteristics such as weight, age, gender, renal and liver function, smoking status and genetic background. Importantly, it could also feedback information to the prescribing physician, so that they will know how well the patient is sticking to their drug schedule,’ Astic suggested.

‘Our first model, for paracetamol, could help dramatically reduce overuse of the drug and even prevent overdose-related deaths.’ ‘We signed a partnership with Vidal, a key player of medical information in France, to integrate our technology into their Vidal Sentinel platform designed for hospitals. They call our API [Application Programming Interface] and the pharmacist or doctor can run personalised simulations until they reach what they estimate to be the best posology for a given patient,’ added Astic.

Digital companion apps could also be utilised by the pharma industry to support clinical drug trials and potentially speed time to market, while reducing attrition at the trials stage.

Dosing optimisation for Covid-19

Certara launched the Covid-19 Pharmacology Resource Center in April, an online resource giving scientists around the world access to simulation and modelling tools to aid the design of clinical trials and optimise dosing regimes for candidate drugs such as hydroxychloroquine, and lopinavir/ritonavir, against Sars-CoV-2. Funded by the Bill and Melinda Gates Foundation, and supporting global collaboration in the drive to develop new treatments for Covid-19, the centre offers researchers a workbench of in-silico modelling tools, integrated with existing and emerging data.

The centre offers an accessible outreach of the expertise that Certara provides in the global Covid-19 Therapeutics Accelerator, which has been set up with an initial $125m in funding from the Gates Foundation, Wellcome and Mastercard, through which the World Health Organization, governments, healthcare providers and industry are collaborating to speed the development of therapeutics to treat Covid-19 or prevent Sars-CoV-2 infection.

Craig Rayner, president, integrated drug development at Certara explains: ‘Certara is providing expertise in translational and clinical pharmacology, quantitative science and regulatory strategy to support critical stage decisions, clinical trials design and dosing optimisation for Covid-19.

‘For a virus like Sars-CoV-2, for example, Certara researchers invest significant efforts in bringing the biology and math together to help improve decision making for new therapeutics. One can now evaluate how the virus enters cells, how it interacts and replicates, what the immune system is doing in response, via sophisticated quantitative pharmacology frameworks and predictive tools and then simulate new situations,’ he suggested.

‘We can take huge amounts of data from preclinical models, in vitro testing and clinical experience, as a fundamental foundation on which to use math engines to model what will happen in different trial scenarios, start to simulate clinical trials accurately, and then add data derived from new trials back into the model, and validate in-silico learning,’ said Rayner.

Certara’s Simcyp Simulator has been developed as a suite of modules that simulate drug pharmacokinetics (PK) that can predict and describe how the body affects the drug-drug absorption, distribution, metabolism and excretion (ADME), and how PK may be altered by formulation, patient variables such as age, gender or genotypic information, or concomitantly administered medications.

The Simcyp Simulator links laboratory data to in vivo ADME data and when integrated with and extended to pharmacodynamic (PD) information (how the drug effects the body) such as biomarkers or clinical efficacy and safety, is a powerful tool to support dosing decision-making in new trials.

Keith Nieforth, senior director of Certara’s software division, said: ‘Designing and running clinical trials for any drug or vaccine is hugely expensive and time consuming, so there is a great need to boost efficiency, and improve the likelihood of success.

‘The Certara tools can also model drug activity at particular sites of action, and look at the physicochemical properties of that molecule in the context of other molecules with similar structure and activity, to make predictions on whether the drug will reach target tissues, such as the lung, if we consider Sars-CoV-2,’ Nieforth said.

‘In the case of Covid-19 drug development, the Certara models integrate simulations of drug pharmacokinetics and pharmacodynamics, alongside virus interaction with the host and symptoms.

‘You can then link those models together and that enables you to simulate what you think might happen in clinical trials. Ultimately, modelling and simulation can reduce the number of patients, or trial arms required, as well as evaluate the influence of other design factors on trial outcomes, and so improve the probability of success,’ added Nieforth.

Advancing viral testing

With the world’s focus on the pandemic, LIMS providers are working to develop solutions tailored to assist in the testing and management of virus samples. By streamlining processes, increasing connectivity and reducing manual data entry samples can be tested more efficiently and more accurately.

Edward Krasovec, director of clinical solutions at LabWare explains: ‘Manual data entry can lead to serious errors, meaning that samples cannot be tested or that the specimens cannot be traced back to the correct source. When dealing with healthcare, this means potentially very sick patients missing out on results from their tests.’

John Gabathuler, director of industrial and environmental at LabWare, also highlighted the importance of removing errors from manual data entry processes. ‘They are processes that have not been there previously. They have had to set these processes up, and therefore they are going through them for the first time, or they are not as tried and tested, so the chances of systems not getting the right information can exacerbate problems. With the current situation you want to be as accurate as you possibly can, as fast as you possibly can, because people’s lives depend on it.

‘We are trying to help by putting automated software processes in place to help capture the testing data: that may be challenging because you are out in the field,’ added Gabathuler.

Labware developed the Portable Disease Surveillance Lab kit in partnership with Tangen Biosciences. They recently announced a partnership for LabWare to distribute Tangen’s GeneSpark device as part of the kit in response to the pandemic.

The kit connects to the LabWare LIMS software portal to capture patient demographic and clinical information, document field collection of respiratory swabs for Covid-19 testing, attaining the sample, and rapidly disseminate this data to public health agencies.

Beyond Covid-19, Tangen is making a Flu/Covid-19 Panel that can detect Flu A, Flu B and Covid-19 simultaneously from one patient sample in a single processing run, so that patients with flu-like symptoms will know whether they have flu or Covid-19, or neither.

Richard Birkmeyer, president and CEO at Tangen, said: ‘The pandemic is tragic for many families. Everyone at Tangen Biosciences has been working long hours to have our sensitive Covid-19 assay on the market. More importantly, we believe the combined Covid-19 and Flu A/B test will be a critical surveillance tool for respiratory illness management. In addition to the Covid-19 test, we are also developing a sepsis panel and an antimicrobial-resistant panel, and are currently looking for strategic partners for both.’

The firms are aiming to continue this partnership to include multi-target testing. The combination of Tangen’s rapid, highly sensitive and point-of-care molecular diagnostics and LabWare’s real-time data reporting LIMS software should enable public health systems to react quickly in terms of quarantine guidelines, patient tracing, hotspot monitoring and infection surveillance.

Maintaining interoperability

Covid-19 demands that laboratories adopt new practices and workflows quickly, but when new technologies are created and deployed quickly interoperability can become a challenge. As Labware’s Krasovec points out, the company’s strategy has been to recognise that no single organisation can do it all – collaboration with the right partners is crucial.

With data analytics and AI applications becoming increasingly widespread, new data sources and ways of analysing data are now available. AI and data analytics also asks questions of existing data. Has legacy data been stored in a way that allows it to be easily reused in the future? If that is not the case, then an organisation must clean and order that data before integrating AI into their workflows.

Interoperability between software systems, different workflows and the various outputs that these processes create, are key to providing a stable platform for laboratory data.

As LIMS providers collect and store data for laboratories, it is crucial they play a role in working with specialised software partners to ensure interoperability. ‘It’s not just about having an instrument that can do the test. That is just one part of the process. If you cannot get that test where it needs to go, to the healthcare provider, patient, or public health authorities, then it is a wasted effort,’ noted Krasovec. ‘Not to mention that the people you are testing are out there, potentially not knowing they are infected, and they continue to infect others.

Gabathuler added: ‘That is why we have this enterprise laboratory platform, because there are a lot of parts to it and they can all act up in a nice cohesive joined-up way to help in lots of different areas. You have got a functional platform and then everything can be leveraged from that going forward.’

Rapid adoption of new technologies requires LIMS providers to be agile in ensuring interoperability with software partners. This enables them to provide the infrastructure or platform that can not only interact with instruments and laboratory equipment, but also data analytics or AI software frameworks.

‘There is a rapid adoption of new technologies in the healthcare laboratory in terms of a genetic-based testing platform which has spawned this order of magnitude difference in the amount of data that is created – that data has to be managed,’ said Krasovec. ‘Quite often it involves specialised technologies to interpret that data.’

‘As a LIMS provider, we are not a domain expert in analysing genetic data. It is important we are able to get data that may be captured from an instrument and interact with the software specialised to do that interpretation of these gigabytes of data that can be generated by sequencing processes,’ Krasovec added. ‘That is obviously very important, because no one system is the be all and end all, and they need to coexist and share information with other systems.

‘We manage the workflow process and there may be data analytics that goes along with it that could be done by specialised software. Then we are responsible for distributing the final report to whoever it needs to go to. We have a role in the process. It is important that we are able to interact with the other systems as well,’ said Krasovec.

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