NanoPass is sharing its proprietary MicronJet microneedle device with leading vaccine and immunotherapy companies around the world to assist in development of a Covid-19 vaccine.
The NanoPass device targets immune cells of the skin by harnessing the skin’s potent immune system to improve vaccines and/or to dramatically reduce the dose while achieving the same immunity.
“The human skin is our first layer of defence against many infectious diseases,” says Yotam Levin, MD, CEO of NanoPass. “The skin contains specialized Dendritic Cells that process and induce strong immune responses – that’s why microneedle injections enable reduction of vaccine doses by five-fold, thereby reducing overall cost, required capacity and production time. We believe a reliable injection into the skin is critical for successful activation of broad and effective immune responses, which should be explored for most injectable vaccines.”
The company’s technology is supported by more than 55 completed/ongoing clinical studies with various vaccines and vaccine platforms, including H1N1, H5N1 and live attenuated VZV vaccine, that have shown improved immunogenicity and significant dose-sparing. Pre-clinical evidence with mRNA and DNA vaccines showed promising results.
NanoPass has previously supported US CDC in a Phase 3 infant polio vaccination trial; with ITRC on PPD skin testing; in Type 1 Diabetes immunotherapy; and supported NIAID with devices to evaluate immunogenicity of a pandemic flu vaccine; and multiple vaccine pharma.
NanoPass Technologies flagship product, the 0.6 mm MicronJet, is the first true (<1 mm) microneedle to receive FDA clearance as an intradermal delivery device for substances approved for delivery below the surface of the skin. It is supported by extensive clinical data and regulatory approvals in most major markets including the US, Europe, China and Korea.

Avacta Group, the developer of Affimer biotherapeutics and reagents, has entered into a collaboration with Integumen to evaluate recently generated Affimer reagents that bind the SARS-COV-2 spike protein for the detection of the coronavirus in waste water, to provide a real-time alert system to warn of localised COVID-19 outbreaks.
Over 60 percent of COVID-19 positive patients had gastrointestinal symptoms, such as diarrhoea, nausea and vomiting, and the SARS-COV-2 virus was found in their faecal samples. Sampling waste water from households may therefore provide an early warning system for localised outbreaks in communities.
Recently, Avacta announced that it had generated a number of highly specific Affimer reagents that detect the SARS-COV-2 virus spike protein for use in diagnostic tests and in neutralising therapies.
The collaboration with Integumen, announced 13 July, aims to evaluate some of these Affimer reagents in next-generation sensors, based on the real-time bacteria detection and alert system1 developed by Rinocloud, a subsidiary of Integumen, with the aim of integrating these sensors into Modern Water’s Microtox water contamination system to detect the coronavirus. The award-winning Microtox system, which can detect the presence of contaminating bacteria, virus and toxins, is distributed by Modern Water and has a global footprint of over 3,000 installations. The proposed Affimer sensors would be consumable items to be replaced on a roughly monthly basis.
Once initial testing of the Affimer reagents is completed over the next few weeks, validation of the sensors will be carried out using SARS-COV-2 virus samples in a containment level 3 laboratory at the University of Aberdeen. Upon successful completion of this evaluation, Integumen and Avacta will enter into a supply agreement to allow Integumen to manufacture and commercialise the waste water detection sensors globally by retrofitting into Microtox systems.

The new coronavirus, SARS-CoV-2, causing a disease that has been called COVID-19, was first identified in Wuhan, China in December 2019, and has been transmitted widely across the globe. This article gives a general overview of what is currently known in a fast developing situation.

The advent of molecular biology techniques has revolutionized disease diagnosis. CLI discussed with Dr Chandrasekhar Nair from Molbio Diagnostics the benefit that these techniques have brought and how these technologies are being adapted for point-of-care use for rapid diagnosis and the benefit of rural populations.

What has the impact of molecular biology been on disease diagnosis and treatment?

Accurate and timely diagnosis of infectious diseases is essential for proper medical management of patients. Early detection of the causative agent also enables care providers to intervene in a precise rather than presumptive manner and institute adequate measures to interrupt transmission to the susceptible population in the hospital or community.
The conventional diagnostic model for clinical microbiology has been labour and infrastructure intensive and frequently requires days to weeks before test results are available. Moreover, due to the complexity and length of such testing, this service was usually directed at the hospitalized patient population. Bacterial/viral culture has been – and continues to be – the gold standard for detection. However, time taken for some pathogens to grow, coupled with the difficulty in culturing some pathogens has resulted in a demand for alterna tive techniques that would allow direct pathogen detection in clinical samples rapidly.
The application of engineering techniques to the technological revolution in molecular biology has greatly improved the diagnostic capabilities of modern clinical microbiology laboratories. In particular, rapid techniques for nucleic acid amplification and characterization combined with automation and user-friendly software have significantly broadened the diagnostic arsenal. Among the molecular techniques, applicability of PCR-based methods has gained popularity as it allows for rapid detection of unculturable or fastidious microorganisms directly from clinical samples.
Clinical laboratories are increasingly finding utility of molecular techniques in diagnosis and monitoring of disease conditions. Nucleic acid amplification tests are becoming very popular in the diagnosis and management of viral infections [hepatitis B and V viruses (HBV, HCV), human immunodeficiency virus (HIV), influenza virus, etc] because they allow determination of the viral load. In most cases, they are now considered a reference, or gold standard method for diagnostic practices such as screening donated blood for transfusion-transmitted viruses [cytomegalovirus (CMV), HIV, HCV, etc]. Another important case is the use of molecular tests for the detection of the tuberculosis (TB)-causing bacterium Mycobacterium tuberculosis (MTB). Considering the limited sensitivity of smear microscopy, coupled with the steady rise in drug-resistant MTB, rapid molecular tests appear promising.

What are the challenges of implementing molecular diagnostic techniques in developing countries?

For a long time the field of molecular diagnostics has been limited to the domain of large centralized laboratories because of its dependency on complex and expensive infrastructure, highly skilled manpower and special storage conditions. This investment has also resulted in the need for batch testing to make such facilities affordable. As a result, patients and samples need to travel long distances for a test to be conducted and results are delayed, resulting in a loss of follow-up. These factors have led to a concentration of such facilities in urban centres, and poor reach of molecular diagnostics techniques, particularly in low and middle income countries (LMICs). The poor testing rates in the current COVID-19 pandemic are evidence of such dependence on centralized facilities, limiting the ability to test on demand and take appropriate action.
The lack of timely access to good diagnostics resulting in either delayed or inaccurate diagnosis by other methods has been increasingly resulting in spread of disease and poor treatment outcomes.

How can these challenges be overcome?

We need to increase the reach of molecular diagnostics techniques. Given the economic constraints in LMICs, point-of-care technology (POCT) hold a lot of promise and several major global initiatives are devoted to providing such devices. Facilities for testing that can be deployed, set up and run quickly, at affordable costs, with minimal infrastructure requirements and training are critical to the success of the efforts to increase reach. Mobile data coverage, that exists with reasonable density in LMICs, could also be leveraged for better programme management and hotspot detection.
The success of these technologies also depend on uncompromised performance and adherence to quality standards.
Furthermore, designers of POCT devices need to focus on key user requirements which include: (1) simplicity of use; (2) robustness of reagents and consumables; (3) operator safety; and (4) easy maintainability.

What is Molbio Diagnostics doing to meet these demands?

The Truelab® Real Time Quantitative micro PCR System from Molbio Diagnostics brings PCR technology right to the point of care, at all laboratory and non-laboratory settings, primary centres, in the field, near patient – essentially at all levels of healthcare, thereby decentralizing and democratizing access to molecular diagnostics. With a large and growing menu of assays for infectious diseases, this rapid, portable technology enables early and accurate diagnosis and initiation of correct treatment right at the first point of contact. The platform is infrastructure independent and provides complete end-to-end solution for disease diagnosis. With proven ability to work even at primary health centres and with wireless data transfer capability, this game changing technology brings in a paradigm shift to the global fight in control and management of devastating infectious diseases.
Under the aegis of the Council of Scientific and Industrial Research and New Millennium Indian Technology Leadership Initiative partnership, Bigtec Labs (research and development wing of Molbio Diagnostics Pvt. Ltd.) has developed a portable and battery-operated micro PCR system that has since been extensively validated [under the Department of Biotechnology and Indian Council of Medical Research (DBT & ICMR)]. Bigtec has also developed various tests and nucleic acid preparation devices to facilitate ‘sample to result’ molecular diagnostics in resource limited settings. The micro PCR system has since been launched in India through the parent company, Molbio Diagnostics, which has its manufacturing and marketing base in Goa, India.
The system works on disease specific Truenat™ microchips for conducting a real-time PCR. The sample preparation (extraction and purification) is done on a fully automated, cartridge-based Trueprep® AUTO sample prep device. The purified nucleic acids are further amplified on the Truelab® Real Time Quantitative micro PCR System which enables molecular diagnostics for infectious diseases at the point of care.
This compact battery-operated system has single testing capability and provides sample to result within 1 hour. Hence, it enables same-day reporting and initiation of evidence-based treatment for the patient.It also has real-time data transfer capability (through SMS/email) for immediate reporting of results in emergency cases. Physicians benefit from this technology by having a definitive diagnosis, early in the infection cycle, without patients/samples having to travel extensively to centralized facilities.
The Truelab® Real Time Quantitative micro PCR System from Molbio Diagnostics is a cost-effective and sensitive device that can detect diseases accurately with high specificity. The device is battery-operated and portable. This offers the additional advantage of placing the device in almost any kind of laboratory setting, unlike other devices that require uninterrupted power supply, elaborate infrastructure and air-conditioning.
Considering our platform’s potential to perform molecular diagnostics for infectious diseases at the point of care, India has initiated screening for COVID-19 using the Truenat™ Beta CoV test available on the Truelab® Real Time Quantitative micro PCR System. This will allow same-day testing, reporting, and initiation of patient isolation, if required – thereby reducing the risk of infection spreading while waiting for results.
The successful translation of our innovative concept into a product was made possible by Molbio’s multi-disciplinary workforce – with a constant mission to enable better medicine through precise, faster, cost-effective diagnosis at the point of care; to provide every patient access to the best healthcare through cutting edge technologies. Molbio aims to be a leading global player in the point-of-care diagnostics arena by continuing to innovate and bring new technologies for social betterment.

The company is based in India – how does this affect what you do, how is the clinical lab diagnostics industry developing in India and does it create more chances for you?

In India, we have over between 45¦000–50¦000 in vitro diagnostic laboratories – every one of which uses routine conventional diagnostic methods. Only a handful of them have adopted molecular diagnostic testing for reasons mentioned above. But this is changing with the advent of Molbio’s Truelab® platform, with regular standalone laboratories that were, up to now, outsourcing molecular testing, starting to perform the tests themselves. In the short span of a few years, Molbio has established itself as a company focused on making a significant impact in aiding infectious disease diagnostics worldwide with our extensive testing menu.
Our test range covers infectious diseases such as TB, the entire hepatitis range, High risk HPV, H1N1, along with the recent addition of tests for COVID-19, catering to a large population base and addressing diseases with a very significant global mortality percentages. Our rapid test development for Nipah virus and the leptospirosis-causing Leptospira bacteria show our commitment to neglected tropical diseases. Going forward, Molbio will continue to increase the assay range looking at the needs of the global LMIC geography.
The Truenat™ MTB and MTB-RIF tests have started playing a significant role in India’s mission to becoming TB-free by 2025. We would be happy to partner with other National TB Programmes in achieving sustainable development goals well before 2030.
Our vision has always been ‘innovate to have a real impact’ and hence Molbio will continue to bring in newer POCT platforms so that the benefits of science and technology reach the masses.
The interviewee
Dr Chandrasekhar Nair, BE, PhD, chief technical officer, Molbio Diagnostics

For further information visit Molbio Diagnostics (http://www.molbiodiagnostics.com)

Expert opinions from Dr Heidi Mendoza
There are many assessments to make when adding a new test to a lab’s collection. Dr Heidi Mendoza, acting consultant clinical biochemist at Raigmore Hospital, Inverness, UK, shares her experiences and observations of doing exactly that in both ordinary circumstances and during a pandemic, as well as having to contend with the geographic challenges imposed by the nature of life in the Scottish Highlands.
Can you provide a little background about yourself and where you work, please?
I am a clinical biochemist based in Raigmore Hospital, which is a small hospital in the Scottish Highlands. In my current role I provide clinical advice and interpretation for biochemistry tests for general practitioner (GP) practices and three hospitals across the Highlands. Working in the Highlands is incredibly rewarding, but also very challenging! It can take between 2 and 6|hours to travel between hospitals and our patients may have to travel by plane or boat to be seen, with journey times of +12|hours depending on where they live. It really puts the laboratories under pressure to get it right for the patient. Repeat testing isn’t as simple or straightforward as it would be in a city and we have to have excellent systems in place for reporting critical results and getting patients into hospital or transferring them between hospitals. Getting the right test, in the right place, with the right turnaround time is really important for our patients and for our clinicians.
What are the usual circumstances in which you would think about bringing a new test into the lab’s repertoire?
Any new test is a cost pressure on our National Health Service (NHS) and can only be brought in when it demonstrates clear benefits for patients. We have brought in two new tests in the last 12|months that are good examples of the different ways we can bring in new tests to our laboratory.
The first test is the NT-proB-type natriuretic peptide (NTproBNP) test. NTproBNP is used to investigate patients with suspected heart failure and the results can be used to determine whether a patient needs an echocardiogram (ECHO) or not. If they do need an ECHO the NTproBNP result can be used to split patients into those who need urgent ECHO (2|weeks) or routine ECHO (6|weeks). In theory this is a perfect test to implement as it will benefit patients and is cost-effective with respect to the more expensive ECHO investigation. However, NTproBNP has been implemented in other hospitals without reducing ECHO waiting times or the number of ECHOs performed! To ensure that this didn’t happen in our service, I spent 6|months before implementation of the test liaising with cardiologists and GP representatives from across the Highland region. We changed the ECHO referral pathway to include NTproBNP and created useful guidance for GPs on when to, and importantly when not to, request NTproBNP. We implemented the test just under 1|year ago and have seen a positive effect on ECHO referrals. We will still have to attend a 1|year post-implementation review with the Hospital Board to present our audit data and show that investment in the service by introducing a new test has benefited patients and other areas of the service.
Procalcitonin is the second example. Procalcitonin is a test that can be used in the investigation of sepsis and guide the use of antibiotics. Procalcitonin was not a test available in our hospital before the COVID-19 pandemic. Procalcitonin is not increased in the majority of adult patients with COVID-19; however, an elevated procalcitonin may suggest superimposed bacterial infection and be used to guide treatment of these patients and improve patient outcomes. Early in the COVID-19 pandemic we were approached by our Intensive Care Unit (ITU) and Microbiology consultants who requested that procalcitonin be available for our COVID-19 patients in ITU to guide their antibiotic treatment. We implemented procalcitonin in less than 4|weeks with help from our instrument manufacturer, external quality assessment providers and other Scottish hospitals who provided anonymized patient serum with known values so that we could verify our assay as quickly as possible. We are now in the process of putting together a business case and following the evidence base which will determine whether we continue to offer the procalcitonin test.
How would you usually go about adopting a new test?
As highlighted in the two examples above, we must agree a clinical need for a test and then liaise with the users of the service to find out how the test should be implemented into the patient-care pathway. Once we have worked out the clinical utility of the test, then we can carry out the laboratory verification of the test and the laboratory workflow. Verification is very straightforward. For example, the between-batch and within-batch precision, accuracy, linearity on dilution, interferences and sample stability for a test need to be evaluated. The implementation of the test then must be followed by an audit which shows that the test is being used as intended and giving the benefits predicted. If not, the test may need to be withdrawn. The hardest part of the entire process is agreeing how a test is going to be used and fitting it in to the patient-care pathway.
In the situation of the COVID-19 pandemic, we have a new disease, caused by a new virus, and new tests that have been created very quickly. How do you start to use a new test in these circumstances – are there any differences in procedure?
There is no difference in the steps that need to be performed we just need to be able to do everything in a much shorter time frame. That is actually much easier than it sounds. In the NHS, the laboratories from different parts of the country are great about helping other laboratories. We regularly share protocols, data and learning. If a new test is released we’ll contact another laboratory and they’ll share their local experience and any problems they have had with the test.
For procalcitonin implementation I contacted the laboratory in Dundee, UK, and they helped us out by lending us kits and reagents, sending us anonymized patient serum with known procalcitonin values, and sharing their data and verification protocols. This allowed us to complete verification incredibly quickly. We will still have to gather the data and evaluate whether the test is providing the benefit that we predicted when we established the clinical need.
What are the challenges regarding validation, reference levels, results interpretation and reporting?
Verifying tests is straightforward as we are always evaluating tests in clinical laboratories so are very experienced. Results interpretation can be quite difficult. If we need clinicians to change patient management based on a result then we have to provide them with very clear local guidance on what we want them to do with a result. This might be different from the action they would take in another hospital with different patient pathways, different pressures on patient turnaround times, and different diagnostic facilities. This is where good working relationships with users of the service are key to test implementation. If you just implement a new test without working out where it fits in the patient pathway, it doesn’t matter how great the test is, as it is unlikely to be used well and may not improve patient care.
What do you have to think about in terms of logistics?
Many laboratories are understaffed due to a combination of unfilled vacancies and staff on long-term absence. The additional work involved in verifying and implementing a new test does put pressure on staff. However, NHS laboratory staff are highly trained and dedicated. When the staff know how a test is going to be used and the benefit to the local community, they support the implementation and the extra work involved.
Biocontainment and staff safety have been important considerations during the COVID-19 pandemic. We had to adhere to government guidance in the transport, analysis and disposal of samples from patients with suspected COVID-19. This changed laboratory workflows and slowed us down, creating longer turnaround times.
Logistics are a serious consideration for us owing to our geography. Reagent shortages or delays in deliveries have a big impact on small laboratories as they can’t store much surplus reagent stocks because of expiry dates. Unexpected overuse or underuse of a new test can be quite challenging and leave the laboratory short of tests or with expired, wasted kits. There are also several times during the year when the roads are impassable between our central and rural laboratories. We have been down to single numbers of tests remaining several times over the last few years or had failed delivery from manufacturers in winter. There was also a shortage of procalcitonin reagent as there was such a surge in the use of the test during the COVID-19 pandemic. Again, working closely with users of our laboratory services has enabled us to rationalize the use of the test until the global shortage of reagent ended. On a number of occasions we have also shared reagents with other Scottish laboratories to ensure that none of the laboratories were left without reagents.
What has been learnt from the current coronavirus situation about diagnostic testing during a pandemic that would help to improve the process in future?
The coronavirus pandemic has shown how robust the infrastructure of the NHS is in Scotland and how adaptable laboratories can be when required. The laboratories really pulled together and worked towards a common goal delivering testing to COVID patients and non-COVID patients during a crisis. The two things that made this possible were: (1) Having a very clear goal – delivery of a service with new testing during a pandemic; and (2) Finances changes which needed to be made to deliver the service got rapid financial approval. How do we take these lessons learned and apply it to the routine delivery of laboratory services? Finance will always be a limiting factor – as it should be! Healthcare is expensive and it is up to us as healthcare professionals to deliver a cost-effective and affordable service. In contrast, having a clear goal, is definitely something that we could do better in the future. In the case of the pandemic, laboratories found different solutions based on local geography, resources and incidence of COVID. The changes made by laboratories in the remote Highlands and Islands were similar, but different than those made by laboratories in major cities. The staff that delivered the service found the best solutions to the goals set by the government – that is the real lesson we need to take away. We need to give very clear goals to services and let local expertise and knowledge drive the changes to solve the problem.
The expert
Heidi Mendoza BSc MSc PhD RCPath
Blood Sciences Department, Raigmore Hospital, Inverness IV2 3UJ, UK
E-mail: heidi.mendoza@nhs.net