Leading Edge 2021 Issue 1

2021 Issue 1 Alpha Laboratories Ltd. Diagnostics IN THIS ISSUE ... Faecal Pancreatic Elastase - Case Study BÜHLMANN fPELA® turbo on cobas® c501 6-7 Invasive Aspergillosis Screening in Critical Care Patients 2-3 Why Wait for Results? The Benefits of Rapid and Point-ofCare Monitoring of Therapeutic Drugs 8-9 Efficient, Convenient and Hygienic Extraction of Stool Samples with BÜHLMANN CALEX® Cap 4 IBDoc® Home Calprotectin Test - Correlation with Laboratory Results - Case Studies 10 Sharing the Load of Faecal Calprotectin Sample Extraction Case Study- County Durham and Darlington NHSFT 5 The History of IVD ELISA Test Development for Peripheral Neuropathies by BÜHLMANN 11 Extended Sample Stability with CALEX® Cap 5 New ShuttlePouch™ Convenient and Cost-Effective Sample Vial Transport Pouch 12 Detecting COVID-19 Associated Pulmonary Aspergillosis

2021 ISSUE 1 2 Aspergillosis is an opportunistic fungal infection caused by species of the Aspergillus genus. These are ubiquitous environmental filamentous fungi commonly found in soil, rotting leaves and compost, dust, crops and plants, damp buildings, and air conditioning units. Aspergillosis is contracted by inhalation of the spores of the Aspergillus fungus into the lungs. However, as an opportunistic pathogen, the spores very rarely cause disease in healthy individuals with fully functioning immune systems. Unfortunately, in the medically vulnerable, particularly those with compromised immune systems, these same spores can multiply, forming fibrous fungal growths in the lungs and can ultimately lead to a serious, often fatal fungal infection called invasive aspergillosis. Some may have no symptoms but others can suffer haemoptysis (coughing up blood), fever, chest pains and difficulty breathing. Some immunocompromisations or vulnerabilities, may be due to underlying conditions, such as diabetes or other autoimmune disorders. However, some can be caused by co-infection with another pathogen, particularly respiratory pathogens such as the influenza virus. This vulnerability to opportunistic pathogens is a particular problem for patients receiving invasive mechanical ventilation. Many studies have shown that ventilation increases the risk of fungal infection and that this risk increases with ventilation duration. Aspergillosis and COVID-19 With the emergence of COVID-19 there has been a marked increase in patients admitted into intensive care units (ICU) and particularly those requiring invasive ventilation. With this comes the inevitable increased risk of opportunistic fungal infections. Evidence has shown that infection with Coronavirus-Associated Pulmonary Aspergillosis (CAPA) greatly increases patient mortality risk. Bartoletti et al.1, published in July 2020 found a high prevalence of CAPA in severely ill COVID-19 patients and an elevated 30-day mortality rate (44%) in these patients, when compared to non-aspergillosis patients (19%). This suggests that the presence of invasive aspergillosis worsens prognoses for COVID patients. While COVID-19 treatment has improved, treatment for aspergillosis is much better researched and as such may improve prognoses and survival rates of COVID-19 patients. A review by Koehler et al. concluded: “Clinicians caring for patients with ARDS due to COVID-19 should consider invasive pulmonary Aspergillosis and subject respiratory samples to comprehensive analysis to detect co-infection2.” New Guidance New guidance has been provided by the European Confederation of Medical Microbiology (ECMM) for the diagnosis and management of patients with acute respiratory distress syndrome (ARDS) and/or ICU treatment under mechanical ventilation due to suspected pneumonia. References 1.Bartoletti, M et al (2020) Epidemiology of Invasive Pulmonary Aspergillosis Among Intubated Patients With COVID-19: A Prospective Study. Clinical Infectious Diseases 2020 Jul 28 2.Koehler, P et al. (2020), COVID-19 associated pulmonary aspergillosis. Mycoses. 2020;63:528–534 Invasive Aspergillosis Screening in Critical Care Patients In accordance with guidance from the European Confederation of Medical Microbiology (ECMM) Now is the time for in vitro diagnostics! The Coronavirus pandemic is offering an unprecedented opportunity to demonstrate the true benefit of diagnostics in the modern world. Never before has there been so much public awareness of the role of clinical scientists and diagnostic processes. However, the British In Vitro Diagnostics Association (BIVDA) highlight the fact that although 70% of clinical decisions are aided by a diagnostic test, only 1% of the budget is spent on IVDs. The last year has seen multiple demands on the diagnostics sector. We commend those scientists who have risen to these challenges to rapidly introduce new testing kits, sample collection and transport methods and the capacity to meet the requirements for the daily turnaround of vast numbers of COVID-19 tests. Whilst the routine testing and screening in other areas was reduced in the early part of the pandemic, it is now encouraging to see these returning. Particularly, in areas such as Bowel Cancer Screening. Adaptability has certainly been a key word of the last 12 months. Finding different ways to monitor ongoing conditions whilst minimising patient contact is particularly pertinent for vulnerable patients. The IBDoc calprotectin home test is one solution which has been introduced recently by numerous trusts to support their IBD patients. You can read about verification of the home test results compared to laboratory data at two sites on page 10. We hope you find this and the other articles in this issue of interest and that we can help in the continuation of your critical work. Wishing good health for you, your families, friends and colleagues.

www.alphalabs.co.uk 3 sõna Aspergillus Galactomannan Lateral Flow Assay (IMMY Aspergillus GM LFA) The guidance from the ECMM specifically recommends the use of IMMY’s Aspergillus GM LFA both as part of the initial microbiological diagnostic pathway in all ICU or ARDS ventilation patients and also as part of a continual, tri-weekly screening program for SARS-CoV-2 and Influenza A/B positive patients. Aspergillus GM LFA is an immunochromatographic test system for the qualitative detection of Aspergillus Galactomannan in serum and bronchoalveolar lavage (BAL) samples, providing a simple, rapid diagnosis of invasive aspergillosis. The Aspergillus GM LFA is a test which works in synergy with other procedures such as microbiological culture, biopsy histological examination and radiographic evidence, combining to aid in the diagnosis of aspergillosis. Providing exceptional ease-of-use along with high sensitivity, specificity and rapid 30-minute test time it eliminates the need for batch testing and gives results in just 45 minutes. The sõna LFA Cube Reader simplifies the assessment of the intensity of the appearing lines. This bench top analyser is intended to be used as an aid in the interpretation of results of the Aspergillus GM LFA. For more information on the sõna Aspergillus Galactomannan Lateral Flow Assay (Asp GM LFA) immunochromatographic test system, please visit: www.alphalabs.co.uk/af2003 Virology Bronchoalveolar Lavage (BAL) Microbiology Tracheal and bronchial inspection or tracheal aspirate Respiratory viruses including SARS-CoV-2 & Influenza A/B Direct microscopy culture Susceptibility Bacterial & fungal specific PCR Galactomannan (GM) from BAL/TA fluid If available: IMMY™ Aspergillus lateral flow assay (LFA) Microbiology Serum GM IMMY™ Aspergillus LFA and ß-D-glucan screening (if available) Tracheal and Bronchial Inspection (consider risk of aerosolization of SARS-CoV-2) Direct microscopy High volume culture Susceptibility testing of min 5 isolates or screening agar with azoles Specific fungal PCR (Aspergillus spp.) GM from BAL/TA fluid One of the following signs or symptoms triggers repeat chest CT after 7 days ■ Infiltrates or specific invasive Aspergillosis (IA) signs on prior chest CT ■ Microbiological findings indicative of IA ■ Refractory fever ≥3 days of appropriate antibiotic therapy ■ New fever after a period of defervescence of ≥48 hours while still on antibiotics without other cause ■ Haemoptysis ■ Pleural friction rub or chest pain ■ Worsening respiratory insufficiency despite appropriate antibiotic therapy and ventilator support Day 0-0+2 Day 0 If SARS-CoV-2 or Influenza A/B positive 3 x a week until discharge from ICU or defervescence for ≥7 days with improved lung function Day 7±3 Without Improvement

4 LEADING EDGE - 2021-1 Weighing the sample is still considered the Gold-Standard sample extraction method for calprotectin. However, this is a time consuming and inconvenient method. Providing very high correlation to the weighing extraction method, the BÜHLMANN CALEX® Cap is a stool extraction device containing a measured amount of extraction buffer. The features of the CALEX device are unique, providing a safe and efficient extraction process. It improves laboratory workflow and efficiency by eliminating the need for sample weighing, pipetting or decanting. CALEX is fully compatible with automated procedures such as the BÜHLMANN fCAL® turbo random access immunoturbidimetric calprotectin assay. Application as a primary tube for DS2 ELISA robots and many clinical chemistry analysers enables direct loading of the extraction device onto sample processors. It is for exclusive use with all BÜHLMANN calprotectin assays and the fPELA Assay for Faecal Pancreatic Elastase. CALEX offers ease of use for laboratory personnel and patients, providing an optimised sample dilution for maximum efficiency in stool extraction. The extract stability of 7 days at room temperature allows batching to suit the laboratory routine. Fit for Purpose? In a recent letter to the Annals of Clinical Biochemistry1 a team of scientists from Black Country Pathology Services and the Royal Wolverhampton NHS Hospitals Trust, reported on their evaluation of calprotectin results measured from CALEX Cap extracts compared to the manual weighing extraction method. The team compared 56 homogenized stool samples and 11 external quality assurance (EQA) samples. Interbatch imprecision and stability of extracts were also evaluated. Extracts were analysed for calprotectin using BÜHLMANN fCAL turbo reagent on an Abbott ARCHITECT c16000. Data is presented in Figure 1. The team concluded that “Considering the non-homogenous nature of stool samples, Calex devices demonstrate similar accuracy and imprecision to the gold standard manual method for extracting faecal calprotectin. Our results differ from those previously reported2 but may be explained by the fact that all assays in this report were performed by a single operative. Compared with the manual method, the Calex was easy to use, reduced staff time, used fewer consumables (such as inoculation loops and centrifugation tubes) and improved health and safety by avoiding further direct contact with the specimen after initial sampling. Calex devices are fit for purpose, easy to use and offer a quicker extraction process compared with manual weighing and will therefore enable increasing demands of a faecal calprotectin service.” References 1. Kaur S, et al. Annals of Clinical Biochemistry 2020, Vol. 57(4) 332–333 journals.sagepub.com/home/acb 2. Juricic G, Brencic T, Tesija-Kuna A, et al. Faecal calprotectin determination: impact of pre-analytical sample treatment and stool consistency on within- and between-method variability. Biochem Med (Zagreb) 2019; 29: 010707. Efficient, Convenient and Hygienic Extraction of Stool Samples with BÜHLMANN CALEX® Cap Figure 1 Comparison of manual weighing to commercial CALEX devices for the measurement of calprotectin following extraction from stool samples. (a) Passing-Bablok linear regression analysis and (b) Bland-Altman difference plot.1

www.alphalabs.co.uk 5 Sharing the Load of Faecal Calprotectin Sample Extraction by Laura Bernstone, Principal Clinical Scientist, Clinical Biochemistry at County Durham and Darlington NHS Foundation Trust Clinical Biochemistry at County Durham and Darlington NHS Foundation Trust is based on two main sites. We have busy 24/7 laboratories at both Darlington Memorial Hospital and University Hospital of North Durham, which are located around 25 miles apart. Faecal Calprotectin Workload We have a significant faecal calprotectin workload, receiving up to 650 samples each month. GP patients account for the biggest proportion of these although we also receive a significant number from patients under the care of the Gastroenterology team, usually for monitoring patients with known inflammatory bowel disease. We are able to provide a turnaround time of 7 days from when the sample is received in the lab to the final reporting of the result. We implemented the BÜHLMANN fCAL® turbo assay in 2018, which allowed us to run samples on our mainline Siemens ADVIA® XPT analyser in the Darlington laboratory. Although the test is only run on one site, faecal calprotectin samples arrive from GP and hospital patients at both the Darlington and Durham sites and it was decided to perform the extraction process on both sites. This shares the workload involved in the manual extraction process whilst still allowing the test to be centralised on one site, leading to improved efficiency. Using CALEX® Extraction Devices We use BÜHLMANN CALEX® Cap devices in order to perform the sample extraction. Once the extracts have been prepared at the Durham site, they are then transported to Darlington ready for analysis. Easier and Safer We find that it is easier and safer to transport the CALEX devices rather than the faecal samples, and the improved stability of the extracted samples (as compared to the primary samples) facilitates this approach. The primary samples are stored for a period of time post-extraction which allows us to go back to them if any issues are encountered during transport or analysis of the extracts. This reduces the need for patients to provide repeat samples. The nature of the extraction procedure means that it accounts for a high proportion of the imprecision for the total assay process. Therefore, it is important that we take this into account when considering how we monitor quality for this assay. UK NEQAS Quality Assessment We participate in the UK NEQAS external quality assessment scheme for Faecal Markers of Inflammation, and the samples provided are extracted on both sites. This is very helpful in allowing us to compare the extraction process cross-site and share best practice. Overall we find that our approach works well and allows us to provide an efficient and high quality service for our patients. Holly Martin, Associate Practitioner, extracting samples at Darlington Memorial Hospital. BÜHLMANN has recently re-evaluated the stability of faecal calprotectin samples within the CALEX device and now recommends a stability of 7 days at ambient temperature. Temperature Recommended Stability Old New Ambient 3 days 7 days 2-8C 6 days 15 days -20C At least 23 months At least 23 months CALEX Extended Sample Stability Short term CALEX Cap Extract Stability at 2-8°C Tested with BÜHLMANN fCAL® turbo Short term CALEX Cap Extract Stability at 23°C Tested with BÜHLMANN fCAL® turbo Time point (days) Time point (days) Concentration [µg/g] Concentration [µg/g] For more information on CALEX Cap faecal extraction for calprotectin and pancreatic elastase please visit: www.calprotectin co.uk/calex

6 LEADING EDGE - 2021-1 The Medical Laboratory Center Dr. Risch is a privately owned group of routine medical laboratories with 14 competence centres across Switzerland and Liechtenstein. It was founded in 1970 by Dr. Gert Risch and is managed today by his sons, Lorenz and Martin Risch. Their core laboratories have held accreditation under ISO/IEC 17025:2017, since 1997. Dr. Jörg Oliver Thumfart, FAMH Clinical Chemistry and Medical Microbiology is Head of Corelab at the company and has recently introduced the BÜHLMANN turbidimetric pancreatic elastase assay alongside the calprotectin assay. “We successfully introduced the automated, turbidimetric assay for faecal calprotectin, the BÜHLMANN fCAL® turbo, on our Roche cobas® c501 in Autumn 2019. The BÜHLMANN fCAL® turbo replaced a classical ELISA assay. The main motivation for this change was to increase flexibility in planning lab work and to avoid having to run samples batchwise on plates. Additionally, the introduction of the ready to use CALEX® Cap device resulted in more stable stool extracts. After the successful establishment of the calprotectin assay and the release of the new turbidimetric pancreatic elastase assay from BÜHLMANN Laboratories AG, it was an obvious step to consolidate those two turbidimetric assays on the cobas® system. Since most of our pancreatic elastase requests from hospitals and general practitioners also include the request for faecal calprotectin quantitation, it was inefficient to follow two different extraction protocols. We could significantly reduce our workload for faecal extraction because with CALEX® Cap the same extract can be used for both analyses. In addition, because the samples could both be run on an automated cobas® system, the turnaround time (TAT) was optimised. We can also run the assays from different locations within our laboratory group. BÜHLMANN fPELA® turbo on Roche cobas® c501 Before implementing the BÜHLMANN fPELA® turbo assay on the cobas® c501, we used a plate-based ELISA solution running on the DSX ELISA robot from Dynex. No major hurdles appeared during the transition process to the new pancreatic elastase assay provider. We started at an early phase when the new assay was not yet IVD certified. Therefore, only a limited amount of performance data was available. With the IVD CE registration of the product by BÜHLMANN in June 2020 this changed, and a comprehensive set of performance data is now available. The BÜHLMANN fPELA® turbo offers a broader measuring range than the ELISA at the higher, normal pancreatic elastase levels, therefore many tested samples with non-pathological levels exceeded the ELISA measuring range and consequently could not be used for the quantitative method comparison. The advantage of the BÜHLMANN fPELA® turbo assay is that less samples require a dilution compared to the ELISA method. The limited measuring range of the ELISA increases the variance of the two assays but also shows the improved performance of the BÜHLMANN fPELA® turbo assay. We highly appreciated that the same medical cut-offs can be applied to both assays. Faecal Pancreatic Elastase BÜHLMANN fPELA® turbo on cobas® c501 Dr. Jörg Oliver Thumfart, Labormedizinisches Zentrum Dr. Risch With the BÜHLMANN fPELA® turbo we see an optimised turnaround time and less preparation efforts are needed. Dr. Jörg Oliver Thumfart

www.alphalabs.co.uk 7 CALEX® Cap for Faecal Extraction For the sample preparation we use the CALEX® Cap extraction device from BÜHLMANN which already has been introduced with the turbidimetric fCAL turbo assay. Pancreatic elastase and faecal calprotectin can be measured from the same extraction, leading to less pre-analytical variation. For faecal sample extraction the CALEX® Cap provides acceptable reproducibility, which is limited due to the heterogenous nature of the sample material itself. The handling of the device is simple, and the extract stability is improved. Also, for the lab technicians it is more convenient to run the extractions with the CALEX® Cap, compared to the former methods used. Expectations of the BÜHLMANN fPELA® turbo In summary, our expectations for the BÜHLMANN fPELA® turbo are fulfilled. We see a shorter turnaround time and less preparation efforts. No interferences to any other assay running on the system or any implausible results have been observed so far. Significantly fewer dilutions are needed and less samples must be reported as “measured higher range”. We can recommend the BÜHLMANN fPELA® turbo due to the easy sample preparation leading to more stable extracts. The analysis with the cobas or a similar system is more flexible, more cost efficient and faster than classical microplate based ELISA assays.” The analysis with the cobas® is more flexible, more cost efficient and faster than classical microplate based ELISA assays. The introduction of the CALEX® Cap device resulted in more stable extracts. Data from historic NEQAS samples shows the BÜHLMANN fPELA gives comparable results to the current ELISA based methods. The BÜHLMANN fPELA gives comparable results when used on different clinical chemistry analysers. Protocols are now available for the Atellica and Alinity instruments. New BÜHLMANN fPELA® turbo Faecal Pancreatic Elastase Assay ■BÜHLMANN fPELA® turbo Runs on main stream clinical chemistry analysers for a simplified workflow and rapid results ■CALEX® sample extraction Utilises the same sample preparation device as the fCAL turbo calprotectin assay. ■Revolutionise your elastase workflow Perform two tests from a single extraction ■Time to first result: 10 minutes ■Dynamic range: 10 - 5000µg/g ■Extraction: CALEX ■Kit size: ~100 tests Contact Alpha Laboratories to find out more. www.alphalabs.co.uk/KK-PELA Find out more at: www.alphalabs.co.uk/kk-pela

8 LEADING EDGE - 2021-1 Why Wait for Results? The Benefits of Rapid and Point-of-Care Monitoring of Therapeutic Drugs Biochemical testing to support clinical decision making is essential, but certain analytes are still not routinely tested in-house. For these, patient samples are sent away to a referral laboratory for analysis or are stored and batch tested once or twice a week. This means that it can take several weeks before a result is available and treatment decisions often have to be made without the benefit of that analyte information. In these situations rapid testing within the laboratory or even Point-of-Care (POC) testing can aid the management of patients significantly, by enabling rapid implementation of the appropriate treatment. In addition to the healthcare benefits, POC testing also gives significant benefits to patients, enabling direct discussion of results and the determination of an appropriate treatment plan immediately. Both of these can significantly relieve patient anxiety that the delays from traditional laboratory testing can cause. Rapid Drug Monitoring Knowledge of serum trough levels for biologic drugs are extremely useful in determining effective treatment. These compounds are prone to either a primary loss of response (up to 30% of patients) or a loss of response over time (up to 46% of patients)1 with the level varying depending on the compound. Historically, testing has been performed using ELISA methods which necessitates batch testing in order to be cost efficient but inevitably introduces a delay in obtaining the result. This is compounded by the fact that few hospitals run the analysis themselves – most use a referral service which means results can be delayed by several weeks. The optimal time to assess a drug level is immediately prior to the next infusion when it is at the trough level. Consequently, due to the time taken to obtain test results traditionally, patients will receive at least the immediate dose without adjustment. They may even receive multiple further doses before the drug can be optimised into the therapeutic window. In a poster presented by C. Rentsch et al. at ECCO 20182, data showed 77% of patients required dose adjustment based on the serum trough levels achieved after the first dose, with 51% requiring dose reduction and 26% requiring dose escalation [Figure 1]. In the absence of timely trough level information these patients are likely to receive subsequent doses without the appropriate adjustment, therefore compounding the situation. Figure 1: Proportion of patients with therapeutic IFX levels increased over time.2 Standardisation There are numerous tests available for the determination of trough level biologics and the World Health Organisation (WHO) has recently introduced an international reference material for infliximab (NIBSC 16/170), to improve comparability of the various testing methods. A poster by Keller et al. presented at the 2020 Virtual UEGW evaluated samples analysed with the BÜHLMANN Quantum Blue Infliximab assay and WHO calibration which showed excellent correlation3 [Figure 2]. Another poster presented at the 2020 Virtual UEGW from R. Olson et al. compared the BÜHLMANN rapid infliximab assay with laboratory HPLC tandem mass spectrometry analysis performed at the Mayo Clinic in America4 with results giving an r of 0.965 [Figure 3]. Figure 2: Passing-Bablok regression analysis of serum samples analysed with BÜHLMANN and WHO calibration.3 Figure 3: Passing-Bablok regression analysis comparing BÜHLMANN rapid infliximab assay with laboratory HPLC tandem mass spectrometry analysis.4

www.alphalabs.co.uk 9 BÜHLMANN Quantum Blue® Therapeutic Drug Monitoring Assays The BÜHLMANN Quantum Blue® Infliximab and Adalimumab assays enable rapid, individual testing of serum samples to give trough level results in about an hour, enabling the proactive management of patients through adjustment of the next dose. Rapid results like these not only enable optimisation of treatment minimising loss of response and side effects but also save valuable healthcare resources. The Quantum Blue therapeutic drug monitoring assays are read using a small bench top reader and can be performed in the laboratory or infusion clinic to give quantitative results. Studies have shown that the results using the rapid method are comparable to the traditional laboratory result: Rapid Test Time The total test time is approximately one hour (actual assay time is 15 minutes). This makes it practical for patients to attend clinic, have their blood sample taken for analysis by the nurse in the infusion clinic and then whilst the patient goes for a cup of tea the assay can be run. The results are then available in time to optimise the dose given at that appointment.Tests can be performed in the laboratory, or by nurses in clinic and still have a good correlation to the laboratory result6. Antibody Testing These drugs can suffer from loss of response due to the development of antibodies against the drug molecules. This can occur in up to 46% of patients (depending on the drug). So, in addition to the importance of determining if the drug level is within the therapeutic window, antibody levels should also be tested. Monitoring patients on treatment is also very important and therefore, anti-drug antibody assays are also available to determine the free antibody level within patients. Following the same format as the drug level assays, the antibody assays will give a qualitative result within an hour enabling immediate adjustment of therapy if required. Flexible There are a number of therapeutic drug monitoring assays available for use with the Quantum Blue reader with individually sealed tests and small pack sizes to suit POC testing. All the Quantum Blue assays offer: ■ Single use tests: □ No need to batch samples □ Individually packaged test to maintain quality until use ■ Simple bench top reader □ Touch screen data entry □ Used as a stand-alone device or connected to a PC/Hospital information system ■ Controls included within each kit ■ High correlation to traditional ELISA methods and WHO standard References 1. G Roda et al. Clinical and translational Gastroenterology 2016. Loss of response to anti- TNFs. 2. C Rentsch et al. ECCO 2018. Pharmacist-led proactive therapeutic drug monitoring with infliximab: utility of and cost-saving with the use of a rapid assay for assessing drug level. 3. E Keller et al. UEGW Virtual 2020. First successful comparison of Quantum Blue rapid TDM assay standardization with WHO international standard for infliximab. 4. R Olson et al. UEGW Virtual 2020. High correlation of the Quantum Blue rapid assay with HPLC tandem mass spectrometry for infliximab therapeutic drug monitoring. 5. Strik. A et al. ECCO 2018. Validation of the Quantum Blue Infliximab level rapid test in clinical practice of patients with inflammatory bowel disease 6. I Lindsjo et al. UEGW 2016. Patient-near infliximab trough-level testing by a novel quantitative rapid test: The Quantum Blue Infliximab test. This rapid test strategy has the potential to reduce patient risks and improve patient outcomes without negative cost implications2 It is a good alternative for the conventional ELISA method for the measurement of IFX serum concentrations at trough in IBD5 Quantum Blue tests can accurately be performed by a nurse which means that TDM now can be moved from a distant laboratory to the near patient facility like the infusion centre and ensure correct dosing in IBD and other patients on IFX treatment6 Quantum Blue TDM Assay Range Code Description Pack size LF-TLIF25 Serum trough level infliximab 25 tests LF-TLIF10 Serum trough level infliximab 10 tests LF-TLAD25 Serum trough level adalimumab 25 tests LF-TLAD10 Serum trough level adalimumab 10 tests LF-ADIF25 Serum trough anti-infliximab antibodies 25 tests LF-ADIF10 Serum trough anti-infliximab antibodies 10 tests LF-ADAD25 Serum trough anti-adalimumab antibodies Coming soon Find out more at: www.alphalabs.co.uk/tdm or contact Alpha Laboratories if you would like to do an evaluation and see how POC testing can impact patient care in your hospital.

10 LEADING EDGE - 2021-1 The ongoing coronavirus pandemic means many patients with inflammatory bowel disease (IBD) are identified as high-risk and need to shield. Thus, any opportunities to prevent the need for them to attend hospital, by offering an alternative for monitoring, should be adopted. Mid and South Essex University Hospital Trust (MSENHSFT) has a catchment population of 1.5 million. The Gastroenterology Department deals with the diagnosis and on-going management of patients with IBD. Patients who are diagnosed need regular monitoring in case of relapse/flare, to ensure ongoing effectiveness of therapy and for funding or cessation of treatments. In early Summer 2020 the department introduced the BÜHLMANN IBDoc® calprotectin home test. This enables IBD patients to test their faecal calprotectin levels in the safety and privacy of their own homes. Results are analysed using the camera and an App on their smartphone and transferred to their clinician for follow up consultation. The team is focused on introducing new technologies to improve patient management and IBDoc filled this requirement. Not just for the immediate crisis but also as a solution that could be sustained for the future as part of an existing strategy. The multidisciplinary clinical team worked closely with patients to introduce them to the technology. The nursing team expanded their telephone clinics and helpline to discuss results and ongoing therapies, thus avoiding the need for many patients to physically attend the hospital. Laboratory Comparisons An important aspect of the implementation was analysis of the patients’ IBDoc results in comparison to professional calprotectin testing in the laboratory. Kezia Allen, Clinical Trials and Informatics, Pathology at MSENHSFT explains “We have always worked closely with our IBD team and this has enabled us to ensure that our assays provide them with the results they need when they need them. We had begun some work looking at the IBDoc last year and the IBD team were keen for the clinical laboratory team to be involved in this. Introduction to Patients Prior to the pandemic, the IBD team had arranged for some patients to attend a workshop, hosted at the hospital, where representatives from Alpha Labs, along with the IBD team and myself from the lab discussed the IBDoc with the patients. Following a demonstration of the device I took the patients to try it for themselves. This was really interesting as it gave me a chance to see how the patients got on using the devices, observe any difficulties and be there to offer advice if needed. The patients found the App and the devices very easy to use and had very few questions (apart from ‘how soon can we have these as part of our standard care!’). For myself from a lab point of view (we often feel a bit of disconnect between laboratory testing and how the results are utilised in the wider healthcare setting) it was so interesting to hear how keen these patients were to be able to better manage their condition themselves at home. Following a successful pilot and with the pandemic ongoing, it became clear that getting the IBDoc devices in use would be key to help keep these IBD patients well and out of hospital during this difficult time. NEQAS We enrolled in the NEQAS faecal markers of inflammation scheme as the first user in the IBDoc group. We have been very pleased with their performance and hope that other users will enrol in the scheme as they begin using the devices for their patients. [Figure1] We will continue to work with the IBD team to refine the service and our use of the IBDoc.” From a clinical perspective Dr Pushpakaran Munuswamy, Gastroenterology, Department Lead at MSENHSFT adds: “The benefit of the IBDoc is the speed with which the result comes through. There is also more engagement both with patients and within the clinical team, because you are able to follow through on a course of action quickly rather than waiting weeks in between decisions which is more frustrating. The IBDoc is very simple but with a lot of impact on patient care.” IBDoc® Home Calprotectin Test Correlation with Laboratory Results Figure 1: EQA data comparing calprotectin concentrations from patient samples tested with BÜHLMANN IBDoc home test and two laboratory assays (BÜHLMANN fCAL® ELISA and BÜHLMANN fCAL® turbo assay on a clinical chemistry analyser). [turbo mean for sample 193B excluded due to reporting error] This correlation is also verified by Mark Busbridge, Biochemistry, Charing Cross Hospital. He is testing samples with both IBDoc and their routine BÜHLMANN fCAL turbo assay on the Architect analyser. He says “This is in support of a study to investigate the use of the IBDoc with Tofacitinib patients, as they require more frequent monitoring than those on other biologic therapies. The results of the IBDoc have shown excellent correlation with the BÜHLMANN fCAL turbo with a mean difference of -5.2% [Figure 2]. Figure 2 Find out more about IBDoc at www.calprotectin.co.uk/ibdoc

www.alphalabs.co.uk 11 Gangliosides, SGPG (glycosphingolipids) and MAG (glycoprotein) are important components of neuronal cell membranes of both, the peripheral and central nervous system. Different antibodies targeting these structures have been found which can cause autoimmune neuropathies. Antiganglioside antibodies can provide better understanding and practical information about the pathophysiology of peripheral neuropathies. While many neural antibodies have been described, only a few of them are diagnostically relevant in specific peripheral neuropathies. BÜHLMANN was one of the first companies who made anti-ganglioside, -MAG and -SGPG antibody IVD tests commercially available and offered such tests to the market. BÜHLMANN are regarded as experts in this field of study and provide a package of sensitive and high quality standardized IVD ELISAs. BÜHLMANN has been at the forefront of neuroimmunology test development for roughly a third of a century, combining innovation with commitment to high quality standards. The first IVD anti-ganglioside antibody ELISA assay was launched soon after studies demonstrated associations of antiGM1 and -GD1b antibodies and acute and chronic neuropathies. Thereafter, BÜHLMANN generated a range of IVD ELISA tests for peripheral neuropathies. Key steps of the development of neuroimmunology ELISAs by BÜHLMANN are presented in the adjacent time line. Today, BÜHLMANN offers a broad portfolio of IVD ELISA tests with the GanglioCombi™ MAG ELISA combining MAG and gangliosides on the same microtiter plate. The GanglioCombi™ Light ELISA offers to test the three most relevant and frequent gangliosides GD1b, GQ1b and GM1. With the anti-MAG antibody ELISA test BÜHLMANN provides an assay characterized by an outstanding sensitivity and specificity which is referred as gold standard by many Neurologists and laboratories to reliably quantify anti-MAG antibodies in immunemediated demyelinating neuropathies. Further, BÜHLMANN offers an anti-SGPG ELISA which enhances the chance to detect all IgM-related neuropathies and an anti-GM1 ELISA which allows individual testing of antiGM1 antibodies of the IgG and/or the IgM isotype.  The History of IVD ELISA Test Development for Peripheral Neuropathies by BÜHLMANN Find out more about the BÜHLMANN range of GanglioCombi™ ELISA assays at www.alphalabs.co.uk/gangliocombi

40 Parham Drive, Eastleigh, Hampshire, SO50 4NU, UK Tel: 023 8048 3000 Email: sales@alphalabs.co.uk Web: www.alphalabs.co.uk Registered in England 1215816 Find out more at www.UN3373.co.uk NewShuttlePouch™ Convenient and Cost-Effective Sample Vial Transport Pouch Innovative, unique secondary packaging solution ■Leak Proof Pouch ■Contains Absorbent Material ■Designed to carry a single 95kPa pressure differential certified blood or any similar sized specimen tube ■Also available to fit a Universal (urine) tube ■Printed with easy to follow illustrated instructions ■Just insert into a rigid outer packaging for a complete and compliant UN3373 solution ■Features easy to open tear area to facilitate processing when the samples arrive at the lab. For more information, to discuss your requirements or request a sample please contact: marketing@alphalabs.co.uk