Leading Edge 2020 Issue 1

2020 Issue 1 Alpha Laboratories Ltd. Diagnostics IN THIS ISSUE ... Improving Workflow for Trace Metals - Zinc 10 New Diagnostics to Help in the Management of Haemophilia 2-3 Investing to Better Support Your Supply Chain 10 Bespoke Patient Packs Help Support Bowel Cancer Testing Progress in the South West 4-5 Supporting Sustainability for All Our Futures 11 Building on the Success of fCAL turbo…with CALEX® Improved Workflow and New Multi Assay Functionality 6-7 Alpha Lab Service Caring for Your Equipment and Your Science 12 QA for Anti-ganglioside Antibody Testing GanglioCombi MAG ELISA Clinical Performance 8-9 Getting to Know You Introducing Gina Sanki - new Technical Specialist 12 Working in Partnership for Earlier Diagnosis

2020 ISSUE 1 2 Welcome to the first issue of Leading Edge in the new decade which introduces you to a number of new products and services. Haemostasis specialists will be very interested in two complementary new kits from Precision BioLogic to help with the management of haemophilia A. The Factor VIII inhibitor testing kit will bring increased confidence in results for a modified Nijmegen-Bethesda assay. Alongside this the Chromogenic Factor VIII Assay provides a reliable testing method less prone to interference (p2-3). Building on the success of the BÜHLMANN fCAL® turbo high throughput calprotectin assay, the new fPELA assay for faecal pancreatic elastase will bring similar workflow benefits. With the ability to use a single patient sample, for both tests from the same CALEX® extraction device, there are distinct efficiency advantages (p6-7). We also launch our new dedicated website www.alphalabservice.co.uk This offers you a single resource for help and advice on the service, maintenance and cleaning of your diagnostic instruments from Alpha Laboratories. You’ll also find access to high quality calibration services for all your pipettes - whatever their brand (p12). The roll out of faecal immunochemical testing (FIT) for symptomatic patient assessment continues to accelerate. Many trusts are eager to share their experience and success and you can read all about the patient and clinician engagement with the South West Cancer Alliance programme on pages 4-5. Quality assessment is vital for diagnostic assays and a recent EQA report (p8-9) for Antiganglioside Antibody Testing verifies the clinical performance of the BÜHLMANN ELISA assays. On pages 10-11 find out how we’ve been investing in improving our warehousing to better support your supply chain and our efforts for environmental sustainability. Plus you can meet Gina Sanki our new technical specialist on page 12. Haemophilia A is a rare bleeding disorder, which affects the ability of person’s blood to clot. The condition is normally inherited and mostly affects males. Haemophilia A is caused by a deficiency in clotting Factor VIII, which ranges in severity depending on the level of clotting factors a person has. Symptoms include prolonged bleeding, bruising easily, and stiff, painful joints caused by internal bleeds. There are roughly 6,000 people affected by this condition in the UK. There are several different treatment options available for haemophilia A. One of the preferred options is to use Factor VIII concentrates, to replace the missing clotting Factor VIII. Factor concentrates are very effective at controlling bleeds and offer patients the opportunity to lead normal lives. Factor VIII Inhibitors In some patients, their immune system doesn’t recognise the factor concentrates (as naturally they produce very little, or no Factor VIII) and responds to it as if it were a foreign protein. In these patients, the immune system begins to produce neutralising allo antibodies, known as inhibitors, against the Factor VIII concentrates. The inhibitors bind to the functional epitopes on the infused Factor VIII concentrates, affecting the function and rendering the factor concentrates treatment ineffective. Screening It’s important to routinely screen patients for inhibitors, so that individuals at risk from developing them can be identified before they become non-responsive to treatment. The development of Factor VIII inhibitors is a significant management challenge for patients with haemophilia A. Inhibitors most commonly occur in those patients with severe haemophilia A. Those with severe haemophilia A have a 25-40% lifetime risk of developing inhibitors, compared to a 5-15% lifetime risk for those with mild to moderate haemophilia A. Most patients who develop inhibitors do so within the first 75 exposures to factor concentrates, with the greatest risk occurring between the first 10-20 treatments. Therefore, it is often children with severe haemophilia that develop inhibitors. Factor VIII inhibitors reduce the effectiveness of factor concentrates therapy. Therefore, it is crucial to precisely quantify inhibitors using methods such as a modified NijmegenBethesda assay. The CRYOcheck Factor VIII Inhibitor kit, manufactured by Precision BioLogic and supplied exclusively by Alpha Laboratories in the UK, is a new way to efficiently and conveniently determine and quantify the presence of functional Factor VIII inhibitors in patient samples. The CRYOcheck Factor VIII Inhibitor kit is a ready-to-use sample preparation kit to facilitate the performance of a modified Nijmegen-Bethesda assay. Increase Confidence in Your Results The kit offers standardised components and a validated protocol, delivering excellent repeatability and reproducibility to reduce intra and inter laboratory variation and increase confidence in your results. New Diagnostics to Help in the Management of Haemophilia Increase Confidence in Your Factor VIII Inhibitor Assay

www.alphalabs.co.uk 3 Printed on Recycled Paper Increased Sensitivity The kit includes all the components needed to prepare your patient samples for a modified Nijmegen-Bethesda assay. The assay recommends using a pre-analytical heat treatment step to inactivate endogenous Factor VIII, helping to increase the sensitivity of the assay. This also means that patients can be tested for inhibitors at any point, regardless of their treatment schedules. Improved Stability Precision BioLogic has validated bovine serum albumin (BSA) as a practical alternative to Factor VIII deficient plasma and has included this alternative in the new kit. BSA improves the stability of the assay, as well as reducing the inter-laboratory variation accumulated from different sources of Factor VIII deficient plasma. The kit includes two additional controls, an inhibitor positive and an inhibitor negative control, adding integrity to the assay and increasing the reliability of your results. Ready to Use Reagents All the components are frozen and ready to use; simply thaw in a water bath and the components are ready to use in minutes! Not only does this save you time, it also eliminates any reconstitution errors. Using frozen components improves laboratory efficiency, saves money, and allows for faster, more accurate results for your patients. Find out more at www.alphalabs.co.uk/cccf08 NewCRYOcheck™ Chromogenic Factor VIII Assay ■Chromogenic assay for the determination of factor VIII activity in human plasma ■Convenient frozen format – ready to use within minutes, no reconstitution errors ■Intended for use on automated coagulation analysers ■Limit of quantification of 0.5% FVIII activity ■Test range of 0–200% FVIII using one standard curve Offers unsurpassed assurance in results, especially in cases of severe haemophilia A. Aids management of haemophilia A in individuals aged two years or older. Studies have shown the chromogenic method to be less prone to interference from lipids or traces of heparin than clot-based FVIII activity tests. Ready to use components Excellent repeatability and reproducibility Reduce inter-laboratory variation Pre-analytical heat treatment step, to inactivate endogenous Factor VIII FACTOR VIII INHIBITOR ASSAY Fresh frozen plasmas are more representative of patient samples and offer faster turnaround times. Due to their frozen nature, these products have a longer shelf life, meaning less wastage from expired product and fewer lot changeovers. Platform Independent The CRYOcheck Factor VIII Inhibitor kit has been designed to seamlessly fit in with your laboratory practices. The kit is platform independent and can be used on any coagulation analyser with any combination of reagents. The Factor VIII activity can be measured using a one-stage clot-based assay or a chromogenic assay. For more information on the new CRYOcheck Factor VIII Inhibitor kit, please visit: www.alphalabs.co.uk/factor-viii or for details on the full range of haemostasis products including CRYOcheck frozen plasmas, please visit: www.alphalabs.co.uk/haemostasis.

4 LEADING EDGE - 2020-1 Cancer is the leading cause of death in the South West. The South West Cancer Network is responsible for working with providers, commissioners and other partners in the new NHS architecture to deliver patient focused improvements in outcomes and experiences. The national cancer strategy; Achieving World Class Cancer Outcomes: A strategy for England 2015 – 2020 set an exciting vision for the transformation of cancer services to radically improve cancer outcomes and to ensure that patients can benefit from high quality modern services. There are six major themes around how this will be achieved, spanning all partners involved in delivering cancer services locally. These are prevention and public health, early and earlier diagnosis, improving patient experience, support to patients living with and beyond cancer, high quality modern services and new approaches to the commissioning and provision of services. Central to delivering this agenda are the Cancer Alliances, as the delivery vehicle for implementing the strategy, meeting the challenges set out in the Five Year Forward View and the local sustainability and transformation plan. The Cancer Alliances in the South West are: Peninsula (covering Devon, Cornwall and the Isles of Scilly) and SWAG (covering Somerset, Wiltshire, Avon and Gloucestershire). In June 2018 the South West Cancer Alliance (SWCA) implemented a faecal immunochemical testing (FIT) service for occult blood. To support its diagnostic pathway for colorectal cancer (CRC), this is aimed at the early detection of CRC in patients classed as “low risk” but not “no risk” . Providing access to FIT testing for General Practice is one of a number of programmes of work aimed at increasing the proportion of cancers diagnosed at an early stage. Now, with data from over 12 months experience of the programme, the SWCA has shared some key points regarding their route to a successful service implementation. The Patient’s Perspective To facilitate the service within SWCA a complete, bespoke, FIT Patient Pack was developed, to provide all the information and materials required by patients - from how to collect their sample, correct labelling, returning their test, to when to expect the results back. Working with the SWCA, the team at Alpha Laboratories designed the patient pack to meet their requirements and necessary logistics. A stock of packs was provided directly to GPs in the region. The GPs then gave one of these, during consultations, directly to individual patients meeting the FIT testing criteria. The patient pack contains; instructions for use (IFU), the sampling device, a test request form, and a sample return mailing envelope. Patient Friendly Sampling FIT requires the patient to perform the sampling at home with the testing device. Collecting a sample with the FIT device is simple and more hygienic compared, for example, to collecting onto a guaiac faecal occult blood card, or providing a faecal sample in a pot. This patient friendly ease of use does help to increase uptake of the test. Bespoke Patient Packs Help Support Cancer Testing Progress in the South West REQUEST FORM TO BE COMPLETED BY GP FAECAL IMMUNOCHEMICAL TEST (FIT) FOR OCCULT BLOOD USE BLOCK LETTERS & BALL POINT PEN Date issued to patient: NHS NO: SPECIMEN: Faecal Sample SURNAME: INDICATIONS - MUST BE COMPLETED A REQUEST WITH NO INDICATIONS OR FROM PATIENTS <50 YEARS WILL NOT BE PROCESSED For use in people who have symptoms that could suggest colorectal cancer, but in whom a diagnosis of cancer is unlikely. Clinical indications defined by NICE in patients without rectal bleeding: Aged over 50 with: unexplained abdominal pain or weight loss Aged 50 - 60 with: changes in bowel habit or iron deficiency anaemia Aged 60 or over and have anaemia without iron deficiency FORENAME(S): MALE FEMALE Date of Birth DD MM YY If preferred use an addressograph label REQUESTED BY: Pathology Sciences Laboratory Southmead Hospital Bristol BS10 5NB Tel: 0117 414 8424 Email: Nbn-tr.nbtfit@nhs.net Website: www.nbt.nhs.uk/FIT_testing Practice Details (Code and Address) R P n a 2 Write your name and date of birth ANDthe date that the sample was taken on the label on the green bag. You may find a way that is easier for you, but make sure you catch your stool sample before it touches the water. 1 Write your name, date the sample was taken AND date of birth on the tube labels as shown here. Start Here... Date of Birth 25.07.1957 H g Name Date of Sample 999XXX 80101274 2099.12.31 M / F A. Sample 20.04.2018 Instructions continued overleaf... NB: Please write the date of sample on the green bag. Patient Instructions for Collecting Your Sample If you would like more information about FIT testing visit www.nbt.nhs.uk/FIT_testing How to Collect Your Sample BEFORE YOU BEGIN.... Your GP has asked you to complete this test. It is important that you do this as soon as possible. Once completed post the kit straight away in the stamped addressed envelope provided. 3 HOW TO CATCH THE SAMPLE It is important that your stool sample does not touch the toilet water. There are different ways to collect your sample, try: A. Several layers of folded toilet paper B. Hand inside a small plastic bag/glove C. A clean disposable container Faecal Immunochemical Test (FIT) Pack Supplied by: Lot no: 230AGD Expiry: 30/04/2019 www.alphalabs.co.uk Ŷ If you are running out of packs email: Nbn-tr.nbtfit@nhs.net to obtain more Ŷ Ensure the issuing of this collection kit is recorded in case the sample is not collected or gets lost in the post DOCTOR PLEASE NOTE : You MUST complete the request form inside this pack, including recording the date it was issued, BEFORE handing over to the patient. Business Reply Licence Number RSAC–SYBY–CLTZ North Bristol NHS Tru t Clinical Biochemistry Southmead Hospital Southmead Road Bristol BS10 5NB TAFDDDDDAFTAAFDDFFTDFTDADATDDTADAAAT HOW to Pl 1. Preparation Write your NAME and Date of Birth on the Green Plastic Bag and Device. Carefully and slowly twist and pull out the Stick Part from Main BODY. H g Name Date of Sample 999123 80101274 2021.12.31 M / F I - E l 999123 2021.12.31 Name Date of Sample 80101274 Name Date of Sample 80101274 Date of Sample 80101274 M / F Date of Sampling (DD/MM/YYYY) NAME Mr Ms Date of Birth (DD/MM/YYYY) / / / /

www.alphalabs.co.uk 5 Printed on Recycled Paper One of the challenges in clinical diagnostics is the logistics of getting a quality sample from the patient to the laboratory for analysis, to minimise pre-analytical variation. Fortunately, the introduction of FIT has vastly improved the method for faecal sample collection. This is an important aspect of the process since the clinical outcomes are dependent on the ability of the assay to detect faecal haemoglobin at very low, versus undetectable concentrations. Based on extensive experience in delivering services for both screening and symptomatic programmes, Alpha Laboratories’ expertise can help support the logistics for providing FIT testing. Find out more at: faecal-immunochemical-test.co.uk However, patients must be clearly instructed on how to collect the stool, and how to sample it with the test device, in order to minimise any pre-analytical variability. There is also the element of the “unpleasant sample”: many patients would often prefer a blood test to a stool test simply because of the nature of the sample and how to collect it. For these reasons, the bespoke IFU was created to help people participate and encourage those who were unsure, to ask for help. The main purpose of the IFU is to; ■ Improve patient acceptance and uptake by using familiar terminology ■ Improve sampling compliance, by combining graphics and text for clarity, to reduce pre-analytical variation ■ Standardise the service to aid data collection and analysis Patient Feedback To help assess the effectiveness of the IFU, plus the patients understanding and receptiveness of the test, a short questionnaire card was also included in the patient pack. This survey method allowed patients to provide their feedback on the service, to help the SWCA ensure they are offering the best service for patients. The questionnaires focused on how userfriendly the test was, and what the patient thought of the end-to-end process. 95% of patients understood their instruction leaflet. 96% knew what to do with their sample once completed. H g Name Date of Sample 999XXX 80101274 2099.12.31 M / F Amy Sample 95% of patients understood their instruction leaflet 96% of patients knew what to do with their sample once completed 92% reported that their GP explained the purpose of the test. This excellent response highlights that most patients found the instructions clear and were able to return the samples without issue. The SWCA also reports that the return rate of the questionnaire card was high; almost all patients who submitted a FIT sample, also included their completed questionnaire card. Primary Care Engagement To further support the service, when it was launched in 2018, Primary Care Engagement events were held. Printed guides were developed for the GPs to aid their decisionmaking process and help them understand the role of FIT in the referral pathway. Patients were also questioned on how well they felt the GP was able to help them; was the test explained, and was the onward pathway outlined to them? 92% of patients reported that their GP explained the purpose of the test. The feedback directly from primary care is also positive. With all surgeries now fully participating in the FIT referral service, it is hoped that this will continue to support the CRC pathway to ensure more cancers are found earlier. This support from primary care is vital to the success of the service. A structured service with engagement from all stakeholders is key to bringing down costs and ensuring effective use of the test – ultimately working to improve the patient experience and outcomes.

6 LEADING EDGE - 2020-1 As you may have seen from the NEQAS reports, the BÜHLMANN fCAL® turbo calprotectin assay is proving very popular, and its use has grown significantly over the last few years [Figure1]. Some of these laboratories were already existing BÜHLMANN calprotectin assay users that have switched technologies from the Quantum Blue® rapid test or the fCAL ELISA. However, a significant proportion are users who have transferred over to BÜHLMANN from other manufacturers kits due to the improved workflow solution that the BÜHLMANN CALEX extraction device combined with the fCAL turbo assay provides. One such user is Mark Busbridge, Lead Biomedical Scientist, Northwest London Pathology, Charing Cross Hospital who shares his experience:   We have been analysing faecal samples for calprotectin in-house since 2011. As with most large multi-site NHS Trusts we have seen a significant increase in calprotectin workload during this period, with the Trust currently processing 70-80 samples per day. Our principle methods have been the Phadia EliA I/II on the ImmunoCAP 100/250 analysers. However, with the increasing sample workload we were struggling to maintain the TAT with our current method, due to prolonged assay time (2 hours), significant ImmunoCAP 250 maintenance downtime and the lengthy sample extraction process. So in 2018 we began investigating alternative methods. The BÜHLMANN fCAL® turbo calprotectin assay was selected, as this can be run on one of our principle analysers (Abbott Architect C8000). The BÜHLMANN CALEX extraction device process is simple and straightforward for staff to follow, resulting in a much improved workflow compared to the previous method, allowing more staff flexibility in this section. Since going ‘live’ with the method in late 2019, we have noted improved precision in our inter batch re-extracted patient QC samples, good sample linearity and excellent repeatability and we are currently observing good agreement with our EQA method mean group. Mark Busbridge, Lead Biomedical Scientist, Northwest London Pathology, Charing Cross Hospital Building on the Success of fCAL turbo… CALEX® Cap Brings Improved Workflow and New Multi Assay Functionality Figure 1 : Number of routine BÜHLMANN fCAL turbo users on the November NEQAS scheme.

www.alphalabs.co.uk 7 Printed on Recycled Paper Many laboratories are using the fCAL turbo on main stream clinical chemistry analysers (Abbott, Beckman, Roche and Siemens). There are also stand-alone options available which give laboratories the flexibility to choose how and where they want to run their assays. All sites in the UK are using the assay in conjunction with the CALEX extraction device as this offers the best workflow solution in today’s busy laboratories. Faecal Pancreatic Elastase Building on the success of the fCAL turbo assay, BÜHLMANN is launching its new fPELA assay for faecal pancreatic elastase. This will enable patients and pathways to benefit from the same workflow improvements that calprotectin has. With protocols available for many standard clinical chemistry analysers the BÜHLMANN fPELA is set to revolutionise faecal elastase testing. Pancreatic Insufficiency Pancreatic insufficiency is the reduction of production or transportation of the pancreatic enzymes. This results in the inability to properly digest fats, proteins or carbohydrates. It causes patients to suffer from a range of gastric symptoms including abdominal pain, weight loss, diarrhoea and loss of appetite. These symptoms can be confused with a variety of other gastric complaints; so performing a simple stool test to determine the level of pancreatic elastase helps with the diagnosis of this condition. Clinicians then just need to determine the cause…… Pancreatic insufficiency really is just another symptom but the cause is almost always pathogenic, resulting from conditions such as chronic pancreatitis, cystic fibrosis, diabetes mellitus, Crohn’s disease, pancreatic cancer, as well as a variety of other conditions. Pancreatic elastase is fairly stable in stool samples and so the levels of this are used as a marker to determine pancreatic activity as a whole. Multiple Assays from a Single Sample Extraction The new BÜHLMANN fPELA assay utilises the same CALEX extraction device as the fCAL turbo calprotectin assay, so it is possible to run both tests from a single tube. The CALEX is loaded straight onto the analysers without further diluting or decanting of the sample. Fast Turnaround With a time to first result of 10 minutes and further results following every few seconds thereafter, it is certainly one of the fastest faecal elastase assays available. Combine this with random access and no requirement for specific batch sizes you can easily see how this can improve the elastase service that is provided to clinicians, helping to quickly diagnose and support patients with pancreatic insufficiency. The assay has a standard range of 10 – 500µg/g, although the sample can be diluted to give values up to 5000µg/g if you want to find the best functioning pancreas! There is no interference with the results from Pancreatic Enzyme Replacement Treatments (PERT), so there is no need for patients to alter their therapy/diet before a test. Calibration is stable for around two months and reagents have an open on-board stability of about 2 months. The kits contain enough material for approximately 100 tests, however, this will be analyser dependent. Data from historic NEQAS samples shows the new BÜHLMANN fPELA gives comparable results to the current ELISA based methods [Figure 2] If you would like to evaluate the new BÜHLMANN fPELA Faecal Pancreatic Elastase assay then please contact senior product manager Amanda Appleton (aappleton@ alphalabs.co.uk) or your local Key Account Manager who can arrange this for you. Find out more about the BÜHLMANN range of calprotectin assays and CALEX extraction device at www.calprotectin.co.uk Figure 2 : NEQAS data shows the new BÜHLMANN fPELA gives comparable results to the current ELISA based methods.

8 LEADING EDGE - 2020-1 Testing for Autoantibodies There are two laboratory methods available to test for these autoantibodies; an ELISA (both in-house and commercial methods are available) and line/dot-blot (commercial methods are available). The GanglioCombi MAG and the GanglioCombi Light ELISAs from BÜHLMANN allow for the detection of autoantibodies in serum samples from patients with suspected peripheral neuropathies. The GanglioCombi MAG ELISA allows for the detection of anti-GM1, anti-GM2, anti-GD1a, anti-GD1b, anti-GQ1b and anti-MAG, testing the reactivities to IgG and IgM as a mix and separately. The GanglioCombi Light ELISA detects anti-GM1, anti-GD1b and anti-GQ1b, again with the option of using an IgG/IgM mix or separately. Due to the glycosphingolipid nature of the antigens, it makes it difficult to extract, purify and use them to devise completely reliable testing methods; it’s accepted that most methods, both ELISA and line/dot-blot, tend to perform sub-optimally. EQA Scheme An External Quality Assessment Scheme (EQAS) on anti-ganglioside antibodies, supported by the Italian Association of Neuroimmunology, was published in 2018. The EQAS collected results from 15 participating laboratories in Italy, all using a variety of testing methods (commercial and in-house ELISAs, several different commercial line/dot-blot). The laboratories were asked to analyse five anonymised serum samples, from clinically well described patients. ■Sample 1: sensory-motor Guillain-Barré syndrome (GBS) ■Sample 2: GBS ■Sample 3: IgMκ monoclonal gammopathy-associated polyneuropathy (anti-MAG antibody negative) ■Sample 4: CANOMAD syndrome (Chronic Ataxic Neuropathy, Ophthalmoplegia, Monoclonal IgM protein, cold Agglutinins and Disialosyl antibodies) ■Sample 5: multiple mononeuropathy QA for Anti-ganglioside Antibody Testing Anti-ganglioside antibodies are used in the differential diagnosis of suspected immune-mediated neuropathies. More than 20 antiganglioside antibodies act as possible biomarkers of disease in inflammatory axonal neuropathies; currently, only a few of these antiganglioside antibodies are associated with well-defined clinical phenotypes. Good medical practice recommends testing for these associated antibodies only when inflammatory neuropathies are suspected. Table 1 depicts which anti-ganglioside antibodies are most prevalent in some autoimmune neuropathies. Table 1 : Most Prevalent Pathologies and Interpretation of Autoimmune Neuropathies Ref; BÜHLMANN

www.alphalabs.co.uk 9 Printed on Recycled Paper In addition, each laboratory was given a further two anonymised control sera from healthy donors. The laboratories tested each sample for anti-GM1, anti-GM2, anti-GD1a, anti-GD1b, anti-GD3, anti-GQ1b, anti-GT1a, anti-GT1b; all antigens were tested for IgG and IgM reactivities. Of the 15 laboratories involved, one of these was using the BÜHLMANN GanglioCombi Light ELISA, a further six laboratories were using in-house ELISAs, and the remaining eight laboratories were using line/dot-blot methods from various manufacturers. The results obtained for sample 1 across the 15 laboratories are shown in Table 2. Laboratory Assay GM1 GM2 GD1a GD1b GQ1b GT1a 1 ELISA - BÜHLMANN GanglioCombi Light Positive 2 ELISA (in-house) False Negative False Positive False Positive 3 ELISA (in-house) False Negative 4 ELISA (in-house) False Negative False Positive 5 ELISA (in-house) False Negative 6 ELISA (in-house) False Negative 7 ELISA (in-house) False Negative 8 Line/dot-blot (Dotzen/Zentec) False Negative 9 Line/dot-blot (Dotzen/Zentec) False Negative 10 Line/dot-blot (Dotzen/Zentec) False Negative 11 Line/dot-blot (Euroimmun) False Negative 12 Line/dot-blot (Euroimmun) False Negative 13 Line/dot-blot (Euroimmun) False Negative 14 Line/dot-blot (generic assays) False Negative 15 Line/dot-blot (generic assays) False Negative False Positive Table 2 : Comparison of anti-ganglioside patient test result across different laboratories and assays Expected anti-ganglioside antibodies: GM1 IgG Sample Expected Autoantibody Profile Labs performing line/dotblot Labs performing in-house/ commercial ELISAs BÜHLMANN GanglioCombi ELISA 2 anti-GM1 IgG 3/7 3/7 13/13 3 anti-GD1b IgM & anti-GQ1b IgM 7/7 5/7 13/13 4 anti-GQ1b IgM 5/7 4/7 13/13 Table 3 : Which methods obtained the correct autoantibody profiles? Based on the clinical phenotype of the patient providing sample 1, you would expect a positive result for the anti-GM1 antibody only. The collated results show that the GanglioCombi Light ELISA, manufactured by BÜHLMANN, was the only testing method to produce the expected result. All the other test methods had a false negative result for anti-GM1, and there were a few false positive results for some of the other methods. In addition to this, 13 of these laboratories were given the opportunity to test the same samples with the BÜHLMANN GanglioCombi MAG ELISA. The purpose of this was to evaluate the inter-laboratory variability for the assay. The results showed 100% concordance between the 13 laboratories for sample 2 (anti-GM1 IgG positive), sample 3 (anti-GD1b IgM positive), sample 4 (anti-GD1b IgM & anti-GQ1b IgM positive), and sample 5 (all negative). Further to the excellent inter-laboratory variability demonstrated, the GanglioCombi MAG ELISA performed well when evaluated against the clinical phenotype of the patients providing the samples. Table 3 shows the expected autoantibody profile for samples 2, 3 and 4, and how many laboratories, using each method, managed to obtain the correct result. All 13 laboratories using the GanglioCombi MAG ELISA obtained the correct results for samples 2, 3 and 4; the GanglioCombi MAG ELISA outperformed the other methods being used (line/dot-blot and in-house ELISAs), as not all laboratories using these methods obtained the expected result. Reference View the full EQAS report: Franciotta et al. Anti-ganglioside antibodies: experience from the Italian Association of Neuroimmunology external quality assessment scheme. Clin Chem Lab Med 2018; 56(11): 1921–1925. https://doi.org/10.1515/cclm-2018-0234 For more information on the BÜHLMANN neuroimmunology kits please visit www.alphalabs.co.uk/neuroimmunology

10 LEADING EDGE - 2020-1 To better support our customers’ supply chain and with improved efficiency and sustainability in mind, Alpha Laboratories has made significant investment in its warehousing infrastructure over the past 18 months. Growth, and provision for BREXIT, has required increased storage and we have expanded our warehousing with the reclamation and renovation of an adjoining warehouse unit. We have also invested in our current facilities, upgrading and refurbishing the existing warehouses. All units have benefited from additional storage racking and shelving, new floors and monitoring equipment, and our capacity for cold storage has more than doubled. These improvements mean that we can hold more stock on-hand, helping us to meet our goal of next day delivery for in-stock items. Alongside this we have also developed an additional, temperature monitored, narrow aisle warehouse with additional cold storage facilities. This new warehouse facility is dedicated to fulfilling supply for our customers within the national Bowel Screening Programmes. It provides both ambient and 2-8°C facilities for storage of the reagents and sample devices for the new faecal immunochemical test (FIT) screening method. The narrow aisle design allows for the most efficient use of the space. The unit is temperature monitored 24/7 with an external monitoring company. A major initiative, requiring funding of more than £150K, has seen the replacement of the standard roofing with an advanced Trisomet® trapezoidal roofing system. This provides greatly improved thermal insulation according to DIN EN 14509 to reduce heat loss. The roof installation also comprises 15% insulated skylights across the warehouse areas, which means using the natural daylight is sufficient for much of the year. The investment and expansion of our infrastructure has been supported by the growth of the warehouse team and will enable us to continue to provide a quality service to our customers, ensuring that their orders are prepared and delivered to a high standard. Investing to Better Support Your Supply Chain Improving Workflow for Trace Metals - Zinc Zinc deficiency is not always easy to diagnose, it affects many organ systems and there is not a single distinct symptom. Symptoms may include delayed wound healing, impaired taste, loss of appetite, hair loss, fertility issues, skin roughening and increased susceptibility to infection. Zinc is an essential trace element and the second, (iron being the first), most abundant transition metal found in living organisms. It has essential roles in metabolic pathways concerning protein, lipid carbohydrate and energy metabolism. Zinc is also involved in cell division, vital for growth and tissue repair. High concentrations are found in the placenta and umbilical cord during pregnancy where it promotes foetal development. Deficiencies in childhood can result in growth retardation and deficits in cognitive and motor development. Zinc is also important for reproductive health, it is needed to maintain normal levels of testosterone and deficiency can lead to delayed sexual maturation, infertility and impotence. The prostate gland requires high concentrations of zinc for correct functionality and the zinc concentration found in seminal fluid can be indicative of sperm quality. The immune system is also dependent upon zinc for normal development and function. Zinc ions are involved in regulating intracellular signalling pathways in innate and adaptive immune cells. Zinc deficiency negatively impacts various neutrophil functions including phagocytosis, oxidative burst, degranulation, cytokine production, and chemotaxis. Maturation and function of T and B cells are also affected and a disturbed ratio of Th1 and Th2 cells may be observed that favours Th2-driven allergic reactions. Zinc deficiency may be associated with other health issues such gastrointestinal diseases like ulcerative colitis or Crohn’s, chronic liver or kidney disease, diabetes and sickle cell disease. It can also be the result of diet or lifestyle. It is one of the more common deficiencies seen in poorly planned vegetarian and vegan diets; high cereal protein intake which is rich in phytate may reduce zinc bioavailability. Deficiency is also seen in cases of alcohol dependency where zinc absorption is decreased whilst urinary zinc excretion is increased. It is also common observed in the elderly population and significant parallels between the changes described in immunosenescence and those associated with zinc deficiency such as reduced thymus activity and hormone production, decreased response to vaccines and reduced phagocytic and NK Cell function. The Sentinel zinc assay is suitable for use with serum, plasma and seminal fluid enabling analysis for numerous diagnostic investigations. Whilst some traditional assays for zinc require a deproteinisation step, the Sentinel assay offers improved workflow as there is no need for such pre-treatment. This dual reagent system has a measuring range of 5-2000µg/dL and on-board stability of 30 days. To find out more about the Sentinel zinc assay please visit www.alphalabs.co.uk/17640H

www.alphalabs.co.uk 11 Printed on Recycled Paper Supporting Sustainability for All Our Futures Alpha Laboratories is committed to innovative sustainability practices focused on building a better world for future generations. We are changing the way we do business to preserve natural resources and the environment, by reducing waste and reusing or recycling materials, when possible. We focus on diminishing our consumption of natural resources, using sustainable options and striving to improve our environmental performance. This covers all aspects of our business from reduced use of energy, paper and printing, to a car fleet that is converting to electric and hybrid vehicles. We use the minimum amount of packaging to ensure our products arrive to you in good condition and use recycled materials wherever possible. Partnering with our customers is paramount to meeting our sustainability goals. We aim to help you by providing more eco-friendly products, manufactured with renewable energy. Our popular recycling scheme for customers turns your used laboratory plastics back into something equally useful, while reducing the environmental impact of plastic manufacturing. Campaigns such as the LaboraTree tree planting scheme create a positive impact, enabling us to all put something back into the environment. Greener Manufacturing There is no other material that has transformed the world as dramatically over the last century as plastic. Yet over the past 20 years it has become a growing environmental concern. However, plastic consumables play a vital part in science, medical research and healthcare. Without them we wouldn’t have the knowledge, technologies, products and medicines we all rely on. We work closely with suppliers to source products that are manufactured in an eco-efficient manner. For example our leading pipette tips and centrifuge tubes are manufactured in a facility that has taken action to operate with minimal environmental impact. This production facility uses a rooftop solar power array, energy efficient moulding machines and a closed-loop water cooling system. The internal recycling programme results in zero plastic waste and E-beam sterilisation produces no radioactive waste. Greener Packaging and Distribution We always want to ensure our products arrive to you in the best possible condition. We use a range of right-sized, sustainable and durable packaging materials dependent on their suitability for the goods being shipped. We use the most environmentally friendly packaging method available, choosing reuse and recycled materials as the primary option. Wherever possible we reuse boxes that we have received goods in from our suppliers, for shipments out to you. If using new boxes they are made from 70% recycled cardboard. To maximise their durability the outer shell is made from stronger new material, but this comes from sustainable managed sources. We always use the minimum amount of packaging possible but when void fill is necessary, to protect your products in transit, we use sustainable fan folded paper stuffing. This is from FSC certified suppliers with climate neutral production. Frozen or cold items require special treatment to maintain their integrity. We use small amounts of bubble wrap for these products. Insulated boxes are reused and our own solution consists of a lined cardboard container that minimises styrofoam use whilst providing adequate insulation. We are constantly reviewing our packaging materials to achieve the most sustainable solutions that provide the best performance. We work with a courier who pursues efficiency and invests in alternative fuel and advanced technology vehicles to pioneer more sustainable solutions with lower environmental impacts. Office Practice In all aspects of our office, warehouse and field based environments staff are trained and equipped to follow green working practices and to always aim to Reduce, Reuse and Recycle. Active changes to working processes are reducing the use of printing inks and paper consumption. Employees are encouraged to manage heating and lighting efficiently in their work areas. Recycling All employees are requested to separate all recyclable waste. This is now processed by a local handling agent to minimise transportation to the recycling depot. Travel Through a transition from petrol and diesel vehicles to a fully electric and hybrid fleet we have reduced CO2 emissions by 32% and are focused on improving this further with each vehicle replacement. Air travel has been reduced to fulfill essential requirements only and greater use of technology is enabling more business meetings and training to occur online, with minimal environmental impact. Marketing The increased use of advanced digital communications means we can keep you up to date with market developments, new solutions, product innovations and special offers, through our websites, emails and social media. Our online literature library provides a wealth of digital brochures, technical documents and case studies that can be downloaded direct to your PC or mobile device. However, we still feel there is a place for occasional print publications that can be reviewed offline at leisure. We have taken steps to reduce the environmental footprint of our popular periodicals such as Leading Edge and LabVantage by now printing them on recycled paper and mailing them without any outer packaging. These ‘naked’ mailings save over 100kg of plastic annually. We also offer free reusable customer gifts, many made from recycled materials. Request your reusable water bottle, coffee cup or shopping bag. to reduce plastic waste and environmental impact in your daily activities. Find out more at: www.alphalabs.co.uk/sustainability

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 LEADING EDGE - 2020-1 If undelivered please return to 40 Parham Drive, Eastleigh, Hampshire, SO50 4NU The success of your application is highly dependent on the quality and performance of the instruments that you use for your science. But just as important is choosing a professional service partner with a consultative approach to solving your service and maintenance needs. Such a partnership will give you confidence in your results and ensure your compliance with regulatory requirements. Alpha Laboratories’ dedicated Service Technicians are on hand to fix and maintain your laboratory equipment to the highest levels. The regular service and maintenance of diagnostic laboratory equipment is essential to ensure the quality of clinical results. It also minimises the risk of unplanned downtime and interruption of workflow, helping you to provide the best possible pathology service. However, with routinely used equipment there may be times when something needs urgent attention and our team of skilled technical experts are on hand to come to your rescue. You can trust Alpha Laboratories to take care of your instrument service and repair needs, giving you the confidence in the results you provide to your clinicians and patients. We provide expertise for the HM-JACKarc FIT analyser, the Dynex DS2 ELISA processor and the BioData PAP-8E platelet aggregometer. We also provide expert pipette service and calibration carried out by Sartorius, our ISO 17025 accredited partner. Visit our dedicated new website www.alphalabservice.co.uk to find out more. Here you will find: ■ Useful documentation to support your instruments including operation guides ■ Advice on choice of calibration and service levels for pipettes ■ FAQs ■ Service request and decontamination forms Expanding our team of Technical Specialists, Gina Sanki has recently joined Alpha Laboratories. Gina brings a wealth of experience gained working within the NHS, as she explains: “ I graduated from Cardiff University in 2009 with a BSc (Hons) in Biochemistry. Following this I worked briefly as a HTO in the NHS Blood and Transplant centre in Bristol, then took a few months out to go travelling around Costa Rica. On returning to the UK I began a four year training post in the NHS as a Clinical Biochemist (including an MSc in Clinical Biochemistry) and was fortunate enough to then gain a substantive post at the end of my training. I then worked as a Senior Clinical Biochemist for the following five years. I am looking forward to my new role, and I hope that working in the NHS for the past nine years will enable me to provide experienced support to Alpha Laboratories’ customers. Sports I have a slightly different sporting hobby, I train in static trapeze! It’s a great way to keep fit and I have been able to perform at one open air event in Wales so far, but hopefully I will be able to perform more in the future. As well as trapeze, I also compete and train in agility with my two dogs; a Jack Russell Terrier called Stewie and a large Lurcher cross called Ollie; we are only in the early stages of competing and it’s all about the fun for us. Pets Together with my two dogs, I also have two cats; a Bengal called Zac and a rescue called Milo. Surprisingly all four animals get on very well and can quite often be found sleeping together on the sofa. Food I like a variety of food, in particular Lebanese if eating out for special occasions. I also like to bake for friends and family, and a favourite with them is my courgette and lemon cake (tastes better than it sounds!). Favourite Film I love a good cartoon film, with most Disney/ Pixar films being in my top 10. Coco is a particular favourite at the moment, although I may be slightly biased as the main canine character has a strong resemblance to my Lurcher!” Getting to Know You