Leading Edge 2022 Issue 1

IN THIS ISSUE ... Welcome 2 Upcoming Events for 2022 10 Neonatal Hyperbilirubinaemia Confident Analysis Even With Haemolysed Samples 2-3 The Clinical Challenges of Sepsis New MDx-Chex™ Control for BCID2 11 FIT Service Wins Partnership with the NHS Award 4-5 Improving Workflow of Trace Metals Assays for Zinc, Magnesium and Copper 12 Outsourcing Calprotectin Stool Pre-analysis to the Patient’s Home 6-7 APTT Testing Results Enhanced Convenience and Increased Confidence 13 Reducing the Volume of Single Use Plastic with the Award-Winning ShuttlePouch™ 8-9 Sustainability Snapshot Growing Our Efforts in Environmentally Friendly Practices 14-15 New Presentation Format for UK NEQAS 10 Turbo Charge Your Faecal Testing CALEX Faecal Extraction for both Calprotectin and Elastase 16 2022 Issue 1 Alpha Laboratories Ltd. Diagnostics

2 2022 ISSUE 1 The end of 2021 was a time for great celebration at Alpha Laboratories with some exciting live events. Our teams were invited to attend two award ceremonies and from both we came away with the winners accolade. Firstly, we joined our partner ShuttlePac Ltd. at the UK Packaging Awards where their innovative, specimen transport pouch, ShuttlePouch™ received “Flexible Plastic Pack of the Year”. The judges recognised that the ShuttlePouch™ substantially reduces plastic use compared to other conventional biohazard bags. Along with other benefits such as the combined fixed absorbent material and anti-injury rounded corners, it was pronounced a “worthy winner”. To win against a list of highly regarded companies in the category was indeed an honour. You can read all about the benefits of ShuttlePouch on pages 8-9. A month later, together with the Clinical Biochemistry team from Cwm Taf Morgannwg University Health Board, we received the “Partnership with the NHS” title at the MediWales Innovation Awards. This was in recognition of the successful introduction of a quantitative Faecal Immunochemical Test (FIT) service to help identify patients with colorectal disease who need urgent referrals. Read the full story on pages 4-5. Part of the successful roll out of this service is the logistics for making sample collection and return simple and convenient for patients. This is something consultant clinical biochemists at Monklands Hospital also recognised as an important requirement for their calprotectin service during the pandemic. Discover how they have successfully outsourced faecal sample preparation direct to the patient using the BÜHLMANN CALEX collection and extraction device. See pages 6-7. Alongside these informative articles this issue also brings announcements of new products, our ongoing environmental efforts, plus the live events we will be at during 2022 - we hope to see you there! Neonatal Hyperbilirubinaemia Confident Analysis Even With Haemolysed Samples Neonatal jaundice is a common condition. In most cases, it will be caused by a transient increase in unconjugated (indirect) bilirubin, due to the immaturity of the neonatal liver and increased haem turnover. This ‘physiological’ jaundice may resolve spontaneously, but close monitoring is necessary as high concentrations of unconjugated bilirubin can present a risk of brain damage. Rapid treatment with phototherapy or exchange therapy must be implemented if threshold concentrations of total bilirubin are exceeded, as detailed in NICE Clinical Guideline CG98. Unconjugated or Conjugated Bilirubin Conjugated hyperbilirubinaemia in neonates is never physiological and always requires further investigation. The ratio of conjugated or direct bilirubin (DBIL) to total bilirubin (TBIL) can help determine if the hyperbilirubinaemia is the result of predominantly unconjugated or conjugated bilirubin and facilitate clinical interpretation. Whilst reporting a bilirubin ratio is the ideal, there are certain situations where limited sample volume does not permit analysis of both and may result in a request for DBIL only. As detailed in the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) guideline “Investigation of Neonatal Conjugated Hyperbilirubinaemia”, if conjugated bilirubin level is > 25 µmol/L and/or >25% of the total bilirubin, the infant should be investigated promptly for possible underlying liver disease. Although diazo-based methods for bilirubin determination are widely used, these can be prone to negative interference from haemoglobin and, when presented with haemolysed samples there is a risk that results below the true concentration may be reported. Haemolysis High levels of haemolysis are not uncommon in neonatal samples, which can make paediatric patients particularly vulnerable when assays have significant interferences from haemoglobin.

www.alphalabs.co.uk 3 Vanadate Oxidation Method Wako’s method for bilirubin determination was developed to address some of the common interferences and is unaffected by haemoglobin up to 500 mg/dL. It delivers reliable results from haemolysed specimens, negating the need to reject samples. Introducing Wako’s direct bilirubin assay could help improve your laboratory service and facilitate patient management, by helping to avoid diagnostic delays and unnecessary repeat sample collection. Since traditional diazo methods are often subject to interference from haemoglobin, they create a risk of reporting values below the true concentrations. Therefore laboratories may find themselves rejecting a significant number of samples which exhibit haemolysis. This problem is most commonly seen in paediatric samples and can impact the care of this vulnerable patient group. Rejection of haemolysed samples necessitates additional specimen collection from the patient. The Wako Direct Bilirubin assay is not significantly affected by haemolysis up to an index of 800: levels that are commonly seen in neonatal samples. The use of this assay prevents rejection of samples as unsuitable for analysis and has been adopted by many laboratories. Within the Wako Assays Bilirubin is oxidised to biliverdin and the change in absorbance as measured in the yellow part of the spectrum is used to calculate the bilirubin content of the sample. Both Direct and Total Bilirubin assays provide excellent performance with minimal interference, delivering clear, reliable answers when it matters. References: www.nice.org.uk/guidance/cg98 www.old.bspghan.org.uk/sites/default/files/ guidelines/2016_guideline_for_the_investigation_ of_neonatal_conjugated_jaundice.pdf Hb (mg/dL) Hb (mg/dL) For more information, visit our website alphalabs.co.uk/bilirubin Direct and Total Bilirubin Use Assays with Confidence  No interference from Ascorbic Acid up to 50mg/dL  No interference from Haemoglobin up to 500mg/dL  Direct Bilirubin: linear to 20mg/dL (342µmol/L)  Total Bilirubin: linear up to 40mg/dL (684µmol/L)  Ready-to-use liquid stable reagents  Open-vial stability 30 days at 2-8C  Standardised to SRM916a (NIST)

4 LEADING EDGE - 2022-1 On Thursday 2nd December 2021, at the Annual MediWales conference in Cardiff, Alpha Laboratories was declared the winner of the Partnership with NHS Award, sponsored by the Life Science Hub. This was in recognition of the industry partnership with the Clinical Biochemistry team at Cwm Taf Morgannwg University Health Board (CTMUHB), resulting in the successful rollout of their symptomatic Faecal Immunochemical Testing (FIT) service. In 2018, Alpha Laboratories was the industry partner for CTMUHB Clinical Biochemistry team’s application for the Health Technology Award from the Bevan Commission. This allowed the Clinical Biochemistry department to develop a symptomatic FIT service, originally planned for rollout to primary care users in line with NICE DG30 guidance. The Clinical Biochemistry team from CTMUHB contacted and received feedback from several patient groups including Voluntary Action Merthyr Tydfil, North Wales Cancer Patient Forum, Macmillan Cancer Support and Cancer Research UK. Developed with Patient Feedback Patient feedback was important to ensure that the patient packs developed in partnership with Alpha Laboratories were acceptable to the target patient group. These packs include the sample collection device alongside bespoke Instructions For Use and Patient Information Sheets designed to encourage compliance and correct undertaking of the test. Following the patient feedback Alpha Laboratories then worked in partnership with the Clinical Biochemistry team to develop a pack which met their requirements. Demonstration patient packs were provided to enable the Clinical Biochemistry team to present to the Primary Care cluster group meetings. Bilingual All Wales documentation was then created for use in the patient packs. HM-JACKarc Analyser The FIT test was established and verified using the HM-JACKarc analyser in CTMUHB and was accredited by the United Kingdom Accreditation service (ISO 15189) in November 2018. Throughout this partnership, Alpha Laboratories has provided additional support for the pilot GP project, alongside ongoing service and application support for the full service roll out across several health boards who use the analytical service provided by CTMUHB. Since becoming fully UKAS accredited CTMUHB now runs FIT samples using the HM-JACKarc analyser provided by Alpha Laboratories for the Cwm Taf Morgannwg area, Swansea Bay UHB, Hywel Dda UHB, and the Swansea based CRaFT Study. Supporting Decreased Endoscopy Capacity In addition to the use of symptomatic FIT in primary care, FIT has also been used during COVID-19 to help support decreased endoscopy capacity. By using FIT to triage patients it can help reduce colonoscopy waiting lists, and by directing patients to more appropriate management e.g.outpatient review and more recently, the urgent cancer pathway and rapid diagnostic clinics. Partnership with the NHS Award In recognition of the successful rollout of the symptomatic Faecal Immunochemical Testing (FIT) service at Cwm Taf Morgannwg University Health Board Annual MediWales Innovation Awards Winners

www.alphalabs.co.uk 5 Multi-disciplinary Collaboration Professor John Geen is the Clinical Lead for Cwm Taf Morgannwg University Health Board’s Clinical Biochemistry Service. In conjunction with clinical colleagues in Gastroenterology, Surgery, Endoscopy and Primary care they have taken a multi-disciplinary and multi-professional approach to the implementation of FIT in the Symptomatic Service at CTMUHB. “The collaborative approach taken in the development of the FIT service has been possible through the shared values, aims and objectives of the whole team. Good communication and a shared enthusiasm for this important development from all stakeholders was a key factor. Through a laboratory based project, the input from patients and the third sector in the development of the information and guidance shared with the patients was also critical to include a bi-lingual approach. The interpretation of the FIT result and the subsequent patient management has been optimised through the development of robust local diagnostic pathways and integrated safety netting. These were co-produced across Cwm Taf Morgannwg being cognisant of the recommended clinical guidance to include the “National Framework for the Implementation of FIT in the Symptomatic Service” in Welsh Health boards (March 2021). Through team working, a robust and resilient Symptomatic FIT service has been developed at Cwm Taf Morgannwg University Health Board”. Best Service to Patients The FIT service in CTMUHB is run by a great team all working together to provide the best possible service to patients. Jaynion Hampton is the FIT coordinator at CTMUHB. “As the FIT coordinator in Biochemistry CTMUHB I organise the FIT process from beginning to end. This includes monitoring the email accounts where primary and secondary care patient FIT request forms are sent to and arranging for FIT packs to be sent out directly to the patient. If a FIT sample has not been returned within 2 weeks the requestor is then notified via email to query the delay in receiving the completed sample back from the patient. Once the samples are received, they are booked onto the LIMS and analysed on the HM-JACKarc system. All results >10 ug/g Hb are emailed directly to the Integrated Locality Group (ILG) specific endoscopy unit to be acted upon urgently. I am proud to be part of the CTMUHB FIT service that aids in the early diagnosis of colorectal cancer in patients” Kirsty Holloway is the Special Chemistry Section Leader at CTMUHB. “As the senior biomedical scientist in charge of special testing at CTMUHB, part of my role is to oversee the daily processes involved in FIT testing carried out by our FIT coordinator Jaynion. I make sure that all internal and external quality controls analysed are within an acceptable range which confirms the reliability of results being sent out to patients. I also ensure that Jaynion has all the stock required to run the HM-JACK smoothly by placing orders with Alpha Laboratories” References: National Endoscopy Programme. National Framework for the Implementation of FIT in the Symptomatic Service. For Welsh Health Boards: 17.03.21; Version 1. Founded in 1992, MediWales is the independent life science network for Wales, a not-for-profit limited company. Working on behalf of the Welsh life science sector, creating business opportunities and partnerships for their members, supporting global trade development, improving access to vital clinical expertise and engaging with government to align support with sector needs. They support over 180 members from the medical technology, diagnostic and pharmaceutical industries, NHS health boards, university departments and professional services and suppliers. 2021 marked the sixteenth MediWales annual awards ceremony and conference. For more information, visit our website faecal-immunochemicaltest.co.uk Jaynion Hampton - FIT coordinator sending out the FIT patient packs Jaynion Hampton - FIT coordinator running the HM-JACKarc analyser Kirsty Holloway - Senior Biomedical Scientist, Special Chemistry Section checking the accuracy of internal quality control and patient results Kirsty Holloway - Senior Biomedical Scientist, Special Chemistry Section at CTMUHB inputting internal quality control results

6 LEADING EDGE - 2022-1 NHS Lanarkshire, to the east of Glasgow, is the third largest NHS Health Board in Scotland. It serves 655,000 people at the Hairmyres, Wishaw and Monklands Hospitals. Faecal calprotectin testing for the diagnosis and monitoring of inflammatory bowel diseases is conducted at the Monklands Hospital. Jacqui McGuire and Neil Syme, Consultant Clinical Biochemists from the Biochemistry Department at Monklands explain how their testing has evolved over recent years. “We perform around 400 faecal calprotectin tests a month across NHS Lanarkshire. Initially, when we first introduced the assay we used the BÜHLMANN fCAL® ELISA and CALEX extraction device, running the assays on a Dynex DS2 ELISA processor. As the volume of tests increased we switched to the BÜHLMANN fCAL® turbo assay on our Roche platform, in the spring of 2021. Since we were already using the CALEX® extraction method, this transferred to the turbo assays, retaining consistency and benefiting from the much easier work flow with the turbo method. Challenges of the Pandemic With the onset of COVID we were faced with a number of challenges to our testing processes. With concern regarding the risk of infection from stool samples, we didn’t have adequate access to bio-safety cabinets to handle our patient samples for the extraction process. The only way we could continue the service was if the patients could take their own samples directly in the CALEX devices. So, we implemented a process to outsource the calprotectin pre-analytical sample collection and preparation to the patients at home. We don’t offer faecal calprotectin in a primary care setting, so samples tend to just be from secondary care for monitoring purposes. We had discussions with the clinical team and recognised that the CALEX direct sample collection process is really very similar to that for the faecal immunochemical test (FIT) sample pickers used for bowel cancer screening and symptomatic testing. Since patients currently do this themselves very successfully, there was no resistance to rolling out a similar format for calprotectin testing. CALEX Stability The only real issue we had was the stability of the CALEX tubes when stored at ambient temperature, because the clinic doesn’t have enough capacity to store them in the fridge. When the process was initially established, the information we had was that the CALEX was stable at ambient for 3 months. So, we add an expiry date label to the tubes when they are issued to the clinic, so that this can be monitored on their return. The clinic are dispensing the CALEX devices and a specific instructions for use (IFU) document is supplied to the patients when a test is required. In the main this is by post but if the patient is coming into clinic for a face to face appointment, then they are being issued with the CALEX then. We ask for the patient demographic label to be applied to the tube when it is sent out and we re-label with a barcode when they are returned. Going forward this will be replaced by an ordercoms label when that is implemented. Once the sample has been collected the patients drop the CALEX back at their GP and it is brought to Wishaw Hospital to be sorted and separated from all the other samples, before being sent across to the Monklands Hospital. The CALEX tubes are checked for the ambient expiry date, and the level of buffer in the tubes, stored in the fridge and batches of tests are then run two to three times a week. Outsourcing Calprotectin Stool Pre-analytics to the Patient’s Home Jacqui McGuire and Neil Syme, Consultant Clinical Biochemists, Department of Biochemistry, Monklands Hospital

www.alphalabs.co.uk 7 The BÜHLMANN CALEX® Cap is the first and only stool extraction device certified for safe air and land transportation according to IATA 650 (UN3373) regulations. This allows the option to outsource pre-analytics to the patients’ homes, keeping stool samples away from the laboratory. Their small amount of sample is sealed in the CALEX and can be mailed directly to the laboratory or clinic. By getting the patient to use the CALEX to collect their sample at home, it is fully extracted and ready for calprotectin testing on arrival, using the BÜHLMANN Quantum Blue POCT assay or the ELISA or fCAL turbo laboratory assays. The same sample can also be tested for pancreatic elastase testing using the BÜHLMANN fPELA® turbo assay. CALEX is the same extraction device used in the laboratory setting. The optimised dilution of stool sample yields maximum extraction efficiency while offering stability of the calprotectin (7 days at room temperature) and p-elastase (7 days at room temperature) extracts. This convenient solution increases safety for laboratories and revolutionizes speed, efficiency and cost savings in the stool testing workflow. To help faciliate the logistics the BÜHLMANN CALEX® Cap Collection Set is specifically designed to simplify sample handling by patients. It provides convenient, hygienic and safe sample collection for the patient and provides a quality, ready extracted sample for analysis in the clinic. Testing Compliance In terms of patient compliance in using the CALEX to directly collect their faecal sample for calprotectin testing, it has been very good at around 90%. This is actually significantly better than we get for the FIT. The calprotectin test requests we get are from secondary care and so a lot of it is repeat testing for monitoring. So, the patients are more engaged than with the FIT which is usually a one off. We don’t seem to see much spoilage of samples with the CALEX (overloaded, no buffer, not labelled) probably <5%. We see a lot more spoilage with the FIT pickers but again that is probably for the same reasons of repeat users verses naïve users. Our compliance level is really good – a retrospective audit from the last six months showed that we did 500 samples per month with a return rate of 95%. Of the samples that were returned only 6% were unable to be tested. The implementation of the patient preparing the CALEX has certainly streamlined the laboratory workflow. It has freed up the space we used to do the extractions in and staff resource. There are discussions around opening the service to primary care and if this does go ahead then having the CALEX sent in ready prepared certainly lessens the impact on the laboratory from the increased workload. Having the samples arrive at the laboratory already in the CALEX has also helped in sample reception. Previously samples arrived in a universal tube and then the reception team needed to determine if it was for microbiology or biochemistry. Having the sample in the CALEX makes it immediately clear that the test is for calprotectin. Enabling the patients to prepare the CALEX themselves has saved us plenty of time in the laboratory and we would certainly recommend that other hospitals investigate how to make this work for them. It is worth noting that the ambient stability of CALEX is due to be extended later this year to at least 12 months, which will help with logistics.” For more information, visit our calprotectin website calprotectin.co.uk/calex Analysis of CALEX Tubes Returned July-Dec 2021 For more information on CALEX and to purchase please visit our website alphalabs.co.uk/calex 94% Samples analysed 3% Unlabelled 2% Low fluid level 1% Other 95% Return rate Ready To Use Samples UN3373 Compliant CALEX® Cap Collection Set for Faecal Extraction The kit contains: ✓ Instructions for use ✓ 1 X CALEX Cap ✓ 2 x Sample collection sheets ✓ 1 x Label for the CALEX ✓ 1 x Plastic bag

8 LEADING EDGE - 2022-1 In recent years we have all become more aware of the problems plastic causes to our environment and the need to massively reduce the amount of plastic waste we create. It is estimated that since the 1950s, humans have produced over 8.3 billion tons of plastic. Public concern for the extent of the problem of plastic waste has only been raised in more recent years, through documentaries such as David Attenborough’s Blue Planet or by activists such as Greta Thunberg. The British Government has launched the 25 Year Environment Plan which has pledged to eliminate all avoidable plastic waste by 2042. This will include the abolishment of plastic straws, carrier bags and food packaging. Plastic in Healthcare Unfortunately, much of the single use plastic in healthcare is seemingly unavoidable, with a huge 25% of the waste generated by hospitals being plastic. The use of plastic gloves and masks in hospitals are integral to protect healthcare workers from disease. Plastic is an extremely desirable material for hospitals and other healthcare environments due to it being low cost, very easily processed, very lightweight and able to be sterilised very easily. Plastic can even be modified to have a bacteriaresistant coating to help protect workers. While it is clear nobody can argue that safely disposing of hazardous PPE or biohazardous samples is an essential use of plastic, only 15% of healthcare waste is classed as “hazardous”; infectious, radioactive or toxic. The remaining 85% is similar to the plastic waste generated at home, which is where a reduction could be realised. In a typical operating theatre, there will be vast quantities of “blue wrap” used to place sterile equipment on or inside, which could easily be replaced by a sterilisable container. Surgeons also often use small resealable disposable plastic bags to keep their sterilised equipment inside, and it has been suggested these could be replaced by reusable steam sterilisation pouches such as those created by EnviroPouch®. Plastic gloves are another example, where in some cases are used unnecessarily. As stated by the Sustainable Development Unit for England’s National Health Service, there was a time when nurses at London’s Great Ormond Street hospital realised that healthcare professionals were choosing to use non-surgical gloves instead of washing their hands when performing tasks such as moving beds or bathing babies. When nurses started to remind staff that the gloves were not intended for these purposes, glove usage went down. The hospital was able to cut its use of plastic gloves, saving 21 tonnes of plastic and £90,000 as a result. There are many uses in healthcare, for which plastic is currently the best option at our disposal. Whilst it is highly unlikely that hospitals will ever be able to eliminate plastic waste due to the necessity for containing biohazardous waste material, there are certainly still ways to reduce usage in certain areas. Home-Testing Kits During the pandemic the use of home testing kits has become common place in across the nation. It is estimated that the UK is currently testing over 580, 000 people per day and over 4 million people per week. With this much single use plastic needing to be disposed of, and some of it incinerated, the only way to cut back on this is to make the plastic packaging as small as possible within the regulatory guidelines, which most test providers aren’t currently doing. UN3373 Sample Transport Requirements When transporting any diagnostic samples, whether blood, urine, faeces or swabs, from the patient to the laboratory for testing, the specimens must be packaged in accordance with the UN3373 Biological Substance, Category B regulations. These are a legal requirement designed to protect personnel from any exposure to potentially infectious samples during their transit. Failure to comply to the packaging requirements can lead to prosecution. UN3373 compliance requires a three-layer packaging system consisting of the primary vessel holding the sample (blood Vacutainer® Universal container, swab transport tube etc.). This must be enclosed in a secondary packaging solution that separates all vials and includes absorbent material that could soak up the entire contents of the primary container in event of its compromise. If the primary container is not 95kPa certified, then the secondary package must be. Finally, a rigid outer container is required which is marked with the UN3373 logo. Reducing the Volume of Single Use Plastic in Healthcare with the Award Winning ShuttlePouch™ Biohazard Transport Solution In just one week in May 2021, there were a total of 1,794,634 coronavirus PCR tests performed. Using ShuttlePouch™ as a packaging solution instead of competing products would use the equivalent amount of plastic of only 484,500 coronavirus PCR tests. On average, ShuttlePouch™ has a 73% reduction in plastic when compared to three direct competitors equivalent products. Statistics provided by Shuttlepac

www.alphalabs.co.uk 9 Reduce the Plastic Working with industry experts, the team at shuttlepac identified the many pain points plaguing the healthcare industry regarding the use of conventional 95kPa biohazard bags, including the massive plastic wastage. As a result, the reduction of plastic, as well as creating the highest quality product, is at the forefront of every single one of their designs. Commonly used biohazard bags that are traditionally used for secondary packaging are often unnecessarily large to hold the small vials within them. Could you imagine shopping for a few groceries and packing them in FOUR plastic bags instead of one? Yet this is the normalised practice within the healthcare industry! Unnecessarily large plastic bags dominate biohazard transport packaging. However, the ShuttlePouch™ can reduce plastic by up to 73%, and the figures don’t lie! Shuttlepac is championing the reduction of plastic in biological sample secondary packaging with the development of the UN3373 compliant ShuttlePouch™, a small pouch designed for individual tubes. ShuttlePouch™ is the best in show when it comes to reducing plastic wastage and providing secure secondary transport for biological material. Indeed, it recently won an award for innovative packaging - Flexible Plastic Pack of the Year, at the 2021 UK Packaging Awards. With up to 83% reduction in plastic material (average of 73% less across the range of standard biohazard bags), swapping to the ShuttlePouch™ has a noticeably positive environmental impact. This is especially true for the large number of home-test kits that are now in routine use. With the effects of the pandemic still in full swing, it is estimated that the UK is currently testing over 4 million people per week. With this much single use plastic needing to be disposed of, and some of it incinerated, the only way to cut back on this is to make the plastic packaging as small as possible within the regulatory guidelines, which the majority of test providers aren’t currently doing. Shuttlepac is the first in the industry to prioritise the reduction in plastic usage, and our overall environmental impact. Now is the time to move into the modern age by employing the state-of-the-art shuttlepac packaging solutions for biohazard transport! The reduction of plastic and production of the highest quality product is at the forefront of every shuttlepac design. The UN3373 compliant specimen transport solution, the ShuttlePouch™ addresses the issue of excessive plastic for secondary packaging of sample tubes by drastically reducing the size of the pouch to that more suitable for individual tubes. The 73% reduction in plastic usage means that, especially when it comes to home-test kits, swapping to the ShuttlePouch™ would have a noticeably positive environmental impact. Our thanks to Sandra Evans at shuttlepac for her contribution to this article. The ShuttlePouch™ range of leak proof pouches is designed to carry individual 95kPa pressure differential certified blood or urine specimen tubes (or any similar sized specimen tube). They include absorbent material already inside the pouch for convenient compliance to UN3373 packaging requirements. The pouches also feature a transparent front so the tube and label are clearly visible. An easy to open tear area facilitates processing when the samples arrive at the lab. The ShuttlePouch™ range is exclusive to Alpha Laboratories in the UK and Ireland, and provides a powerful, cost effective solution to the clinical and diagnostic market. Each leak proof bio-pouch is printed with easy-to-follow instructions showing how to pack and seal the specimen tube. Simply add a rigid outer packaging box for a complete and compliant UN3373 solution. In addition, the 95kPa pressure differential compliant ShuttlePouch™ is certified for transport by air (IATA). With all the features described above, they can be used with any leak free tube for transport by road or air. ShuttlePouch™ addresses the needs of customers, radically improving the user experience and reducing the cost of packing and shipping sample tubes compared with using conventional methods. Award Winning ShuttlePouch Cost Effective, User Friendly & UN3373 Compliant For more information on ShuttlePouch visit our website alphalabs.co.uk/ shuttlepouch Alpha Laboratories Ltd. is the exclusive partner for shuttlepac in the UK and Ireland. Find out more at www.UN3373.co.uk Size comparison between ShuttlePouch and competitor products

10 LEADING EDGE - 2022-1 New Presentation Format for UK NEQAS BÜHLMANN has been the market leading provider of faecal calprotectin assays in the UK for over 10 years, holding a significant portion of the market share, as recorded on the National External Quality Assurance Scheme (NEQAS). The BÜHLMANN results are split across the two main laboratory assays: fCAL ELISA and fCAL turbo assays. There is also some contribution from the IBDoc patient self-test assay. The current report format shows the data split out by method with 20 participants for fCAL ELISA, 26 participants for fCAL turbo and one participant for IBDoc in November 2021. The BÜHLMANN fCAL® turbo assay allows very rapid and flexible random access use, as well as being the ideal solution for high throughput applications in the routine laboratory. With it’s successful roll out over the last few years there are now 26 routine users on the UK NEQAS. These cover all the main clinical chemistry analyser systems including Abbott, Beckman, Roche and Siemens including all the various different models they have. More Detailed Reporting by Test Platform As part of some wider discussions with the Birmingham Quality UK NEQAS team (Finlay MacKenzie, Rachel Marrington and Martin Roch), it was thought to be a good idea to give their participants some additional information by asking on what platform fCAL turbo assays are being performed. This will allow fCAL turbo results to be broken down, and means provided, at the manufacturer level. Depending on the numbers of users for a manufacturer, it may be possible to further breakdown by analyser/platform in due course. Their USP Rainbow Trout Plot of interpretations versus concentration for each method will remain at the overall fCAL turbo level. Existing participants in their Scheme will be aware that the fCAL turbo is currently listed as a single method. For more information, visit the Birmingham Quality website: birminghamquality.org.uk Upcoming Events The Alpha Laboratories team is excited to be at the following Live UK Conferences & Exhibitions Clinical and Laboratory Haemostasis 2022 7-8 June | Stand 11 Sheffield Hallam University City Campus UK NEQAS for Blood Coagulation Annual Scientific Meeting. Come and talk to us about our range of high quality equipment, reagents and speciality products from our partners in haemostasis, including the new Factor VIII tests and reagents from Precision Biologic. BSG Live 2022 21-23 June | Stand A6 The International Convention Centre (ICC), Birmingham With a long tradition in providing diagnostics for digestive health management, Alpha Laboratories invites BSG visitors to our stand to discuss our innovative products that support these patient-pathways, including calprotectin, FIT, faecal elastase, anti-TNFα monitoring, allergy and microbial infections. BSMT 37th Annual Microbiology Conference 19 July Royal Air Force Museum, Hendon The Genomic & Microbiology Revolution: In Technology we Trust? We partner with leading manufacturers worldwide to provide innovative, high quality products that help improve the speed and accuracy of disease diagnosis so that effective treatment can be initiated speedily.

www.alphalabs.co.uk 11 Sepsis is a clinical syndrome caused by the body’s immune and coagulation systems being switched on by the presence of an infection - bacterial, viral, or fungal. Severe sepsis is defined as: Organ dysfunction Tissue hypoperfusion Sepsis Septic shock is a life-threatening condition that is characterised by: Low blood pressure despite adequate fluid replacement Organ dysfunction Sepsis The UK Sepsis Trust estimates that 37,000 people die from sepsis in the UK every year, with the most common causes of severe sepsis in adults being pneumonia and bowel perforation. The current definitions of sepsis and severe sepsis were established in critical care and paediatric critical care, which does not simply translate into diagnostic pathways for initial diagnosis and management since sepsis presentation can vary from patient to patient. Whilst early treatment of sepsis is associated with improved outcomes, it is clinically challenging to diagnose sepsis, especially in those who are critically ill. This means that sepsis can rapidly progress to organ dysfunction and death despite immediate and aggressive medical therapies. Current standard practice varies on the clinical experience of the physician or practitioner making the initial assessment. Identification relies on non-specific physiological criteria and culture-based pathogen detection. Due to the broad-spectrum indications, such as tachycardia, fever, chills, rash and an increase in inflammatory markers such as CRP, there can be delays in diagnosis and treatment, as well as misuse and overuse of antibiotics. Blood culture analysis is currently the gold standard for the identification of bacteria or fungi that cause infection. However, this method is slow and it can take several days to obtain blood culture results. Therefore, this method cannot significantly influence the initial management of patients. There are also issues with the detection of microbes in the sample and false negatives results due to contamination of the sample. Antibiotic Resistance This leads to patients receiving prolonged exposure to broad-spectrum antibiotics, which leads to the increase in bacterial antibiotic resistance. There is therefore a need for rapid, broad-based detection of pathogens causing the infection. Molecular Diagnostics Molecular diagnostics is defined as the detection of genomic variants, aiming to facilitate detection, diagnosis, subclassification, prognosis, and monitoring response to therapy. Panel-based molecular diagnostic assays are now available for direct testing of positive blood culture bottles (BCBs), leading to more timely results than conventional blood culture analysis. Faster identification and resistance characterisation of pathogens may lead to: Earlier administration of directed antimicrobial therapy Earlier de-escalation of broad-spectrum agents Potential for better outcomes Fewer antibiotic-associated adversities Less emergence of antimicrobial-resistant organisms Trials involving rapid multiplex PCR (rmPCR) based blood culture identification, such as Banerjee et al (2015), illustrate that the use of rmPCR can reduce the time to diagnosis and can optimise antibiotic prescribing for bloodstream infections. BCID2 Aids Early Bacterial Identification BioFire® FilmArray® Blood Culture Identification 2 (BCID2) Panels aid in the early identification and treatment of sepsis. With 43 targets, the BCID2 Panel detects pathogens and antimicrobial resistance genes directly from positive blood cultures, to shorten the time to optimal treatment.  The Clinical Challenges of Sepsis Emerging Technologies for Molecular Diagnostics First-of-its-kind quality control designed to meet the standards for verifying the entire analytical process of BioFire BCID2 sepsis assays from sample lysis to result reporting Simultaneously tests a single positive blood culture sample to giving results for 33 different organisms and organism groups that cause bloodstream infections and 10 antimicrobial resistance genes – one of the largest testing panels currently on the market Cost savings – MDx-Chex for BCID2 only uses 2 BioFire BCID2 panel pouches to deliver complete target coverage ISO15189 compliance - Can be used as a 3rd party quality control. Routine use of MDx-Chex for BCID2 as a full process quality control can help identify variations in the test system that can lead to incorrect results Allows for continued verification to ensure accurate Rapid Multiplex PCR–Based Blood Culture Identification for sepsis Contains stabilised blood components, blood culture media components, and inactivated micro-organisms resulting in a full-process, cellular-based control for the BioFire BCID2 Panel Use of full-process cellular controls evaluates the entire analytical process: sample lysis, nucleic acid isolation and purification, amplification, detection, and analysis, as well as the impact of PCR inhibitors and pre-analytical variables Quality control for BioFire® FilmArray 2.0® and FilmArray® Torch systems Storage conditions - 2 C to 25 C MDx-Chex™ Control for BCID2 Find out more and view the best practice video here: alphalabs.co.uk/mdx-chex

12 LEADING EDGE - 2022-1 Some traditional assays for trace metals include a pre-treatment step to deproteinise samples prior to analysis. Sentinel Diagnostics offer assays for zinc, copper and iron that eliminate the need to pre-treat samples this way improving workflow. Zinc Use with Serum, plasma or seminal fluid Measuring range 5-2000µg/dL Standard included On board stability 30 days No deproteinisation step Direct Colorimetric Assay NIST Standardisation Choice of kit sizes Improving Workflow of Trace Metals Zinc, Copper and Iron - Direct Colorimetric Assays Without a Deproteinisation Step For more information, visit our website: www.alphalabs.co.uk Also available: Magnesium Deproteinisation step required Use with Serum, plasma or urine Measuring range 0.04-10 mg/dL On board stability 30 days Ready to use liquid reagent Use with Clin Chem Calibrator Direct Colorimetric Assay NIST Standardisation Copper Use with Serum or plasma Measuring range 3-500µg/dL Standard included On board stability 45 days No deproteinisation step Direct Colorimetric Assay NIST Standardisation Copper for Urine Measuring range 3-20µg/dL Standard included No deproteinisation step Direct Colorimetric Assay NIST Standardisation Iron Use with Serum or plasma Measuring range 5-1000µg/dL On board stability 30 days Ready to use liquid reagents No deproteinisation step Direct Colorimetric Assay Use with Clin Chem Calibrator NIST Standardisation

www.alphalabs.co.uk 13 If you are running the one-stage activated partial thromboplastin time (APTT) method to help manage your haemophilia A patients, the new CRYOcheck™ Factor VIII deficient plasma with Von Willebrand Factor (VWF), from Precision Biologic, could improve your assay performance. It is currently the only commercially available manufactured Factor VIII deficient plasma that compares to using congenital factor VIII deficient plasma. Since access to congenital FVIII deficient plasma is limited and has high donor variability and small pool sizes, this newly available product provides enhanced convenience and increased confidence in testing results. CRYOcheck™ Factor VIII deficient plasma with Von Willebrand Factor (VWF) is for clinical laboratory use as a deficient substrate, in the one-stage activated partial thromboplastin time (APTT) method. It is used to quantitatively identify Factor VIII (FVIII) deficiency in 3.2% citrated human plasma, as an aid in the management of haemophilia A, for patients aged 2 years and above. The product has been manufactured from platelet-poor plasma that is screened negative for all FDA-required tests. It has been immunodepleted of FVIII and then purified VWF is reintroduced to normal levels. FVIII has been assayed at less than 1% normal antigen and activity levels, with VWF antigen and activity levels at >50%. The plasma is buffered and frozen, with the frozen format eliminating reconstitution errors and a 24-hour stability once thawed if refrigerated at 2 C - 8 C in the original capped vial. CRYOcheck™ Factor VIII deficient plasma with VWF has the highest proportion of active VWF and lowest amount of inactive FVIII antigen, making it most comparable to congenital deficient plasma. Key benefits: Convenient frozen format – no reconstitution FVIII antigen level < 1% Contains normal levels of VWF activity and VWF antigen VWF activity and antigen levels are available for every lot Screened negative for the presence of FVIII inhibitors 24-hour stability once thawed, on-board the analyser or when maintained at 2 C to 8 C Source plasmas are screened negative for all FDA-required tests FVIII Activity (OSC) <1% FVIII Antigen <1% VWF Activity >60% VWF Antigen ~100% Precision Biologic FVIII deficient plasma (+VWF) Yes Yes Yes Yes APTT Testing Results Enhanced Convenience and Increased Confidence See our full range of products to support Factor VIII testing and order online at: alphalabs.co.uk/facviii Factor VIII Deficient Plasma with VWF

14 LEADING EDGE - 2022-1 If you have recently made some changes and are working towards a more sustainable home or workplace, we’d love to hear from you! Send us your story and photographs to marketing@alphalabs.co.uk or tweet @alphalabs, for your chance to be showcased in our next Sustainability Snapshot. For every published story, choose one of our amazing free green goodies to support your continued green efforts. Share Your Story and we’ll send you some green goodies 64 Pen-y-Turnpike Wood 106 Home Farm 20 Uffmoor Wood 86 Castle Camps For many years Alpha Laboratories has been involved with a number of projects to support environmentally friendly practices, and now we’re taking it one step further! Our recently formed Sustainability Working Group is looking at ways to further improve our green credentials, as well as supporting the local community, and working with customers and suppliers to help the whole supply chain to become as environmentally friendly as possible. Here we set out some of the goals for 2022, and reflect on the activities we’re already committed to. Hopefully these plans will provide some inspiration to you, and your team, on how you can join in and help to create a more sustainable world. Keep up to date with our progress in every edition of our publications Leading Edge and LabVantage and on our website: alphalabs.co.uk/sustainability Sustainability Spotlight: LaboraTree It was way back in 2009 that the first seed of the Alpha Laboratories’ tree planting scheme, LaboraTree, was sown. Thanks to the dedicated LaboraTree members in laboratories throughout the UK, over 2,500 trees have now been planted across the country and are helping make a positive contribution to our environment. The trees planted by our members have helped absorb CO2, improve air quality, and support biodiversity and local wildlife. Fastrak® tips are going even further to support sustainability: the packaging is made from 95% renewable materials which include a compostable base made from a non-petroleum resin and the outer packaging is printed using vegetablebased inks. Compact and easy to store; the Fastrak® refill system helps you to maximise storage space in the laboratory, whilst reducing your carbon-footprint. Sustainability Snapshot Growing Our Efforts in Environmentally Friendly Practices Pictured: Seedballs, Hedgehog House, Bee House, Bird House. Items may vary. To date, we have planted over 2000 trees together through the LaboraTree Scheme The woods in dark green are now full thanks in part to the trees we’ve planted. The light green are the places we continue to plant in. 52 Londonthorpe Wood 38 Old Wood 43 Theydon Bois 64 Birdwell Wood 171 Stanley Wood 247 Brede High Wood 266 Glen Finglas 117 Priory Grove 6 Spud Wood 332 Penguin Wood 56 Valley Park 161 Gault Wood 53 Fordham Hall 19 Avon Valley 14 Marden Park 15 Lineover Wood 37 Dutton Park 228 Watkins Wood 60 Casehill Meadows

www.alphalabs.co.uk 15  Set up the Alpha Aspire Barton Peveril Sixth Form Programme: delivering presentations to help support science students  Provided Barton Peveril students with much needed resources including laptops and safety equipment  Working with Shakespeare Infant School to develop outdoor learning areas and sensory gardens  Working with St. Francis Primary School to build an allotment  Use environmentally friendly stationery  LED lighting in the offices and warehouse  Re-using packaging materials or using eco-friendly alternatives to cut down on waste materials  Expanding our recycling efforts throughout the building for a wide range of materials  The ‘Big Dig’ team planted rowan trees and a thorn hedge border to enclose the green space outside HQ to encourage nesting birds and provide wildlife shelter  Built a raised plant bed to grow a range of pollinator-friendly plants  Built a “bug hotel” to support local ecosystems Supporting Our Local Communities Actions at Alpha Laboratories HQ Future Project Roots  Planning litter picking and beach clean events for Alpha staff and volunteers  Working towards 100% renewable energy through installation of solar panels at Alpha HQ  Reviewing our Supply Chain for wastage hot-spots and minimising them  Further presentations and equipment supplies to Barton Peveril Students to support their studies  Help maintain the gardens at Shakespeare Infant School in Hampshire  Supplying school equipment (such as microscopes) to support the study of the garden and scientific curiosity

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.calprotectin.co.uk Turbo Charge Your Faecal Testing The BÜHLMANN fCAL® turbo and fPELA assays will revolutionise your faecal calprotectin and elastase testing with a streamlined workflow.  Same CALEX® extraction for both assays: - One extraction two tests  CALEX® can be given to patients for sample collection - Ambient, fridge and freezer stability for a flexible return to laboratory workflow  Wide assay range provides valuable clinical insight and keeps dilutions to a minimum - Calprotectin: 20 – 2000µg/g (autodilute to 8000µg/g) - Elastase: 10 - 500µg/g  Time to first result is 10 minutes, with further results every few seconds  Protocols available for most clinical chemistry analysers - Including Abbott, Beckman, Roche, Siemens as well as stand-alone options  Calibrators, controls and reagents are all in a stable, ready to use format and they don’t need to be lot matched Contact Alpha Laboratories today to find out more.